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65f0fbd4e9ebbb4db995a117 | 10.26434/chemrxiv-2024-9sdv6 | B(C6F5)3-Catalyzed Formal (n+3) (n = 5,6) Cycloaddition of Bicyclo[1.1.0]butanes to Medium Bicyclo[n.1.1]alkanes | Herein, a B(C6F5)3-catalyzed formal (n+3) (n = 5,6) cycloaddition of bicyclo[1.1.0]butanes (BCBs) with imidazolidines/hexahydropyrimidines is described. The reaction provides a modular, atom-economical and efficient strategy to two libraries of synthetically challenging medium-bridged rings, 2,5-diazabicyclo[5.1.1]nonanes and 2,6-diazabicyclo[6.1.1]decanes, in moderate to excellent yields. This reaction also features simple operation, mild reaction conditions and broad substrate scope. A scale-up experiment and various synthetic transformations of products further highlight the synthetic utility. Control experiments support that the reaction mechanism involves a nucleophilic addition of imidazolidines/hexahydropyrimidines to B(C6F5)3-activated BCBs, succeeded by an intramolecular cyclization. As we know, this methodology represents the first high order (n+3) (n > 3) cycloaddition of BCBs to saturated bicyclo[n.1.1]alkanes. We anticipate that this report will promote the exploration of BCB-based high order cycloaddition chemistry to access diverse challenging medium-bridged rings. | Liangliang Yang; Haiyang Wang; Ming Lang; Jian Wang; Shiyong Peng | Organic Chemistry; Catalysis; Organic Synthesis and Reactions; Acid Catalysis | CC BY 4.0 | CHEMRXIV | 2024-03-15 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/65f0fbd4e9ebbb4db995a117/original/b-c6f5-3-catalyzed-formal-n-3-n-5-6-cycloaddition-of-bicyclo-1-1-0-butanes-to-medium-bicyclo-n-1-1-alkanes.pdf |
674eb51af9980725cfe03f23 | 10.26434/chemrxiv-2024-hnsv9 | Electrochemical Conversion of Carboxylic Acids to Terminal Alkenes Enabled by Dialkyl Phosphate Electrolyte | Electrochemical regioselective conversion of carboxylic acids to terminal alkenes through dehydrogenative decarboxylation was developed. Mechanistic studies suggested that the reaction proceeds through oxidative decarboxylation of carboxylic acids to give the corresponding primary carbocation intermediates followed by deprotonation. It was implied that when using a supporting electrolyte with high donor number anion, such as dialkyl phosphate, the isomerization of the primary carbocation intermediates was suppressed to cause higher selectivity to terminal alkenes. | Tasuku Ito; Xiongjie Jin; Kyoko Nozaki | Organic Chemistry; Organic Synthesis and Reactions | CC BY NC ND 4.0 | CHEMRXIV | 2024-12-05 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/674eb51af9980725cfe03f23/original/electrochemical-conversion-of-carboxylic-acids-to-terminal-alkenes-enabled-by-dialkyl-phosphate-electrolyte.pdf |
60c73d0f469df43f15f42680 | 10.26434/chemrxiv.5435935.v1 | Fast and Accurate Prediction of the Regioselectivity of Electrophilic Aromatic Substitution Reactions | While computational prediction of chemical reactivity is possible it usually requires expert knowledge and there are relatively few computational tools that can be used by a bench chemist to help guide synthesis. The RegioSQM method for predicting the regioselectivity of electrophilic aromatic substitution reactions of heteroaromatic systems is presented in this paper. RegioSQM protonates all aromatic C-H carbon atoms and identifies those with the lowest free energies in chloroform using the PM3 semiempirical method as the most nucleophilic center. These positions are found to correlate qualitatively with the regiochemical outcome in a retrospective analysis of 96% of more than 525 literature examples of electrophilic aromatic halogenation reactions. The method is automated and requires only a SMILES string of the molecule of interest, which can easily be generated using chemical drawing programs such as ChemDraw. The computational cost is 1-10 minutes per molecule depending on size, using relatively modest computational resources and the method is freely available via a web server at regiosqm.org. RegioSQM should therefore be of practical use in the planning of organic synthesis. | Jimmy Kromann; Jan H. Jensen; Monika Kruszyk; Mikkel Jessing; Morten Jørgensen | Computational Chemistry and Modeling | CC BY 4.0 | CHEMRXIV | 2017-09-28 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/60c73d0f469df43f15f42680/original/fast-and-accurate-prediction-of-the-regioselectivity-of-electrophilic-aromatic-substitution-reactions.pdf |
62bb4ede52acb75b3e76c088 | 10.26434/chemrxiv-2022-mkfzd | Role of electronic polarization in the primary charge-transfer states of the purple bacteria reaction center: A polarizable QM/MM study with the integral-exact direct reaction field method | A hybrid QM/MM study with the integral-exact direct reaction field (IEDRF) polarizable embedding scheme developed in the companion paper is performed on the purple bacteria reaction center of Rhodobacter sphaeroides in order to investigate how polarization induced in the protein matrix helps to stabilize the primary charge-transfer state relative to the exciton states of the special pair. The protein environment is represented by point charges and induced dipoles that are coupled to the QM region via the integral-exact direct reaction field Hamiltonian, which can simultaneously describe differential solvation of multiple electronic states of different polarities.
Treating the special pair, $P=P_L P_M$, and one of the bacteriopheophytins ($H_L$ or $H_M$) quantum-mechanically, we compare excitation energies computed at the $\omega$PBEh time-dependent density functional theory level for charge-transfer states along the active and inactive branches. Thermal fluctuations on the electronic-state energies are included by extracting snapshots from a molecular dynamics trajectory. With IEDRF embedding, the reaction field induced in the protein matrix stabilizes long-range charge-transfer (CT) states by over 1.0 eV, shifting them below the exciton states. The protein environment favors charge separation along the active $L$ branch. With only electrostatic embedding, the CT states are found $>$0.5 eV above the exciton states, and asymmetry between the branches is diminished. The polarization in the protein is largely dictated by the secondary structure, with induced dipoles pointing along the axes of $\alpha$-helices. The relaxation of dipoles on the excited state provides similar stabilization of both branches, however the ground state polarization, captured by IEDRF, screens $P^+ H_L^-$ more than $P^+ H_M^-$ and is thus key to directing the CT towards the active branch. The different ground-state dielectric environment of the two branches is confirmed by computing relative local fields at key carbonyl probes. With IEDRF embedding, we find the local fields to be in near quantitative agreement with the interpretations of recent vibrational Stark-effect experiments, while the agreement is diminished for electrostatically embedded QM/MM calculations. These results caution against QM/MM calculations with electrostatic embedding alone, because CT states in a rigid, dense protein matrix are mostly stabilized by the fast electronic polarization of the surrounding medium. | Alexander Humeniuk; Amiel S. P. Paz; Yuquan Cao; William J. Glover | Theoretical and Computational Chemistry; Computational Chemistry and Modeling | CC BY NC 4.0 | CHEMRXIV | 2022-06-29 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/62bb4ede52acb75b3e76c088/original/role-of-electronic-polarization-in-the-primary-charge-transfer-states-of-the-purple-bacteria-reaction-center-a-polarizable-qm-mm-study-with-the-integral-exact-direct-reaction-field-method.pdf |
631f7b4b173b5d6644fa9d4e | 10.26434/chemrxiv-2022-mgwnm-v2 | Shining a Light on Photoresponsive Type III Porous Liquids | Porous materials are the subject of extensive research because of potential applications in areas such as gas adsorption and molecular separations. Until recently, most porous materials were solids, but there is now an emerging class of materials known as porous liquids. The incorporation of intrinsic porosity or cavities in a liquid can result in free-flowing materials that are capable of gas uptakes that are significantly higher than conventional non-porous liquids. A handful of porous liquids have also been investigated for gas separations. Until now, the release of gas from porous liquids has relied on molecular displacement (e.g., by adding small solvent molecules), pressure or temperature swings, or sonication. Here, we explore a new method of gas release that involves photoisomerisable porous liquids comprising a photoresponsive MOF dispersed in an ionic liquid. This results in the selective uptake of CO2 over CH4, and allows gas release to be controlled by using UV light. | Michael Brand; Nicola Rankin; Andrew Cooper; Rebecca Greenaway | Materials Chemistry | CC BY 4.0 | CHEMRXIV | 2022-09-13 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/631f7b4b173b5d6644fa9d4e/original/shining-a-light-on-photoresponsive-type-iii-porous-liquids.pdf |
6581aa1a9138d231610b0c44 | 10.26434/chemrxiv-2022-jvxj1-v2 | Chiral arylsulfinylamides: all-in-one reagents for visible light-mediated asymmetric alkene aminoarylations | Two- or one-electron mediated alkene aminoarylations represent straightforward approaches to assemble molecular complexity by the simultaneous formation of two contiguous Csp3-Csp2/Csp3-N stereocenters. While racemic versions have been extensively explored, asymmetric variants, especially those involving open-shell C-centered radical species, are much more limited both in number and scope. In this work, we describe enantioenriched arylsulfinylamides as all-in-one reagents for the efficient asymmetric, intermolecular aminoarylation of alkenes. Under mild photoredox conditions, Nitrogen addition of the arylsulfinylamide onto the double bond followed by 1,4-translocation of the aromatic ring produce the corresponding aminoarylation adducts in a single operation. The sulfinyl group acts here as a traceless chiral auxiliary and is eliminated in situ under the reaction conditions. Optically pure beta, beta-diarylethyl- and aryl-alpha, beta-ethylenediamines, prominent motifs in pharmaceuticals and bioactive natural products, are obtained with excellent levels of regio-, relative and absolute stereocontrol. | Cedric Hervieu; Mariia S. Kirillova; Yawen Hu; Sergio Cuesta-Galisteo; Estíbaliz Merino; Cristina Nevado | Organic Chemistry; Catalysis; Photocatalysis | CC BY NC 4.0 | CHEMRXIV | 2023-12-20 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/6581aa1a9138d231610b0c44/original/chiral-arylsulfinylamides-all-in-one-reagents-for-visible-light-mediated-asymmetric-alkene-aminoarylations.pdf |
60c749d4842e65a9eadb2de6 | 10.26434/chemrxiv.11749854.v2 | Enhancing a De Novo Enzyme Activity by Computationally-Focused, Ultra-Low-Throughput Sequence Screening | <div>
<div>
<div>
<p>Directed evolution has revolutionized protein engineering. Still, enzyme optimization by random
library screening remains a sluggish process, in large part due to futile probing of mutations that
are catalytically neutral and/or impair stability and folding. FuncLib (funclib-weizmann.ac.il) is a
novel automated computational procedure which uses phylogenetic analysis and Rosetta design to
rank enzyme variants with multiple mutations, on the basis of a stability metric. Here, we use it to
target the active site region of a minimalist-designed, de novo Kemp eliminase. The similarity
between the Michaelis complex and transition state for the enzymatic reaction makes this a
particularly challenging system to optimize. Yet, experimental screening of a very small number
of active-site, multi-point variants at the top of the predicted stability ranking leads to catalytic
efficiencies and turnover numbers (~2·104 M-1 s-1 and ~102 s-1) that compare well with modern
natural enzymes, and that approach the catalysis levels for the best Kemp eliminases derived from
extensive screening. This result illustrates the promise of FuncLib as a powerful tool with which
to speed up directed evolution, by guiding screening to regions of the sequence space that encode
stable and catalytically diverse enzymes. Empirical valence bond calculations reproduce the
experimental activation energies for the optimized eliminases to within ~2 kcal·mol-1 and indicate
that the improvements in activity are linked to better geometric preorganization of the active site.
This raises the possibility of further enhancing the stability-guidance of FuncLib by EVB-based
computational predictions of catalytic activity, as a generalized approach for computational
enzyme design.
</p>
</div>
</div>
</div> | Valeria A. Risso; Adrian Romero-Rivera; Luis I. Gutierrez-Rus; Mariano Ortega-Muñoz; Francisco Santoyo-Gonzalez; José A. Gavira; Jose Manuel Sanchez Ruiz; Shina Caroline
Lynn Kamerlin | Biocatalysis | CC BY 4.0 | CHEMRXIV | 2020-04-06 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/60c749d4842e65a9eadb2de6/original/enhancing-a-de-novo-enzyme-activity-by-computationally-focused-ultra-low-throughput-sequence-screening.pdf |
674877277be152b1d038b13d | 10.26434/chemrxiv-2024-9wbz4 | A platform for the development of highly red-shifted azobenzenes | Azobenzenes are versatile photoswitches that can be used to generate elaborate optical tools including photopharmaceuticals. However, the targeted application-guided design of new photoswitches with specific properties, such as the ability to use tissue-penetrating red light combined with defined thermal relaxation rates and stability towards biological reducing agents, remains challenging. We have developed synthetic protocols for derivatives of the dfdc (di-ortho-fluoro di-ortho-chloro) azobenzene scaffold with various chemical alterations in the para-/ortho-positions and performed an in-depth study into the effects of their structures on their photo-physical properties with an emphasis on the n → pi* absorption band using NMR, UV-vis and X-ray analysis. The data was used to establish and validate a computational approach that, among other parameters, allows to compute realistic UV-vis spectra by combining TD-DFT excited-state calculations from 6000 thermally accessible structures generated through ab-initio MD simulations while taking the high structural flexibility of ortho-substituted azobenzenes into account. With our platform, we added 15 new visible light-operated photoswitches to the toolbox for the development of optical devices that harbor relaxation rates across multiple orders of magnitude. We have identified several examples with stronger bathochromic shifts than the dfdc azobenzene lead structure and a high stability towards the biological reducing agent GSH, which is a prerequisite for in vivo applications. An intriguing example is dfdb (di-ortho-fluoro di-ortho-bromo) azobenzene which demonstrates accelerated photoswitching with deep red light at increased temperatures. Taken together, our combined experimental and computational study forms the foundation for the advanced in silico design and synthesis of new highly red-shifted azobenzene photoswitches. | Kyra Lützel; Henryk Laqua; Judit Katalin Szántó; Gökcen Savasci; Lars Allmendinger; Bilal Kicin; Vincent Ruf; Konstantin Karaghiosoff; Ahmed M. Ali; Christian Ochsenfeld; David B. Konrad | Theoretical and Computational Chemistry; Organic Chemistry | CC BY NC ND 4.0 | CHEMRXIV | 2024-11-29 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/674877277be152b1d038b13d/original/a-platform-for-the-development-of-highly-red-shifted-azobenzenes.pdf |
67a1ade46dde43c908889b25 | 10.26434/chemrxiv-2025-dxwrr | Synthesis of Selectively 13C/2H/15N-Labelled Arginine to Probe Protein Conformation and Interaction by NMR Spectroscopy | The charged arginine side chain is unique in determining many innate properties of proteins, contributing to stability and interaction surfaces, and directing allosteric regulation and enzymatic catalysis. NMR experiments can be used to reveal these processes at the molecular level, but it often requires selective insertion of carbon-13, nitrogen-15 and deuterium at defined atomic positions. We introduce a method to endow arginine residues with defined isotope patterns, combining synthetic organic chemistry and cell-based protein overexpression. The resulting proteins feature NMR active spin systems with optimized relaxation pathways leading to simplified NMR spectra with a sensitive response to changes in the chemical environment of the nuclei observed. | Darja Rohden; Giorgia Toscano; Paul Schanda; Roman Lichtenecker | Physical Chemistry; Organic Chemistry; Biophysical Chemistry | CC BY NC 4.0 | CHEMRXIV | 2025-02-05 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/67a1ade46dde43c908889b25/original/synthesis-of-selectively-13c-2h-15n-labelled-arginine-to-probe-protein-conformation-and-interaction-by-nmr-spectroscopy.pdf |
6626707a91aefa6ce1195724 | 10.26434/chemrxiv-2024-s18q5 | Nature-inspired radical pyridoxal-mediated C–C bond formation | Pyridoxal-5'-phosphate (PLP) and derivatives of this cofactor enable a plethora of reactions in both enzyme-mediated and free-in-solution transformations. With few exceptions in each category, such chemistry has predominantly involved two-electron processes. This sometimes poses a significant challenge for using PLP to build tetrasubstituted carbon centers, especially when the reaction is reversible. The ability to access radical pathways is paramount to broadening the scope of reactions catalyzed by this coenzyme. In this study, we demonstrate the ability to access a radical PLP-based intermediate and engage this radical intermediate in a number of C–C bond forming reactions. By selecting an appropriate oxidant, single-electron oxidation of the quinonoid intermediate can be achieved, which can subsequently be applied to C–C bond forming reactions. Through this radical reaction pathway, we synthesized a series of α-tertiary amino acids and esters to investigate the substrate scope and identify non-productive reaction pathways. Beyond the amino acid model system, we demonstrate that other classes of amine substrates can be applied in this reaction and that a range of small molecule reagents can serve as a coupling partner to the semiquinone radical. We anticipate that this versatile semiquinone radical species will be central to the development of a range of novel reactions. | Ye Wang; Sarah Champagne; Philipp Gemmel; Kevin Skinner; Paul Zimmerman; Alison Narayan | Organic Chemistry; Catalysis; Organic Synthesis and Reactions | CC BY NC ND 4.0 | CHEMRXIV | 2024-04-23 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/6626707a91aefa6ce1195724/original/nature-inspired-radical-pyridoxal-mediated-c-c-bond-formation.pdf |
6704f97d51558a15ef7c2e4c | 10.26434/chemrxiv-2024-06gt1 | A T-shaped, Open-Shell Cobalto-Germylene Demonstrating Dynamic Covalent Bond Activation | Reaction of chelating cationic germylene ligand [PhiPDippGe]+ (1; PhiPDipp = {[Ph2PCH2Si(iPr)2](Dipp)N}; Dipp = 2,6-iPr2C6H3) with the NHC-stabilised Co0 system [IPr·Co(η2-vtms)2] gives ready access to the first example of an open-shell metallo-germylene in T-shaped Co complex 2, in high yields. Complex 2 is formed through the formal oxidative addition of the germylene to Co, giving a unique route to this compound class. The Co centre in 2 bears a high-spin density of its single unpaired electron, corroborated by SQUID magnetometry, EPR spectroscopy, and quantum-chemical calcula-tions. Detailed analysis of the electronic structure of 2 establish the distinct nature of the germanium cobalt interaction as an electron-sharing covalent bond. Still, the formation of 2 is not trivial: shortening reaction times leads to the formation of three different fragments of this species (viz. 3, 4, and 5), which can be isolated and fully characterised; further, these quantitatively recombine over extended reaction times in forming 2. This is borne out by trapping of one additional species, namely cobalto-germylene complex 7, through the addition of a Lewis base to dissolved 2, highlighting the highly dynamic collection of species formed in solution from dissolved 2. | Annika Schulz; Myron Heinz; Max Holthausen; Terrance Hadlington | Inorganic Chemistry; Organometallic Chemistry; Bonding; Ligands (Organomet.); Transition Metal Complexes (Organomet.) | CC BY NC ND 4.0 | CHEMRXIV | 2024-10-09 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/6704f97d51558a15ef7c2e4c/original/a-t-shaped-open-shell-cobalto-germylene-demonstrating-dynamic-covalent-bond-activation.pdf |
61dd6f8ea160508af79d200e | 10.26434/chemrxiv-2022-pl3r8 | Non-Covalent Interactions Atlas Benchmark Data Sets 5: London Dispersion in an Extended Chemical Space | The Non-Covalent Interactions Atlas (www.nciatlas.org) has been extended with two data sets of benchmark interaction energies in complexes dominated by London dispersion. The D1200 data set of equilibrium geometries provides a thorough sampling of an extended chemical space, while the D442×10 set features dissociation curves for selected complexes. In total, they provide 5,178 new CCSD(T)/CBS data points of the highest quality. The new data have been combined with previous NCIA data sets in a comprehensive test of dispersion-corrected DFT methods, identifying the ones that achieve high accuracy in all types of non-covalent interactions in a broad chemical space. Additional tests of dispersion-corrected MP2 and semiempirical QM methods are also reported. | Jan Řezáč | Theoretical and Computational Chemistry; Computational Chemistry and Modeling; Chemoinformatics - Computational Chemistry | CC BY NC ND 4.0 | CHEMRXIV | 2022-01-12 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/61dd6f8ea160508af79d200e/original/non-covalent-interactions-atlas-benchmark-data-sets-5-london-dispersion-in-an-extended-chemical-space.pdf |
66e08e0151558a15ef9d26f6 | 10.26434/chemrxiv-2024-zvt26 | MORE-Q, Dataset for molecular olfactorial receptor engineering by quantum mechanics | We introduce the MORE-Q dataset, a quantum-mechanical (QM) dataset encompassing the structural and electronic data of non-covalent molecular sensors formed by combining 18 mucin-derived olfactorial receptors with 102 body odor volatilome (BOV) molecules. To have a better understanding of their intra- and inter-molecular interactions, we have performed accurate QM calculations in different stages of the sensor design and, accordingly, MORE-Q splits into three subsets: i) MORE-Q-G1: QM data of $18$ receptors and $102$ BOV molecules, ii) MORE-Q-G2: QM data of 23,838 BOV-receptor configurations, and iii) MORE-Q-G3: QM data of 1,836 BOV-receptor-graphene systems. Each subset involves geometries optimized using GFN2-xTB with D4 dispersion correction and up to 39 physicochemical properties, including global and local properties as well as binding features, all computed at the tightly converged PBE+D3 level of theory. By addressing BOV-receptor-graphene systems from a QM perspective, MORE-Q can serve as a benchmark dataset for state-of-the-art machine learning methods developed to predict binding features. This, in turn, can provide valuable insights for developing the next-generation mucin-derived olfactory receptor sensing devices. | Li Chen; Leonardo Rafael Medrano Sandonas; Philipp Traber; Arezoo Dianat; Nina Tverdokhleb; Mattan Hurevich; Shlomo Yitzchaik; Rafael Gutierrez; Alexander Croy; Gianaurelio Cuniberti | Theoretical and Computational Chemistry; Materials Science; Computational Chemistry and Modeling; Theory - Computational; Machine Learning | CC BY 4.0 | CHEMRXIV | 2024-09-11 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/66e08e0151558a15ef9d26f6/original/more-q-dataset-for-molecular-olfactorial-receptor-engineering-by-quantum-mechanics.pdf |
65f2b3379138d231616ed62a | 10.26434/chemrxiv-2024-rtx53-v2 | High-resolution 17O solid-state NMR as a unique probe
for investigating oxalate binding modes in materials:
The case study of calcium oxalate biominerals | Oxalate ligands are found in many classes of materials, including energy-storage materials and biominerals like hydrated calcium-oxalates. Determining their local environments at the atomic scale is thus paramount to establishing the structure and properties of numerous phases. Here, we show that high-resolution 17O solid-state NMR is a valuable asset for investigating the structure of crystalline oxalate systems. First, an efficient 17O-enrichment procedure of oxalate ligands is demonstrated using mechanochemical saponification. Then, the use of 17O-enriched oxalates for the synthesis of the biologically relevant calcium-oxalate monohydrate (COM) phase is presented, enabling the analysis of its structure and heat-induced phase transitions by high-resolution 17O solid-state NMR. NMR studies of the low-temperature COM form (LT-COM), using magnetic fields varying from 9.4 to 35.2 T, as well as 13C-17O MQ/D-RINEPT and 17O{1H} MQ/REDOR experiments, enabled the 8 inequivalent oxygen sites of the oxalate ligands to be resolved, with a tentative assignment proposed. Then, the structural changes occurring upon heat treatment of COM were followed by high-resolution 17O solid-state NMR, providing new insight into the structures of the high-temperature form (HT-COM) and anhydrous calcium oxalate alpha-phase (alpha-COA), including the presence of structural disorder in the latter case. Overall, this work highlights the ease associated with 17O-isotopic enrichment of oxalate oxygens, and how it enables the study of oxalate structures (including materials of biological relevance) at high-resolution via solid-state NMR, in the frame of “NMR-crystallography” investigations. | Ieva Goldberga; Ivan Hung; Vincent Sarou-Kanian; Christel Gervais; Zhehong Gan; Jessica Novák-Špačková ; Thomas-Xavier Métro; César Leroy; Dorothée Berthomieu; Arie van der Lee; Christian Bonhomme; Danielle Laurencin | Analytical Chemistry; Spectroscopy (Anal. Chem.); Materials Chemistry | CC BY NC ND 4.0 | CHEMRXIV | 2024-03-15 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/65f2b3379138d231616ed62a/original/high-resolution-17o-solid-state-nmr-as-a-unique-probe-for-investigating-oxalate-binding-modes-in-materials-the-case-study-of-calcium-oxalate-biominerals.pdf |
60c75545469df4450df45133 | 10.26434/chemrxiv.14050712.v1 | Attaching Strong Auxiliary Acceptor onto B-N-Containing Multiple Resonance Framework and Achieving Highly Efficient Electroluminescence with Ultrahigh Color Purity | <p>The development and enrichment of
organic materials with narrowband emission in longer wavelength region beyond
515 nm still remains a great challenge. Herein, a series of unique narrowband
green thermally activated delayed fluorescence (TADF) emitters has been
constructed based on a synthetic strategy by localized attachment of acceptor
onto B-N-containing multiple resonance (MR) framework. The precise modulation
of acceptor is an ingenious approach for achieving bathochromic shift and
narrowband emission, simultaneously. Furthermore, an important synthetic
methodology has been proposed to functionalize MR skeleton and generate a
universal building block, which can be utilized to construct multifarious TADF
materials with ultrahigh color purity through a simple one-step Suzuki coupling
reaction. The DtCzB-TPTRZ-based organic light-emitting diode (OLED) exhibits
pure green emission with Commission Internationale de L’Eclairage (CIE)
coordinates of (0.23, 0.68), and achieves remarkable maximum external quantum
efficiency (EQE) of 30.6% with low efficiency roll-off.</p> | Chenglong Li; Yue Wang; Yincai Xu; Zhiqaing Li; Jiaxuan Wang; Jianan Xue; Qingyang Wang; Xinliang Cai | Optical Materials | CC BY NC ND 4.0 | CHEMRXIV | 2021-03-09 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/60c75545469df4450df45133/original/attaching-strong-auxiliary-acceptor-onto-b-n-containing-multiple-resonance-framework-and-achieving-highly-efficient-electroluminescence-with-ultrahigh-color-purity.pdf |
6284b5a844bdd53592675638 | 10.26434/chemrxiv-2022-g58r5 | Sulfoximines in Medicinal Chemistry: Emerging Trends and Opportunities from the Drug Designer’s Perspective | Extension of the medicinal chemistry toolbox is in the vital interest of drug designers who are confronted with the task of finding molecular solutions for an ever-increasing biological target space. However, the diffusion of an innovation can be a lengthy process even within the drug discovery community which faces enormous pressure to formulate effective solutions for patients in a timely manner. Along these lines, it took almost 70 years before the use of the sulfoximine group reached a critical mass in medicinal chemistry. Even though interest in this versatile functional group has increased exponentially in recent years, there is ample room for further innovative applications. This minireview highlights emerging trends and opportunities for drug designers for the utilization of the sulfoximine group in medicinal chemistry, such as in the construction of complex molecules, proteolysis targeting chimeras (PROTACs), antibody–drug conjugates (ADCs) and novel warheads for covalent inhibition. | Ulrich Luecking | Biological and Medicinal Chemistry; Drug Discovery and Drug Delivery Systems | CC BY NC ND 4.0 | CHEMRXIV | 2022-05-18 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/6284b5a844bdd53592675638/original/sulfoximines-in-medicinal-chemistry-emerging-trends-and-opportunities-from-the-drug-designer-s-perspective.pdf |
66fc18da12ff75c3a10f6dab | 10.26434/chemrxiv-2024-m3v4m | A bright organic fluorophore for precise measurement of the relative quantum yield in the NIR-II window | Organic dyes with photoluminescence in the second near-infrared window (NIR-II, 1000–1700 nm) are essential in bioimaging and optoelectronic devices. Photoluminescence quantum yield (PLQY) is their important performance indicator. Integrating sphere technology is effective in determining the absolute PLQY. However, the low emission brightness of most NIR-II organic fluorophores results in unacceptable errors. Therefore, the most common method for determining the PLQY is a relative approach using photoluminescence spectrometers and a standard reference like IR-26. Although the relative method can obtain accurate PLQY ratios between the samples and references, the specific PLQY value of IR-26 is not clearly defined, which is reported to range from 0.05% to 0.50%. Such a deviation can cause significant errors in relative PLQY measurements. In this study, a bright organic fluorophore called TPE-BBT exhibits a high PLQY of 4.17% in THF, which can be accurately measured using a commercially available integrating sphere. Using TPE-BBT as a standard reference, we have determined the PLQY values of IR-26 in DCE to be 0.0301% and IR-1061 in DCM to be 0.193%. | Hanchen SHEN; Xinyan Zhu; Jianyu Zhang; Changhuo Xu; Jacky Lam; Ben Zhong Tang | Physical Chemistry; Materials Science; Analytical Chemistry; Photochemistry (Physical Chem.); Physical and Chemical Properties | CC BY 4.0 | CHEMRXIV | 2024-10-03 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/66fc18da12ff75c3a10f6dab/original/a-bright-organic-fluorophore-for-precise-measurement-of-the-relative-quantum-yield-in-the-nir-ii-window.pdf |
60c742d9702a9b08b718a4ea | 10.26434/chemrxiv.8311700.v2 | A Unified Electro- and Photocatalytic CO2 to CO Reduction Mechanism with Aminopyridine Cobalt Complexes | Mechanistic understanding of electro- and
photocatalytic CO<sub>2</sub> reduction is crucial to develop strategies to overcome
catalytic bottlenecks. In this regard, herein
it is presented a new CO<sub>2</sub>-to-CO reduction cobalt aminopyridine catalyst,
a detailed experimental and theoretical mechanistic study toward the
identification of bottlenecks and potential strategies to alleviate them. The combination
of electrochemical and <i>in-situ</i>
spectroelectrochemical (FTIR/UV-Vis SEC) studies together with spectroscopic
techniques (NMR, EXAFS) lead us to identify elusive key electrocatalytic
intermediates derived from complex [Co(py<sup>Me</sup>tacn)(OTf)<sub>2</sub>] (<b>1</b>)
(py<sup>Me</sup>tacn = 1-[2-pyridylmethyl]-4,7-dimethyl-1,4,7-triazacyclononane)
such as a highly reactive cobalt (I) (<b>1<sup>(I)</sup></b>) and cobalt (I)
carbonyl (<b>1<sup>(I)</sup>-CO</b>) species. <b>1<sup>(I)</sup></b> was
obtained by electrochemical reduction of <b>1<sup>(II)</sup></b>, and
characterized by NMR, EXAFS and FTIR/UV-Vis SEC. The combination of spectroelectrochemical
studies under CO<sub>2</sub>, <sup>13</sup>CO<sub>2</sub> and CO with DFT disclosed
that <b>1<sup>(I)</sup></b> directly reacts with CO<sub>2</sub> to form the
pivotal <b>1<sup>(I)</sup>-CO</b> intermediate at the <b>1<sup>(II/I) </sup></b>redox
potential. At this redox potential the theoretical energy barrier for the C-O
bond cleavage was found to be as low as 12.2 kcal·mol<sup>-1</sup>. However, the
catalytic process does not proceed at the <b>1<sup>(II/I) </sup></b>redox
potential, due to the formation of <b>1<sup>(I)</sup>-CO, </b>which is a thermodynamic
sink and the CO release restricts the electrocatalysis. In agreement with the
experimental observed CO<sub>2</sub>-to-CO electrocatalysis at the <b>1<sup>(I/0)
</sup></b>redox potential, computational studies suggested that the productive
electrocatalytic cycle involves striking metal carbonyl intermediates such as [L<sup>N4</sup>Co<sup>0</sup>CO]
(L<sup>N4</sup> = py<sup>Me</sup>tacn), [L<sup>N4</sup>Co<sup>II</sup>(CO<sub>2</sub>)CO]
and [L<sup>N4</sup>Co<sup>I</sup>CO)<sub>2</sub>]. In contrast, under photochemical
conditions, the catalytic process smoothly proceeds at the <b>1<sup>(II/I) </sup></b>redox
potential. Under the latter conditions,
it is proposed that the electron transfer rate is under diffusion control and then
the CO release from <b>1<sup>(II)</sup>-CO</b> is kinetically favored,
facilitating the catalysis. Finally, we have found that visible light
irradiation has a positive impact under electrocatalytic conditions.
We envision that light irradiation can serve
as an effective strategy to improve the CO<sub>2</sub> reduction of molecular
catalysts, <i>via</i> alleviating bottlenecks, such as the CO poisoning. | Sergio Fernández; Federico Franco; Carla Casadevall; Vlad Martin-Diaconescu; Josep M. Luis; Julio Lloret-Fillol | Coordination Chemistry (Inorg.); Small Molecule Activation (Inorg.); Spectroscopy (Inorg.); Computational Chemistry and Modeling; Electrocatalysis; Homogeneous Catalysis; Photocatalysis; Electrochemistry - Mechanisms, Theory & Study | CC BY NC ND 4.0 | CHEMRXIV | 2019-06-24 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/60c742d9702a9b08b718a4ea/original/a-unified-electro-and-photocatalytic-co2-to-co-reduction-mechanism-with-aminopyridine-cobalt-complexes.pdf |
60c7466f9abda26a3af8c739 | 10.26434/chemrxiv.11320460.v1 | Charge Reduction of Membrane Proteins in Native Mass Spectrometry Using Alkali Metal Acetate Salts | <p>Native mass spectrometry paired with ion mobility (IM-MS) provides the capacity to monitor the structure of protein complexes and simultaneously assess small molecule binding to the protein. Native IM-MS typically utilizes positive mode electrospray ionization producing a distribution of multiply charged protein species. For membrane proteins, these charge states are often too high resulting in protein gas phase unfolding or loss of noncovalent interactions. In an effort to reduce the charge of membrane proteins, the utility of alkali metal salts as a charge reducing additive was explored. Low concentrations of alkali metal salts caused marked charge reduction in the membrane protein, ELIC. The charge reducing effect was only present in membrane proteins, and could not be accounted for by conformational changes in ELIC structure. Charge reduction by alkali metal salts was also detergent dependent, and was most pronounced in long PEG-based detergents such as C10E5 and C12E8. Based on these results, a mechanism was posited for alkali metal charge reduction of membrane proteins. Addition of low concentration of alkali metals may provide an advantageous approach for charge reduction of detergent solubilized membrane proteins by native MS. <br /></p> | John T. Petroff II; Ailing Tong; Lawrence Chen; GregoryT. DeKoster; Farha Khan; Jeff Abramson; Carl Frieden; Wayland Cheng | Mass Spectrometry | CC BY NC ND 4.0 | CHEMRXIV | 2019-12-13 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/60c7466f9abda26a3af8c739/original/charge-reduction-of-membrane-proteins-in-native-mass-spectrometry-using-alkali-metal-acetate-salts.pdf |
6739eb3cf9980725cf7af4fc | 10.26434/chemrxiv-2024-m46zg | Unusual Hydrogen-mediated Oxidation in Doped Ceria Systems: Operando Insights | Ceria and doped-ceria are well-known material in heterogeneous catalysis due to their ability to catalyse are large number of redox reactions. They are a promising choice for solid oxide-based CO2 electrolysis cathodes due to their mixed ionic-electronic conducting nature. Gd and Pr doping is known to significantly improve both electrochemical and thermochemical reactions involving CO2 reduction. H2 in the feed stream was found to play a critical and unusual role in these reactions. This study systematically investigates the hydrogen’s impact on CO2 reduction within CeOx, Ce{Pr}Ox, and Ce{Gd}Ox. Operando Raman spectroscopy, combined with online mass spectrometry and optical imaging, revealed that CO production is linked to the reduction of Ce⁴⁺ to Ce³⁺ sites under bias. While dopants typically enhanced oxygen defect formation, Ce{Pr}Oₓ eliminated oxygen defects and tends to oxidize in H₂. First-principles calculations showed that hydrogen incorporation could stabilize or destabilize oxygen vacancies in the catalyst. It promotes reduction in CeOₓ and Ce{Gd}Oₓ, but counterintuitively stabilizes oxygen sites in Ce{Pr}Oₓ, leading to its oxidation. This study reports the first ever system which oxidized upon exposure to H2. | Vipin Kamboj; Soham Raychowdhury; chinmoy ranjan | Physical Chemistry; Catalysis; Energy; Electrocatalysis; Electrochemistry - Mechanisms, Theory & Study | CC BY NC ND 4.0 | CHEMRXIV | 2024-11-25 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/6739eb3cf9980725cf7af4fc/original/unusual-hydrogen-mediated-oxidation-in-doped-ceria-systems-operando-insights.pdf |
60c74e8abb8c1a4ccf3db777 | 10.26434/chemrxiv.12770225.v1 | A Rational Design of a Multi-Epitope Vaccine Against SARS-CoV-2 Which Accounts for the Glycan Shield of the Spike Glycoprotein | <p>The ongoing global health crisis caused by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), the virus which leads to Coronavirus Disease 2019 (COVID-19) has impacted not only the health of people everywhere, but the economy in nations across the world. While vaccine candidates and therapeutics are currently undergoing clinical trials, there is yet to be a proven effective treatment or cure for COVID-19. In this study, we have presented a synergistic computational platform, including molecular dynamics simulations and immunoinformatics techniques, to rationally design a multi-epitope vaccine candidate for COVID-19. This platform combines epitopes across Linear B Lymphocytes (LBL), Cytotoxic T Lymphocytes (CTL) and Helper T Lymphocytes (HTL) derived from both mutant and wild-type spike glycoproteins from SARS-CoV-2 with diverse protein conformations. In addition, this vaccine construct also takes the considerable glycan shield of the spike glycoprotein into account, which protects it from immune response. We have identified a vaccine candidate (a 35.9 kDa protein), named COVCCF, which is composed of 5 LBL, 6 HTL, and 6 CTL epitopes from the spike glycoprotein of SARS-CoV-2. Using multi-dose immune simulations, COVCCF induces elevated levels of immunoglobulin activity (IgM, IgG1, IgG2), and induces strong responses from B lymphocytes, CD4 T-helper lymphocytes, and CD8 T-cytotoxic lymphocytes. COVCCF induces cytokines important to innate immunity, including IFN-γ, IL4, and IL10. Additionally, COVCCF has ideal pharmacokinetic properties and low immune-related toxicities. In summary, this study provides a powerful, computational vaccine design platform for rapid development of vaccine candidates (including COVCCF) for effective prevention of COVID-19.</p> | William R. Martin; Feixiong Cheng | Drug Discovery and Drug Delivery Systems | CC BY NC ND 4.0 | CHEMRXIV | 2020-08-07 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/60c74e8abb8c1a4ccf3db777/original/a-rational-design-of-a-multi-epitope-vaccine-against-sars-co-v-2-which-accounts-for-the-glycan-shield-of-the-spike-glycoprotein.pdf |
6112e73742d16521c53d7023 | 10.26434/chemrxiv-2021-zgpzd-v2 | Frank-van der Merwe Growth in Bilayer Graphene | Bilayer graphene has attracted significant interest due to its unique properties, including fascinating electrical behavior when one layer is slightly rotated relative to the other. However, the quality of large-area bilayer graphene is often limited by the layer-plus-island growth mode in which islands of thicker graphene present as unavoidable impurities. Here, we report the observation of the layer-by-layer, Frank-van der Merwe (FM) growth mode in bilayer graphene where multilayer impurities are suppressed. Instead of the conventional surface adhesive energy, it is found that interface adhesive energy is possible to be tuned with an oxidative pretreatment. The FM-grown bilayer graphene is of AB-stacking or with small-twisting-angle (θ = 0-5°), which is more mechanically robust compared to monolayer graphene, facilitating a free-standing wet transfer technology. | Haozhe Wang; Zhenpeng Yao; Gang Seob Jung; Qichen Song; Marek Hempel; Tomas Palacios; Gang Chen; Markus J. Buehler; Alan Aspuru-Guzik; Jing Kong | Materials Science; Nanoscience; Nanostructured Materials - Nanoscience; Materials Chemistry | CC BY NC ND 4.0 | CHEMRXIV | 2021-08-11 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/6112e73742d16521c53d7023/original/frank-van-der-merwe-growth-in-bilayer-graphene.pdf |
6761451a6dde43c9086acf18 | 10.26434/chemrxiv-2024-x78bd-v2 | LlaMa meets Cheburashka: impact of cultural background for LLM quiz reasoning | Quiz games is the type of intellectual competition which are well suited for testing LLMs reasoning and problem solving skills. Indeed, a good quiz puzzle requires not only factual knowledge, but also the ability to analyze clues given in question, generate hypothesis, and choose the best one using logical reasoning and subtle hints. Recently, modern LLMs have made significant progress in general reasoning tasks, making this kind of evaluation extremely interesting. In this paper, we address a major limitation in the current LLMs' assessment: the models are usually evaluated on English language, or on the multi-lingual benchmarks reflecting English-centric culture, obtained by the translation from the English originals. In the contrary, we test the ability of the modern LLM to deal with the questions of real human quiz games from non-English-speaking society. Namely, we apply LlaMa3-405B to solve the quiz tasks created by the "What?Where?When?" Russian-speaking intellectual gaming community. First, we show, that although the LLM demonstrates strong reasoning and linguistic proficiency in Russian language, the performance diminishes significantly because of the poor knowledge of culture-specific facts. Second, we show the importance of the reasoning strategy choice for answering medium-difficulty questions, for which the model "posses" the necessary knowledge, but the correct answer cannot be given immediately. Evaluating several single- and multi-agent approaches, we obtain 6\% improvement in the overall accuracy comparing to the baseline step-by-step reasoning. | Mikhail Lifar; Bogdan Protsenko; Daniil Kupriianenko; Nazar Chubkov; Kirill Kulaev; Alexander Guda; Alexander Soldatov; Irina Piontkovskaya | Theoretical and Computational Chemistry; Theory - Computational; Machine Learning; Artificial Intelligence | CC BY NC 4.0 | CHEMRXIV | 2024-12-18 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/6761451a6dde43c9086acf18/original/lla-ma-meets-cheburashka-impact-of-cultural-background-for-llm-quiz-reasoning.pdf |
67bdbd0b81d2151a02fe217d | 10.26434/chemrxiv-2025-pz9m7 | Heated-to-Frozen Electrochemical Interphases Formation Strategy Enables Stable 4.5 V Li-metal Batteries in Ether-based Electrolyte | Formation of stable electrochemical interphases, including solid electrolyte interphase (SEI) and cathode electrolyte interphase (CEI) is crucial for developing high performance alkali metal batteries. The stability of SEI/CEI mainly depends on their chemistry and structure. Current studies on SEI/CEI design mainly focus on regulating their chemistry by tuning electrolyte formulations. In this work, we showcase that both the chemistry and structure of SEI/CEI could be readily regulated via a temperature modulated formation strategy. Specifically, pre-charging under heated condition was used to regulate the types and kinetics of electrolyte decomposition reactions, followed by frozen at low-temperature storage to control the deposition behavior of decomposition products on the electrode interface. Studies show that high temperatures pre-charging can affect the coordination structure of Li+ and accelerate the decomposition reaction kinetics, leading to large amount of anion decomposition. The subsequent low-temperature storage rapidly reduces the solubility of decomposition products generated at high temperatures, promoting the deposition of insoluble products on both electrodes, resulting in a dense and stable SEI/CEI. The robust SEI/CEI enables stable cycling of a 4.5 V Li||NCM811 cell in a medium-concentration ether-based electrolyte, achieving a capacity retention of 88.7% after 200 cycles at 0.5C (areal capacity 1.5 mAh cm-2). Even under practical conditions with a high NCM811 areal loading of 4.5 mAh cm-2, the battery maintained over 80% capacity retention after 130 cycles at 0.5C. This study not only offers an economical and efficient approach to enhance the cycling stability of high-voltage lithium metal batteries but, more importantly, provides new insights into strategies for controlling the formation of SEI to improve overall battery performance. | Yuwei Qian; Qingyu Dong; Ruowei Yi; Wujun Zhang; Xuechun Wang; Haiyang Zhang; Hui Shao; Patrice Simon; Yanbin Shen; Liwei Chen | Materials Science; Energy; Energy Storage; Materials Chemistry | CC BY NC ND 4.0 | CHEMRXIV | 2025-02-26 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/67bdbd0b81d2151a02fe217d/original/heated-to-frozen-electrochemical-interphases-formation-strategy-enables-stable-4-5-v-li-metal-batteries-in-ether-based-electrolyte.pdf |
628cd5b7809e325a8e9b0681 | 10.26434/chemrxiv-2022-0fz0p | Organophotocatalytic N–O Bond Cleavage of Weinreb Amides: Mechanism-Guided Evolution of a PET to ConPET Plat-form | A mild, organophotocatalytic N–O bond cleavage of Weinreb amides is disclosed, thereby expanding the chemistry of this venerable motif beyond acylation. This redox neutral process begins to reconcile the ubiquity of N–O bonds in contemporary synthesis with the disproportionately harsh, stoichiometric conditions that are often required for bond cleavage. The strategy is compatible with the parent alkyl derivatives (N–OMe, N–OAlkyl) thereby complementing tailored O-substituent approaches that require N–OAr groups (Ar = electron deficient). A broad range of acyclic and cyclic derivatives are dis-closed (>40 examples, up to 95%) and the synthetic utility of the method is demonstrated in a range of applications. In the case of cyclic Weinreb amide derivatives, this platform enables ambiphilic amide-aldehydes, of varying chain length, to be generated in a single transformation. Inspired by Emil Fischer´s seminal 1908 synthesis of aminoacetaldehyde using sodium amalgam, this method provides a milder route to access this important class of materials. Mechanistically-guided reaction development demonstrates the involvement of a photoinduced SET mechanism (PET), and this has been further advanced to a consecutive photoinduced electron transfer (ConPET) manifold: this has significantly expanded the scope of compatible substrates. | Julia Soika; Calum McLaughlin; Tomáš Neveselý; Constantin Daniliuc; John Molloy; Ryan Gilmour | Organic Chemistry; Catalysis; Physical Organic Chemistry; Organocatalysis; Photocatalysis | CC BY 4.0 | CHEMRXIV | 2022-05-25 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/628cd5b7809e325a8e9b0681/original/organophotocatalytic-n-o-bond-cleavage-of-weinreb-amides-mechanism-guided-evolution-of-a-pet-to-con-pet-plat-form.pdf |
60c74985f96a00a11f28728c | 10.26434/chemrxiv.12071508.v1 | Evaluation of Flavonoids as 2019-nCoV Cell Entry Inhibitor Through Molecular Docking and Pharmacological Analysis | In this study we aimed at the receipt binding domain of S protein and ACE-2 receptor as a promising drug targets against SARS-CoV-2. Flavonoids with anti-viral properties were taken as ligand for molecular docking. Selected flavonoids showed extremely good pharmacokinetics properties with good absorption, solubility, metabolism, excretion,distribution, bioavailability and minimal toxicity. These identified lead flavonoids may act as potential compound for the development of effective drugs and may help in controlling the rapid spread of SARS-CoV-2 by potentially inhibiting the virus entry into the host cell. | Deep Bhowmik; Rajat Nandi; Diwakar Kumar | Bioinformatics and Computational Biology | CC BY NC ND 4.0 | CHEMRXIV | 2020-04-06 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/60c74985f96a00a11f28728c/original/evaluation-of-flavonoids-as-2019-n-co-v-cell-entry-inhibitor-through-molecular-docking-and-pharmacological-analysis.pdf |
63f826b1937392db3df89437 | 10.26434/chemrxiv-2023-r12zw-v2 | Unraveling the Dynamic Correlations between Transition Metal Migrations and the Oxygen Dimer Formation in the Layered LiCoO2 Cathode | Expanding the voltage window is a common approach for increasing the practical capacity of the LiCoO2 cathode. However, it brings serious concerns such as structural degradations and the associated oxygen release induced by the transition metal (TM) cation migrations at a highly delithiated state. Therefore, it is crucial to understand the dynamic correlations between the TM cation migrations and the oxygen dimer formation. In this work, machine-learning-potential-assisted molecular dynamics simulations combined with enhanced sampling techniques are performed to resolve the above question using a representative CoO2 model. Our results show that the occurrence of the Co migrations exhibits local characteristics. The formation of two adjacent Co vacancies (the Co vacancy cluster) is necessary for the oxygen dimer generation. We further show that the introduction of the Ti dopant can significantly increase the kinetic barrier of the Co ion migration and thus effectively suppress the formation of the Co vacancy cluster. Overall, our work reveals the atomic-scale dynamic correlations between the TM migrations and the instability of the oxygen sublattice in the cathode material, and provides insights about the mechanism of the dopants promotion on the stability of cathode materials. | Taiping Hu; Fu-zhi Dai; Guobing Zhou; Xiaoxu Wang; Shenzhen Xu | Theoretical and Computational Chemistry; Physical Chemistry; Materials Science; Computational Chemistry and Modeling; Machine Learning; Electrochemistry - Mechanisms, Theory & Study | CC BY 4.0 | CHEMRXIV | 2023-02-24 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/63f826b1937392db3df89437/original/unraveling-the-dynamic-correlations-between-transition-metal-migrations-and-the-oxygen-dimer-formation-in-the-layered-li-co-o2-cathode.pdf |
60c73d94ee301c54e2c785ce | 10.26434/chemrxiv.13125401.v4 | On the State and Stability of Fuel Cell Catalyst Inks | <p></p><p>Catalyst layers (CL), as an active component of the catalyst coated membrane (CCM), form the heart of the proton electrolyte membrane fuel cell (PEMFC). For optimum performance of the fuel cell, obtaining suitable structural and functional characteristics for the CL is crucial. Direct tuning of the microstructure and morphology of the CL is non-trivial; hence catalyst inks as CL precursors need to be modulated, which are then applied onto a membrane to form the CCM. Obtaining favorable dispersion characteristics forms an important prerequisite in engineering catalyst inks for large scale manufacturing. In order to facilitate a knowledge-based approach for developing fuel cell inks, this work introduces new tools and methods to study both the dispersion state and stability characteristics, simultaneously. Catalyst inks were prepared using different processing methods, which include stirring and ultrasonication. The proposed tools are used to characterize and elucidate the effects of the processing method. Structural characterization of the dispersed particles and their assemblages was carried out by means of transmission electron microscopy. Analytical centrifugation (AC) was used to study the state and stability of the inks. Herein, we introduce new concepts, S score, and stability trajectory, for a time-resolved assessment of inks in their native state using AC. The findings were validated and rationalized using transmittograms as a direct visualization technique. The flowability of inks was investigated by rheological measurements. It was found that probe sonication only up to an optimum amplitude leads to a highly stable colloidal ink.<br /></p><br /><p></p> | Shalmali Bapat; Christopher Giehl; Sebastian Kohsakowski; Volker Peinecke; Michael Schäffler; Doris Segets | Carbon-based Materials; Electrochemistry; Quality Control; Fuel Cells; Interfaces; Structure | CC BY NC ND 4.0 | CHEMRXIV | 2021-06-09 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/60c73d94ee301c54e2c785ce/original/on-the-state-and-stability-of-fuel-cell-catalyst-inks.pdf |
60c74b08bdbb89e7d2a3949f | 10.26434/chemrxiv.11763555.v3 | Exposure to Mycotoxin-Mixtures via Breast Milk: An Ultra-Sensitive LC-MS/MS Biomonitoring Approach | Exposure to natural food contaminants during infancy may influence health consequences later in life. Hence, breast milk may serve as a vehicle to transport these contaminants, including mycotoxins, from mothers to their infants. Analytical methods mostly focused on single exposures in the past, thus neglecting co-occurrences and mixture effects. Here, we present a highly sensitive multi-biomarker approach by a sophisticated combination of steps during sample preparation including QuEChERS extraction followed by SPE cleanup and utilizing stable isotopes for compensating challenging matrix effects. The assay was validated in-house, reaching limits of detection (LOD) for all 34 analytes in the range of 0.1 to 300 ng/L with satisfying extraction efficiencies (75 - 109%) and stable intermediate precisions (1 - 18%) for most analytes. Compared a similar multi-mycotoxin assay for breast milk, LOD values were decreased by a factor of 2-60x enabling the assessment of chronic low-dose exposures. The new method was applied to a small set of Nigerian breast milk samples (n=3) to compare results with already published data. Concentration levels of samples that were found to be contaminated before could be confirmed. In addition, other mycotoxins were determined in all three samples, for example the newly investigated alternariol monomethyl ether (AME) was found for the first time in this biological fluid at concentrations up to 25 ng/L. Moreover, in a pooled Austrian sample obtained from a milk bank, trace amounts of multiple mycotoxins including AME (1.9 ng/L), beauvericin (5.4 ng/L), enniatin B (4.7 ng/L), enniatin B<sub>1</sub> ( | Dominik Braun; Chibundu N. Ezekiel; Doris Marko; Benedikt Warth | Analytical Chemistry - General; Environmental Analysis; Mass Spectrometry; Food | CC BY NC ND 4.0 | CHEMRXIV | 2020-04-30 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/60c74b08bdbb89e7d2a3949f/original/exposure-to-mycotoxin-mixtures-via-breast-milk-an-ultra-sensitive-lc-ms-ms-biomonitoring-approach.pdf |
66c5cd87a4e53c48761b524d | 10.26434/chemrxiv-2024-cl867 | Charge regulation of nanoparticles in the presence of multivalent electrolytes | We explore charge regulation (CR) of spherical nanoparticles immersed in an asymmetric electrolyte of a specified pH. Using a recently developed reactive canonical Monte Carlo (MC) simulation method, titration isotherms are obtained for suspensions containing monovalent, divalent, and trivalent coions. A theory based on the modified Poisson-Boltzmann (PB) approximation, which incorporates the electrostatic ion solvation free energy and discrete surface charge effects, is used to compare with the simulation results. A remarkably good agreement is found without any fitting parameters, both for the ion distributions and titration curves, suggesting that ionic correlations between coions and hydronium ions at the nanoparticle surface play only a minor role in determining the association equilibrium between hydroniums and the functional sites on the nanoparticle surface. On the other hand, if suspension contains multivalent counterions, we observe large deviation between theory and simulations, showing that the electrostatic correlations between counterions and hydronium ions at the nanoparticle surface are very significant and must be properly taken into account to correctly describe CR for such solutions | Thiago Escobar Colla; Amin Bakhshandeh; Yan Levin | Physical Chemistry; Biophysical Chemistry; Statistical Mechanics; Surface | CC BY 4.0 | CHEMRXIV | 2024-08-22 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/66c5cd87a4e53c48761b524d/original/charge-regulation-of-nanoparticles-in-the-presence-of-multivalent-electrolytes.pdf |
67a6dffb81d2151a0297a750 | 10.26434/chemrxiv-2025-cjj3v | Isotropically conducting tetraaryl osmium(IV), silane, and methane molecular wire junctions | Structural motifs based on tetraphenylmethane have drawn substantial interest as components of molecular electronic circuits, self-assembled monolayers, and three-dimensional polymers. However, the broad utility of such motifs is limited, for example, by the broken conjugation though the central, sp3-hybridized, carbon or silicon atom(s). To enrich their functionality, we reason the central atom could be exchanged for a transition metal to improve electronic coupling between the 𝜋-conjugated substituents and impart reversible redox properties. In evaluating this hypothesis, here we probe single-molecule junctions comprising oligoaryl wires with tetrahedral osmium(IV), silane, or methane centers. Surprisingly, we find that transport through junctions formed from the intact molecules in a non-polar, inert solvent appears largely independent of the central atom identity. In contrast, the conductance of junctions comprising an osmium(IV) wire can be modulated in an electrochemical environment by a factor of 47, to values 80× higher than for a silane analogue, by opening the bias window asymmetrically about the electrode Fermi level (EF). These measurements also indicate that such compounds can undergo in situ reactions that result in junctions comprising their dissociated oligoaryl arms, linked by chemisorbed Au-C(sp2) contacts. Our experimental results are supported by first principles calculations, which predict the osmium(IV) wires are substantially more conductive than the organic analogues due to their delocalized and well-coupled frontier orbitals with energies close to EF. This work highlights the promising potential of transition metal tetraaryl complexes as isotropic building blocks for functional circuits and extended materials, while opening avenues for further studies to enhance the connection between experimental observations and theoretical calculations. | Luana Zagami; Cynthia Avedian; Mukund Sharma; Andrew Fraire; Clarissa Olivar; Daniel Hernangómez-Pérez; Michael Inkpen | Physical Chemistry; Inorganic Chemistry; Nanoscience; Nanodevices; Organometallic Compounds; Transport phenomena (Physical Chem.) | CC BY NC ND 4.0 | CHEMRXIV | 2025-02-10 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/67a6dffb81d2151a0297a750/original/isotropically-conducting-tetraaryl-osmium-iv-silane-and-methane-molecular-wire-junctions.pdf |
679377c4fa469535b9a4d8d3 | 10.26434/chemrxiv-2025-rbqh1 | Electrical control of photon spin angular momentum in organic electroluminescent materials | The photon spin information encoded in circularly polarised (CP) light is of high interest for current and future technologies, including low power displays, encrypted communications and high performance quantum applications. Engineering organic light-emitting diodes (LED) to emit opposite handed electroluminescent CP light typically requires access to left- and right-handed chiral molecules. In conjugated polymer LEDs, the handedness of CP electroluminescence (EL) also depends on the active layer thickness or direction of current flow. For a given active layer thickness, it has remained unknown whether a single-handed chiral material can emit opposite handedness CP light in the same LED architecture – until now. Here we demonstrate organic LEDs where the handedness of the emitted CP EL can be controlled electrically, solely through the use of interlayers with no change in the emissive material composition or thickness. We reveal that this occurs due to a change in mechanism for the generation of CP EL, as a function of the recombination zone position within the device. This result provides a paradigm shift in the realisation of organic CP-LEDs with controllable spin angular momentum information and further contributes to ongoing discussions relating the fundamental physics of chiral optoelectronics. | Francesco Furlan; Michal Šámal; Jiří Rybáček; Andrea Taddeucci; Marta di Girolamo; Davide Nodari; Giuliano Siligardi; Jessica Wade; Binghai Yan; Irena Stará; Nicola Gasparini; Matthew Fuchter | Physical Chemistry; Materials Science; Polymer Science; Optical Materials; Thin Films; Organic Polymers | CC BY NC ND 4.0 | CHEMRXIV | 2025-01-27 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/679377c4fa469535b9a4d8d3/original/electrical-control-of-photon-spin-angular-momentum-in-organic-electroluminescent-materials.pdf |
60ccaea5926ad04a6301eb05 | 10.26434/chemrxiv-2021-2f4mc | Modular Enantioselective Synthesis of cis-Cyclopropanes through Redox-Active Carbene Transfer and Stereoselective Photo-Decarboxylation | Chiral cis-cyclopropanes are strained rigid analogs of alkyl chains, whose study and application is still limited by their difficult synthesis. A modular approach for the synthesis of this challenging structures from abundant olefins is enabled by the discovery of the electron donor-acceptor (EDA) interaction between 2-substituted benzothiazolines and N-hydroxyphtalimide esters. These complexes are activated by visible light without photocatalysts. In this system, the benzothiazoline reagent plays a triple role as photoreductant, stereoselective hydrogen atom donor and Brønsted acid. Beyond the enantioselective synthesis of cis-cyclopropanes, these results introduce benzothiazolines as accessible and easily tunable self-sensitized photoreductants. | Matteo Costantini; Abraham Mendoza | Biological and Medicinal Chemistry; Organic Chemistry; Catalysis; Organic Synthesis and Reactions; Photochemistry (Org.); Homogeneous Catalysis | CC BY NC ND 4.0 | CHEMRXIV | 2021-06-22 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/60ccaea5926ad04a6301eb05/original/modular-enantioselective-synthesis-of-cis-cyclopropanes-through-redox-active-carbene-transfer-and-stereoselective-photo-decarboxylation.pdf |
656f09925bc9fcb5c915ab44 | 10.26434/chemrxiv-2023-80b5h | Phytosulfokine Peptide Library: Chemical Synthesis and Biological Evaluation on Protoplast Regeneration | Phytosulfokine (PSK) is a highly conserved plant peptide hormone (PPH) containing two sulfated tyrosine residues. PSK acts as a growth factor in Arabidopsis thaliana plant species and significantly improves the efficiency of cellular proliferation in plant cell culture, a process known as regenaration. However, many important plant species are recalcitrant under exposure to PSK and require e.g., artificially generated PPHs to boost regeneration. Here, we report the design, chemical synthesis, and biological evaluation of the regeneration capacity of a PSK-like peptide library. Our set of thirteen PSK analogues included N-terminal modifications, amino acid substitutions, incorporation of diastereomers, and backbone N-methylation. Insertion of the latter required solution-phase synthesis of the proper building block prior to solid-phase peptide synthesis. The biological activity of the PSK analogues was assessed in the regeneration capacity of
Brassica oleracea cells (protoplasts). Most PSK analogues did not affect the regeneration capacity as compared to PSK. For example, when an alanine substitution was introduced and replaced either 2-Ile or 4-Thr, the bio-activity was fully abolished. However, 2-allo-Ile PSK and 4-Nme-Thr PSK showed increased activity in protoplast regeneration when compared with that of the native peptide. These findings indicated that introducing small chemical
modifications in the PPH PSK provides opportunities for inducing protoplast regeneration in recalcitrant species. | Jasper van de Sande; Dieuwertje Streefkerk; Richard Immink; Martijn Fiers; Bauke Albada | Organic Chemistry; Agriculture and Food Chemistry; Bioorganic Chemistry; Organic Synthesis and Reactions | CC BY NC ND 4.0 | CHEMRXIV | 2023-12-07 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/656f09925bc9fcb5c915ab44/original/phytosulfokine-peptide-library-chemical-synthesis-and-biological-evaluation-on-protoplast-regeneration.pdf |
65cf28f266c1381729c70206 | 10.26434/chemrxiv-2024-p484n | FragGT: Fragment-based evolutionary molecule generation with gene types | De novo molecular design is effective for optimizing compounds with desirable properties in drug discovery. In the realm of chemoinformatics, population-based evolutionary approaches have been known for over a decade including those that use retrosynthetically inspired fragment-based workflows to to balance the generation of synthesizable molecules with a sufficiently expressive molecular generator. We describe FragGT, a fragment-based de novo molecular design approach that uses an evolutionary algorithm to optimize molecules towards an objective function. We rely on the concept of gene types to hop between related molecular fragments where a fragment's gene type is defined by the nature of its connections to adjacent groups. We show that this simple approach achieves competitive performance on the GuacaMol benchmark suite with a low computational cost and the additional benefits of transparency and practicality. | Joshua Meyers; Nathan Brown | Theoretical and Computational Chemistry; Biological and Medicinal Chemistry; Drug Discovery and Drug Delivery Systems; Computational Chemistry and Modeling; Chemoinformatics - Computational Chemistry | CC BY 4.0 | CHEMRXIV | 2024-02-19 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/65cf28f266c1381729c70206/original/frag-gt-fragment-based-evolutionary-molecule-generation-with-gene-types.pdf |
678683ac81d2151a021293fb | 10.26434/chemrxiv-2025-mq7r4 | Geometric Orthogonality as a Recipe for Efficient Single-Molecule Charge Generation in Core Substituted NDI Derivatives | One of the primary drawbacks of organic materials, compared to their inorganic counterparts in various optoelectronic applications, is their lower charge generation efficiency, which stems from their inherently higher exciton binding energy. Therefore, new out-of-the-box approaches need to be introduced to the field. Herein, we propose a new approach to increase the charge formation of naphthalenediimide (NDI) derivatives by inducing a large torsional angle between the NDI core and the core-attached substituent, deconjugating the resulting extended π-system. To study the extent of this change, transient absorption spectroscopy characterisation has been performed on a set of derivatised NDI molecules where the core-attached substituents have been systematically altered to modulate the resulting torsional angle. The data clearly shows an enhanced charge generation with core-attached substituents from phenyl to anthracenyl which increase in both size and degree of rotational inhibition. This opens the possibility for a new family of NDI materials with implications for a wide range of applications such as photovoltaics, transistors and catalysis. | Hugh Britton; Alberto Santa Daría; Chao Lyu; Dejan-Krešimir Bučar; Alethea Tabor; Bob Schroeder; Sandra Gómez; Jose Manuel Marin-Beloqui | Physical Chemistry; Organic Chemistry; Organic Synthesis and Reactions; Physical and Chemical Properties; Spectroscopy (Physical Chem.); Materials Chemistry | CC BY NC ND 4.0 | CHEMRXIV | 2025-01-16 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/678683ac81d2151a021293fb/original/geometric-orthogonality-as-a-recipe-for-efficient-single-molecule-charge-generation-in-core-substituted-ndi-derivatives.pdf |
65de1b6566c1381729b0d700 | 10.26434/chemrxiv-2024-r57wp | PROSAC as a selection tool for SO-PLS regression: a strategy for multi-block data fusion | Spectral data from multiple sources can be integrated into multi-block fusion chemometric models, such as sequentially orthogonalized partial-least squares (SO-PLS), to improve the prediction of sample quality features. Pre-processing techniques are often applied to mitigate extraneous variability, unrelated to the response variables. However, the selection of suitable pre-processing methods and identification of informative data blocks becomes increasingly complex and time-consuming when dealing with a large number of blocks. The problem addressed in this work is the efficient pre-processing, selection and ordering of data blocks for targeted applications in SO-PLS. We introduce the PROSAC-SO-PLS methodology, which employs pre-processing ensembles with response-oriented sequential alternation calibration (PROSAC). This approach identifies the best pre-processed data blocks and their sequential order for specific SO-PLS applications. The method uses a stepwise forward selection strategy, facilitated by the rapid Gram-Schmidt process, to prioritize blocks based on their effectiveness in minimizing prediction error, as indicated by the lowest prediction residuals. To validate the efficacy of our approach, we showcase the outcomes of three empirical near-infrared (NIR) datasets. Comparative analyses were performed against partial-least-squares (PLS) regressions on single-block pre-processed datasets and a methodology relying solely on PROSAC. The PROSAC-SO-PLS approach consistently outperformed these methods, yielding significantly lower prediction errors. This has been evidenced by a reduction in the root-mean-squared error of prediction (RMSEP) ranging from 5 to 25% across seven out of the eight response variables analyzed. The PROSAC-SO-PLS methodology offers a versatile and efficient technique for ensemble pre-processing in NIR data modeling. It enables the use of SO-PLS minimizing concerns about pre-processing sequence or block order and effectively manages a large number of data blocks. This innovation significantly streamlines the data pre-processing and model-building processes, enhancing the accuracy and efficiency of chemometric models. | Jose Antonio Diaz-Olivares; Ryad Bendoula; Wouter Saeys; Maxime Ryckewaert; Ines Adriaens; Xinyue Fu; Matti Pastell; Jean-Michel Roger; Ben Aernouts | Theoretical and Computational Chemistry; Analytical Chemistry; Agriculture and Food Chemistry; Spectroscopy (Anal. Chem.) | CC BY NC ND 4.0 | CHEMRXIV | 2024-02-28 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/65de1b6566c1381729b0d700/original/prosac-as-a-selection-tool-for-so-pls-regression-a-strategy-for-multi-block-data-fusion.pdf |
6257ba775b900971910d9baa | 10.26434/chemrxiv-2022-8078d | A Strategy for Engineering High Photolysis Efficiency of Photocleavable Protecting Groups Through Cation Stabilization | Photolabile protecting groups (PPGs) enable the precise activation of molecular function with light in many research areas, such as photopharmacology, where remote spatiotemporal control over the release of a molecule is needed. The design and application of PPGs in recent years has particularly focused on the development of molecules with high molar absorptivity at long irradiation wavelengths. However, a crucial and until now mostly neglected parameter, pivotal to the efficiency of uncaging, is the photolysis quantum yield (QY). Here, we describe a novel and general approach to greatly increase the photolysis QY of heterolytic PPGs through stabilization of an intermediate chromophore cation. When applied to coumarin PPGs, our strategy resulted in systems possessing an up to 35-fold increase in QY and a convenient fluorescent readout during their uncaging, all while requiring the same number of synthetic steps for their preparation as the usual coumarin systems. We demonstrate that the same QY-engineering strategy applies to different photolysis payloads and even different classes of PPGs. Furthermore, analysis of the DFT-calculated energy barriers in the first singlet excited state have revealed valuable insights into the important factors that determine photolysis efficiency. The strategy reported herein will enable the development of efficient PPGs tailored for many applications. | Albert M. Schulte; Georgios Alachouzos; Wiktor Szymanski; Ben L. Feringa | Theoretical and Computational Chemistry; Biological and Medicinal Chemistry; Organic Chemistry; Photochemistry (Org.); Drug Discovery and Drug Delivery Systems; Computational Chemistry and Modeling | CC BY NC ND 4.0 | CHEMRXIV | 2022-04-15 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/6257ba775b900971910d9baa/original/a-strategy-for-engineering-high-photolysis-efficiency-of-photocleavable-protecting-groups-through-cation-stabilization.pdf |
62333d065c8dae6fedecc33e | 10.26434/chemrxiv-2021-gv8xk-v3 | Comparison of approximate intermolecular potentials
for ab initio fragment calculations on medium sized
N-heterocycles | The ground state intermolecular potential of bimolecular complexes of N-heterocycles is analysed for the impact of different terms of the interaction energy as provided by various, conceptually different theories.
Novel combinations with several formulations of the electrostatic, Pauli repulsion, dispersion and other contributions are tested for a good performance at both short- and long-distance sides of the potential energy surface for various alignments of the pyrrole dimer as well as the cytosine-uracil complex.
The integration of a DFT/CC density embedding scheme and dispersion terms from the effective fragment potential (EFP) method is found to provide very good agreement with the reference CCSD(T) potential overall, but a QM/MM approach using CHELPG atomic point charges for the electrostatic interaction augmented by EFP dispersion and Pauli repulsion contributions comes also close.
Both of these schemes has the advantage of not relying on predefined force fields, rather the interaction parameters can be obtained for the system under study, therefore excellent candidates for ab initio modeling. | Bónis Barcza; Ádám B. Szirmai; Katalin J. Szántó; Attila Tajti; Péter G. Szalay | Theoretical and Computational Chemistry; Computational Chemistry and Modeling | CC BY NC ND 4.0 | CHEMRXIV | 2022-03-18 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/62333d065c8dae6fedecc33e/original/comparison-of-approximate-intermolecular-potentials-for-ab-initio-fragment-calculations-on-medium-sized-n-heterocycles.pdf |
60c7416a567dfed33aec3da7 | 10.26434/chemrxiv.8052182.v1 | Hydrogen Bonding Guests Direct the Packing of a Small Organic Cage Molecule | <div>
<p>A small organic
cage molecule (<b>1</b>) containing six
nitrile groups was crystallized in the presence of a number of guests with
hydrogen bond donor groups, and from different solvents. In total, eight
crystal structures of <b>1</b> were
obtained, six of which are guest-free and two of which are co-crystals. When
the guest was resorcinol or pyrogallol co-crystals did not form, but the
presence of the guests directed formation of new crystalline phases that were
not observed when the cage was crystallized alone. When the guest was
hydroquinone or diaminobenzene, it was possible to isolate co-crystals where
the guest hydrogen bonds to some of the nitrile groups of the cage. </p>
</div>
<br /> | Thomas Anglim Lagones; Stephanie Boer; Nicholas White | Supramolecular Chemistry (Org.); Solid State Chemistry | CC BY NC ND 4.0 | CHEMRXIV | 2019-04-30 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/60c7416a567dfed33aec3da7/original/hydrogen-bonding-guests-direct-the-packing-of-a-small-organic-cage-molecule.pdf |
67c11d3a6dde43c908cca1bb | 10.26434/chemrxiv-2025-x0csm | eChem: Accelerated method development in quantum chemistry with notebooks | We have recently presented the eChem project as an interactive platform for quantum and computational chemistry education [J. Chem. Educ. 100, 1664--1671]. However, education is only one side of the eChem project. Another aspect is that it highly accelerates method development by means of code prototyping in notebooks. Complex equations can be understood and algorithms examined before the actual software programming step is carried out. Here, we illustrate the benefits of notebooks for code prototyping using the example of vibrational spectroscopy -- a type of spectroscopy which involves complex equations with a large number of terms. | Manuel Hodecker; Patrick Norman; Iulia Emilia Brumboiu | Theoretical and Computational Chemistry; Chemical Education; Chemical Education - General; Computational Chemistry and Modeling; Theory - Computational | CC BY NC ND 4.0 | CHEMRXIV | 2025-03-11 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/67c11d3a6dde43c908cca1bb/original/e-chem-accelerated-method-development-in-quantum-chemistry-with-notebooks.pdf |
60c749b8337d6ca0a7e2777b | 10.26434/chemrxiv.12101439.v1 | Discovery of Acid-Stable Oxygen Evolution Catalysts : High-throughput Computational Screening of Equimolar Bimetallic Oxides | Discovering acid-stable, cost-effective and active catalysts for oxygen evolution reaction (OER) is critical since this reaction is bottlenecking many electrochemical energy conversion systems. Current systems use extremely expensive iridium oxide catalysts. Identifying Ir-free or catalysts with reduced Ir-composition has been suggested as goals, but no systematic strategy to discover such catalysts has been reported. In this work, we performed high-throughput computational screening to investigate bimetalic oxide catalysts with space groups derived from those of IrO$_x$, identified promising OER catalysts predicted to satisfy all the desired properties: Co-Ir, Fe-Ir and Mo-Ir bimetallic oxides. We find that for the given crystal structures explored, it is essential to include noble metals to maintain the acid-stability, although one-to-one mixing of noble and non-noble metal oxides could keep the materials survive under the acidic conditions. Based on the calculated results, we provide insights to efficiently perform future high-throughput screening to discover catalysts with desirable properties. | Seoin Back; Kevin Tran; Zachary Ulissi | Electrocatalysis; Electrochemistry - Mechanisms, Theory & Study | CC BY NC ND 4.0 | CHEMRXIV | 2020-04-10 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/60c749b8337d6ca0a7e2777b/original/discovery-of-acid-stable-oxygen-evolution-catalysts-high-throughput-computational-screening-of-equimolar-bimetallic-oxides.pdf |
65608db3cf8b3c3cd704658b | 10.26434/chemrxiv-2023-1z161 | A high-performing spinel LiMn2O4 cathode material with unique morphology and scaled manufacture | High power application of Li battery remains a challenge due to the lack of suitable cathode materials that are stable at high current rates. Lithium manganese oxide (LiMn2O4 or LMO) spinel cathode is very promising due to its high operating voltage as well as fast charging ability, however, the associated Mn dissolution is one of the main hindrances to its practical applicability. In this work, we report a commercially scalable method (from 100 g to a few hundred kilograms of material) to develop novel lithium manganese oxide (LMO) electrode material with a unique multilayered morphology. This novel material (named CXL LMO) was tested in a Li metal cell where a reversible specific capacity of 110 mAh/g was achieved with 99% retention after 100 cycles. It showed excellent rate performance up to 20C current rate which is equivalent to 20 mA/cm2 current density. A Li-ion cell (CXL LMO|Graphite) was also reported with a practical areal capacity of 1 mAh/cm2 and showed stable behavior for more than 500 cycles. Cross-section morphology revealed the multi-layered structure was retained at the core of the novel LMO material and the structural integrity was maintained during cycling without any morphological degradation at a high rate and obtained lesser Mn dissolution compared to commercial LMO. The scalable synthesis procedure, high current rate stability, high cathode areal loading, and superior capacity retention make CXL LMO a promising candidate for high-power Li batteries. | Urbi Pal; Binayak Roy; Meisam Hasanpoor; Hamid Ilbeygi; Tiago Mendes; Robert Kerr; Lakshmi Vazhapully; Chris Song; Dabin Wang; Matt Boot-Handford; Mark Sceats; Maria Forsyth; Danah Al-Masri; Patrick Howlett | Energy; Chemical Engineering and Industrial Chemistry; Industrial Manufacturing; Energy Storage; Materials Chemistry | CC BY NC ND 4.0 | CHEMRXIV | 2023-11-27 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/65608db3cf8b3c3cd704658b/original/a-high-performing-spinel-li-mn2o4-cathode-material-with-unique-morphology-and-scaled-manufacture.pdf |
60c7580b842e65c1cbdb47cf | 10.26434/chemrxiv.14447982.v2 | Removal of Water-Soluble Inorganic Arsenicals with Phosphorene Oxide Nanoadsorbents: A First-Principles Study | A complete picture of the phosphorene oxide (PhosO) sorption properties for the simultaneous removal of inorganic As(III) and As(V) pollutants from water has been developed using first-principles calculations. Calculated adsorption energies, competitive adsorption with co-existing species, energy decomposition analyses (ALMO-EDA), implicitly/explicitly solvated geometries, and adsorption free energies provide deep insights into the adsorption mechanism as well as the origin of the strong selectivity sorption ability. The PhosO nanoadsorbents establish inner-sphere surface complexes with arsenicals even under competition with water molecules. These proposed structures also show a strong affinity with the highly mobile As(III), where energy saving is achieved by avoiding the pre oxidation process to convert As(III) into As(V) as requested in related materials. Results show that electrostatic driving forces govern the adsorption of neutral arsenicals, while the interplay between electrostatic and polarization phenomena drives the uptake of anionic arsenicals. By computing the adsorption strength as a function of the oxidation degree, the optimum adsorption efficiency is reached with a 25% in the content of oxidizing groups. In this oxidation degree, the strong repulsive surface charge at high pH turns the PhosO nanoadsorbents convenient to recycle via simple treatment with alkaline eluents. Finally, the adsorption ability remains thermodynamically allowed in a wide range of ambient temperatures (enthalpically governed reaction). Conceptually understanding the sorption properties of phosphorene-oxide-based materials towards arsenic pollutants provides a useful framework for future water treatment technologies.<br /> | Diego Cortes-Arriagada; Kerry Wrighton-Araneda | Aggregates and Assemblies; Alloys; Hybrid Organic-Inorganic Materials; Nanostructured Materials - Materials; Thin Films | CC BY 4.0 | CHEMRXIV | 2021-04-22 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/60c7580b842e65c1cbdb47cf/original/removal-of-water-soluble-inorganic-arsenicals-with-phosphorene-oxide-nanoadsorbents-a-first-principles-study.pdf |
62e39b41a8e4dc0f8c21e66e | 10.26434/chemrxiv-2022-d2xxj-v2 | Ferrocene as an electrochemical reporting surrogate of abasic sites in DNA | Methods for the real-time monitoring of the substrate acceptance of modified nucleotides by DNA polymerases are in high demand. In a step towards this aim, we have incorporated ferrocene-based abasic nucleotides into DNA templates and evaluated their compatibility with enzymatic synthesis of unmodified and modified DNA. All canonical nucleotides can be incorporated opposite ferrocene sites with a strong preference for purines. DNA polymerases with lesion-bypass capacity such as Dpo4 permit to resume DNA synthesis beyond the site of incorporation. Modified purine nucleotides can readily be incorporated opposite ferrocene basic site analogs, while pyrimidine nucleotides decorated with simple side-chains are also readily tolerated. These findings open up directions for the design of electrochemical sensing devices for the monitoring of enzymatic synthesis of modified DNA. | Chiara Figazzolo; Yifeng Ma; James Tucker; Marcel Hollenstein | Biological and Medicinal Chemistry; Chemical Biology | CC BY NC ND 4.0 | CHEMRXIV | 2022-07-29 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/62e39b41a8e4dc0f8c21e66e/original/ferrocene-as-an-electrochemical-reporting-surrogate-of-abasic-sites-in-dna.pdf |
66587038418a5379b0a75b04 | 10.26434/chemrxiv-2024-t0zn6 | Co-translocational Unfolding of HP35 in MIL-101(Cr) MOF | The immobilization of enzymes in the cages of Metal-Organic Frameworks (MOF) is important in biotechnology. In this context, the mechanism of translocation of proteins through the cavities of the MOF and the roles played by confinement and MOF chemistry in giving rise to stable protein intermediates that are otherwise transiently populated in physiological environment are important questions to be addressed. Herein, these unexplored aspects are examined with Villin Headpiece (HP35) as a model protein confined within a mesopore of MIL-101(Cr) using molecular dynamics simulations. At equilibrium, the protein is located farther from the center of the cavity and closer to the MOF surface. Molecular interactions with the MOF leads to a partial unfolding of helix-1 at its N-terminus. Umbrella sampling simulations inform the range of conformations that HP35 undertakes during the translocation from one cavity to another and also provide the free energy differences at various stages of translocation. Relative to its equilibrium state within the cavity, the free energy barrier for the unfolded protein at the cage window is estimated to be 16 kcal/mol. This study of MOF-based protein conformation can also serve as a general approach to observing intermediates in folding-unfolding pathways. | Oishika Jash; Anand Srivastava; Sundaram Balasubramanian | Theoretical and Computational Chemistry; Physical Chemistry; Materials Science; Computational Chemistry and Modeling; Theory - Computational; Thermodynamics (Physical Chem.) | CC BY NC ND 4.0 | CHEMRXIV | 2024-05-31 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/66587038418a5379b0a75b04/original/co-translocational-unfolding-of-hp35-in-mil-101-cr-mof.pdf |
6112f16b4cb4791ce52c8018 | 10.26434/chemrxiv-2021-t98xh-v2 | Studies of Catalyst-Controlled Regioselective Acetalization and Its Application to Single-Pot Synthesis of Differentially Protected Saccharides. | This article describes the studies on regioselective acetal protection of monosaccharide-based diols using chiral phos-phoric acids (CPAs) and their immobilized polymeric variants, (R)-Ad-TRIP-PS and (S)-SPINOL-PS as the catalysts. These catalyst-controlled regioselective acetalizations were found to proceed with high regioselectivities (up to >25:1 rr) on various D-glucose, D-galactose, D-mannose and L-fucose derived 1,2-diols, and could be carried in a re-giodivergent fashion depending on the choice of the chiral catalyst. The polymeric catalysts were conveniently recy-cled and reused multiple times for gram scale functionalizations with catalytic loading as low as 0.1 mol%, and their performance was often found to be superior to the performance of their monomeric variants. These regioselective CPA-catalyzed acetalizations were successfully combined with common hydroxyl group functionalizations as single-pot telescoped procedures to produce 34 regioisomerically pure differentially protected mono- and disaccharide de-rivatives. To further demonstrate the utility of the polymeric catalysts, the same batch of (R)-Ad-TRIP-PS catalyst was recycled and reused to accomplish single-pot gram-scale syntheses of 6 differentially protected D-glucose derivatives. The subsequent exploration of the reaction mechanism using NMR studies of deuterated and nondeuterated sub-strates revealed that low-temperature acetalizations happen via syn-addition mechanism, and that the reaction regi-oselectivity exhibits strong dependence on the temperature. The computational studies indicate complex tempera-ture-dependent interplay of two reaction mechanisms, one involving an anomeric phosphate intermediate and an-other via concerted asynchronous formation of acetal that results in syn-addition products. The computational models also explain the steric factors responsible for the observed C2-selectivities and are consistent with experimentally observed selectivity trends. | Sibin Wang; Oleksii Zhelavskyi; Jeonghyo Lee; Alonso J. Arguelles; Yaroslav Khomutnyk; Enoch A. Mensah; Hao Guo; Rami Hourani; Paul M. Zimmerman; Pavel Nagorny | Organic Chemistry; Catalysis; Organic Synthesis and Reactions; Heterogeneous Catalysis; Homogeneous Catalysis | CC BY NC ND 4.0 | CHEMRXIV | 2021-08-11 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/6112f16b4cb4791ce52c8018/original/studies-of-catalyst-controlled-regioselective-acetalization-and-its-application-to-single-pot-synthesis-of-differentially-protected-saccharides.pdf |
62585c8a5b900972380e32e9 | 10.26434/chemrxiv-2022-gzk0r | Polarizable MD and QM/MM Investigation of Acrylamide-based Leads to Target the Main Protease of SARS-CoV-2 | The main protease (Mpro) of SARS-CoV-2 is an essential enzyme for the replication of the virus causing the COVID-19 pandemic. Because there is no known homologue in humans, it has been proposed as a primary target for antiviral drug development. Here, we explore the potential of five acrylamide warhead molecules as possible leads to target MPro by polarizable MD and QM/MM calculations. All calculations involving a classical potential were calculated with the AMOEBA polarizable force field, while electronic structure calculations were performed within the framework of density functional theory. Our MD simulations show that at least one of the analyzed compounds may show promise as a lead for further development as a non-covalent inhibitor. The QM/MM calculations suggest that the compound could be considered as a non-covalent inhibitor, since the formation of a covalent bond with Cys145 has an unfavorable kinetic barrier for that compound. | Jorge Nochebuena; G. Andrés Cisneros | Theoretical and Computational Chemistry; Computational Chemistry and Modeling | CC BY NC ND 4.0 | CHEMRXIV | 2022-04-18 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/62585c8a5b900972380e32e9/original/polarizable-md-and-qm-mm-investigation-of-acrylamide-based-leads-to-target-the-main-protease-of-sars-co-v-2.pdf |
60c73f5c4c89192a41ad1f77 | 10.26434/chemrxiv.7327904.v1 | Cisplatin-Triggered Bioorthogonal Decaging of Amide Bonds for Targeted-Drug Activation in vivo | <p>Creating ways to control drug activation at specific tissues while sparing healthy tissues remains a major challenge. The administration of exogenous triggers offers the possibility for precise and traceless drug activation. However, ensuring localization of the trigger as well as the prodrug at the diseased tissue is complex while essential for therapeutic efficacy and to avoid side-toxicity. Cisplatin remains a first line option to treat 20% of all cancer patients and while clearing after 30 min from blood it concentrates in tumor tissues. Here, we demonstrate the use of the platinum-mediated bond cleavage of protected tertiary amides, which can occur in a catalytic manner under bioorthogonal conditions. Protected analogues of cytotoxic drugs 5-fluorouracil (5-FU) and monomethyl auristatin E (MMAE) were successfully activated using non-toxic amounts of platinum salts in cells. An otherwise fully stable and non-internalizing ADC built using a bifunctional linker featuring a tertiary amide protected MMAE was also bioorthogonally decaged in the presence of platinum salts for extracellular drug release. Finally, cisplatin-mediated activation of a prodrug 5-FU was shown in a colorectal zebrafish xenograft model leading to a significant tumor reduction. Considering cisplatin’s continued use as a first-choice treatment for many solid cancers and especially in colorectal cancer, we anticipate that our platinum-mediated decaging strategy will enhance cancer therapy by allowing tumor specific prodrug activation.</p> | Benjamin Stenton; Bruno Oliveira; João Conde; Magda Negrão; Miguel Godinho Ferreira; Rita Fior; Gonçalo Bernardes | Cell and Molecular Biology; Chemical Biology; Drug Discovery and Drug Delivery Systems; Organocatalysis | CC BY NC ND 4.0 | CHEMRXIV | 2018-11-13 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/60c73f5c4c89192a41ad1f77/original/cisplatin-triggered-bioorthogonal-decaging-of-amide-bonds-for-targeted-drug-activation-in-vivo.pdf |
60c73d4e842e65687edb1752 | 10.26434/chemrxiv.5318188.v2 | 10-step Synthesis of 20-nor-Salvinorin A by Dynamic Strategic Bond Analysis | Salvinorin
A (SalA) is a plant metabolite that agonizes the human <i>kappa</i>-opioid
receptor (κ-OR) with high affinity and high selectivity over <i>mu- </i>and <i>delta-</i>opioid
receptors. Its therapeutic potential has stimulated extensive semi-synthetic
studies and total synthesis campaigns. However, structural modification of SalA
has been complicated by its instability, and efficient total synthesis has been
frustrated by its dense, complex architecture. Treatment of strategic bonds in
SalA as dynamic and dependent on structural perturbation enabled the
identification of an efficient retrosynthetic pathway. Here we show that
deletion of C20 simultaneously stabilizes the SalA skeleton, simplifies its
synthesis and retains its high affinity and selectivity for the κ-OR. The
resulting 10-step synthesis now opens the SalA scaffold to deep-seated property
modification. | Jeremy Roach; Yusuke Sasano; Cullen Schmid; Saheem Zaidi; Vsevolod Katritch; Raymond Stevens; Laura Bohn; Ryan Shenvi | Natural Products; Organic Synthesis and Reactions | CC BY NC ND 4.0 | CHEMRXIV | 2017-08-19 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/60c73d4e842e65687edb1752/original/10-step-synthesis-of-20-nor-salvinorin-a-by-dynamic-strategic-bond-analysis.pdf |
65be51509138d231615a1369 | 10.26434/chemrxiv-2024-j3ph6 | Boiling of catechol secondary organic aerosol when heated to mild temperatures (36-52 °C) due to acetone and carbon dioxide formation and high viscosity | Thermal desorption measurements, including thermal desorption mass spectrometry, are often used to determine the volatility and chemical composition of secondary organic aerosol (SOA). Accurately interpreting such measurements requires understanding the response of SOA to heat. Using optical microscopy, we monitored catechol + O₃ SOA during heating at mild temperatures (36-52 °C). Catechol + O₃ SOA is a type of SOA formed in wildfire plumes. Surprisingly, the SOA particles appeared to boil when heated to these temperatures. We identified acetone and CO₂ as dominant species emitted from the SOA during heating, implying decomposition of the SOA components. Using mass spectrometry techniques, we observed catechol dimers to be the major product in unheated SOA and observed the degradation of these dimers after heating. Viscosity calculations suggested the mixing time of acetone and CO₂ within the particles was 11 h and 1 h at temperatures of 36 and 52 °C, respectively. The observed boiling can be explained by the production and slow mixing of acetone and CO₂ within the SOA particles when subjected to mild temperatures. Our results underscore the importance of considering decomposition, high viscosities, and slow mixing times when interpreting thermal desorption measurements of SOA, even when heating to mild temperatures. | Kristian J. Kiland; Katherine S. Hopstock; Ayomide A. Akande; Kristen N. Johnson; Yixin Li; Fabian Mahrt; Sepehr Nikkho; Barbara J. Finlayson-Pitts; Nadine Borduas-Dedekind; Sergey A. Nizkorodov; Allan K. Bertram | Earth, Space, and Environmental Chemistry; Atmospheric Chemistry | CC BY 4.0 | CHEMRXIV | 2024-02-07 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/65be51509138d231615a1369/original/boiling-of-catechol-secondary-organic-aerosol-when-heated-to-mild-temperatures-36-52-c-due-to-acetone-and-carbon-dioxide-formation-and-high-viscosity.pdf |
664cc7f821291e5d1ddfd35b | 10.26434/chemrxiv-2023-9kllm-v3 | Room-Temperature Strong Coupling between CdSe Nanoplatelets and a
Metal–DBR Fabry–Pérot Cavity | The generation of exciton–polaritons through strong light–matter interactions represents an emerging platform for exploring quantum phenomena. A significant challenge in colloidal nanocrystal-based polaritonic systems is the ability to operate at room temperature with high fidelity. Here, we demonstrate the generation of room-temperature
exciton–polaritons through the coupling of CdSe nanoplatelets (NPLs) with a Fabry–Pérot optical cavity, leading to
a Rabi splitting of 74.6 meV. Quantum-classical calculations accurately predict the complex dynamics between the
many dark state excitons and the optically allowed polariton states, including the experimentally observed lower polariton photoluminescence emission, and the concentration of lower polariton photoluminescence intensities at higher
in-plane momenta as the cavity becomes more negatively detuned. The Rabi splitting measured at 5 K is similar to
that at 300 K, validating the feasibility of the temperature-independent operation of this polaritonic system. Overall,
these results show that CdSe NPLs are an excellent material to facilitate the development of room-temperature quantum
technologies. | Ovishek Morshed; Mitesh Amin; Nicole M. B. Cogan; Eric R. Koessler; Robert Collison; Trevor M. Tumiel; William Girten; Farwa Awan; Lele Mathis; Pengfei Huo; A. Nickolas Vamivakas; Teri W. Odom; Todd D. Krauss | Physical Chemistry; Nanoscience; Optics; Quasiparticles and Excitations; Spectroscopy (Physical Chem.); Materials Chemistry | CC BY NC ND 4.0 | CHEMRXIV | 2024-05-22 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/664cc7f821291e5d1ddfd35b/original/room-temperature-strong-coupling-between-cd-se-nanoplatelets-and-a-metal-dbr-fabry-perot-cavity.pdf |
670896d4cec5d6c142d493e7 | 10.26434/chemrxiv-2024-dfp68 | Organometallic Nickel Complexes Supported by Pyridinophane Ligands and Their Oxidative Reactivity | The pyridinophane ligands RN3CX (X = H, Br) are well-established scaffolds that facilitat and stabilize nickel oxidative addition complexes to the proximal C(aryl)–X bond. In this study, we report the synthesis, detailed characterization, and reactivity of a series of Ni(II) and Ni(III) complexes supported by the MeN3CX ligand. Our findings demonstrate that Ni(II) complexes can be oxidized both chemically and aerobically to yield well-defined Ni(III) species. Excitingly, the Ni-disolvento complexes exhibit catalytic trifluoroethoxylation to generate the C–O coupled product. In addition, the Ni(III)-halide complex undergoes transmetallation with a Grignard reagent and subsequent C–C reductive elimination, while the β-hydride elimination side reaction is suppressed, outperforming its Ni(II) analogue. | Joshua Ji-Nung Leung; Dae Young Bae; Yusuff Moshood; Liviu M. Mirica | Inorganic Chemistry; Organometallic Compounds | CC BY NC ND 4.0 | CHEMRXIV | 2024-10-14 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/670896d4cec5d6c142d493e7/original/organometallic-nickel-complexes-supported-by-pyridinophane-ligands-and-their-oxidative-reactivity.pdf |
60c74b33bb8c1a34d03db170 | 10.26434/chemrxiv.12307214.v1 | Electroceutical Fabric Lowers Zeta Potential and Eradicates Coronavirus Infectivity upon Contact | Coronavirus with
intact infectivity attached to PPE surfaces pose significant threat to the
spread of COVID-19. We tested the hypothesis that an electroceutical fabric,
generating weak potential difference of 0.5V, disrupts the infectivity of
coronavirus upon contact by destabilizing the electrokinetic properties of the
virion. Respiratory coronavirus particles (10<sup>5</sup>) were placed in
direct contact with the fabric for 1 or 5 minutes. Viral particles (2.5-4x10<sup>4</sup>)
were recovered from the fabric. Following one minute of contact, zeta potential
of the coronavirus was significantly lowered indicating destabilization of its
electrokinetic properties. Size-distribution plot showed appearance of
aggregation of the virus. Testing of the cytopathic effects of the virus showed
eradication of infectivity as quantitatively assessed by PI-calcein and MTT
cell viability tests. This work provides the rationale to consider the studied
electroceutical fabric, or other materials with comparable property, as
material of choice for the development of PPE in the fight against COVID-19. | Abhishek Sen; Dolly Khona; Subhadip Ghatak; Vinoj Gopalakrishnan; Kenneth Cornetta; Sashwati Roy; Savita Khanna; Chandan Sen | Microbiology | CC BY NC ND 4.0 | CHEMRXIV | 2020-05-15 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/60c74b33bb8c1a34d03db170/original/electroceutical-fabric-lowers-zeta-potential-and-eradicates-coronavirus-infectivity-upon-contact.pdf |
67054c1151558a15ef82a574 | 10.26434/chemrxiv-2024-9ql22 | Photochemical Formation of Trifluoroacetic Acid: Mechanistic Insights into a Fluoxetine-Related Aryl-CF3 Compound | Trifluoroacetic acid (TFA) is a ubiquitous environmental contaminant; however, its sources are poorly constrained. One understudied source is from the photochemical reactions of aromatic compounds containing −CF3 moieties (aryl-CF3) including many pharmaceuticals and agrochemicals. Here, we studied the aqueous photochemistry of 4-(trifluoromethyl)phenol (4-TFMP), a known transformation product of the pharmaceutical fluoxetine. When exposed to lamps centred at UV-B, 4-TFMP formed up to 9.2% TFA at steady state under acidic conditions and 1.3% under alkaline conditions. TFA yields of fluoxetine were similar to 4-TFMP for acidic and neutral pH, but higher at alkaline pH, suggesting fluoxetine may have a mechanism of TFA formation in addition to via the 4-TFMP intermediate. Use of a 13CF3 isotopologue of 4-TFMP allowed for the tracking of TFA formation, which formed via multiple oxidative additions prior to oxidative ring cleavage. The oxidation is mediated by reactive oxygen species (ROS) generated through self-sensitized photolysis, with singlet oxygen and hydroxyl radicals as the key ROS. In addition to the TFA formation mechanism, other photochemical reactions of 4-TFMP resulted in defluorination and dimerization. Overall, this work expands the understanding of how TFA forms from aryl-CF3 compounds to better understand the total global burden of TFA. | Zhefei Guo; Azka Attar; Qiqige Qiqige; Rylan Lundgren; Shira Joudan | Earth, Space, and Environmental Chemistry; Environmental Science | CC BY NC ND 4.0 | CHEMRXIV | 2024-10-09 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/67054c1151558a15ef82a574/original/photochemical-formation-of-trifluoroacetic-acid-mechanistic-insights-into-a-fluoxetine-related-aryl-cf3-compound.pdf |
65d8833ce9ebbb4db9098cb5 | 10.26434/chemrxiv-2023-wgl32-v3 | Traversing Chemical Space with Active Deep Learning: A Computational Framework for Low-data Drug Discovery | Deep learning is accelerating drug discovery. However, current approaches are often affected by limitations in the available data, e.g., in terms of size or molecular diversity. Active deep learning has an untapped potential for low-data drug discovery, as it allows to improve a model iteratively during the screening process by acquiring new data, and to adjust its course along the way. However, several known unknowns exist when it comes to active learning: (a) what the best computational strategies are for chemical space exploration, (b) how active learning holds up to traditional, non-iterative, approaches, and (c) how it should be used in the low-data scenarios typical of drug discovery. These open questions currently limit the wider adoption of active learning in drug discovery. To provide answers, this study simulates a real-world low-data drug discovery scenario, and systematically analyses six active learning strategies combined with two deep learning architectures, on three large- scale molecular libraries. Not only do we show that active learning can achieve up to a six-fold improvement in hit discovery compared to traditional methods, but we also identify the most important determinants of its success in low-data regimes. This study lays the first-in-time foundations for the prospective use of active deep learning for low-data drug discovery and is expected to accelerate its adoption. | Derek van Tilborg; Francesca Grisoni | Biological and Medicinal Chemistry; Bioinformatics and Computational Biology; Chemical Biology; Drug Discovery and Drug Delivery Systems | CC BY 4.0 | CHEMRXIV | 2024-02-23 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/65d8833ce9ebbb4db9098cb5/original/traversing-chemical-space-with-active-deep-learning-a-computational-framework-for-low-data-drug-discovery.pdf |
63b515c781e4baf5e764749b | 10.26434/chemrxiv-2023-632qh | Beyond reduction cocatalysts: critical role of metal cocatalysts in photocatalytic oxidation of methane with water | Environmentally sustainable and selective conversion of methane to valuable chemicals under ambient conditions is pivotal for the development of next-generation photocatalytic technology. However, due to the lack of microscopic knowledge about non-thermal methane conversion, controlling and modulating photocatalytic oxidation processes driven by photogenerated holes remain a challenge. Here, we report novel function of metal cocatalysts to accept photogenerated holes and dominate the oxidation selectivity of methane, which is clearly beyond the conventional concept in photocatalysis that the metal cocatalysts loaded on the surfaces of semiconductor photocatalysts mostly capture photogenerated electrons and dominate reduction reactions exclusively. The novel photocatalytic role of metal cocatalysts was verified by operando molecular spectroscopy combined with real-time mass spectrometry for metal-loaded Ga2O3 model photocatalysts under methane gas and water vapor at ambient temperature and pressure. Our concept of metal cocatalysts that work as active sites for both photocatalytic oxidation and reduction provides a new understanding of photocatalysis and a solid basis for controlling the non-thermal redox reactions by metal-cocatalyst engineering. | Hikaru Saito; Hiromasa Sato; Taisuke Higashi; Toshiki Sugimoto | Physical Chemistry; Catalysis; Photocatalysis; Chemical Kinetics; Spectroscopy (Physical Chem.) | CC BY NC ND 4.0 | CHEMRXIV | 2023-01-04 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/63b515c781e4baf5e764749b/original/beyond-reduction-cocatalysts-critical-role-of-metal-cocatalysts-in-photocatalytic-oxidation-of-methane-with-water.pdf |
62f410d71803737bdea10353 | 10.26434/chemrxiv-2022-71n0n | Azide-Masked and Trehalose-based Fluorescence Turn-On Probe for Mycobacteria | A fluorescence turn-on probe, an azide-masked and trehalose-derivatized carbazole (Tre-Cz), was developed to image mycobacteria. The fluorescence turn-on is achieved by photoactivation of the aryl azide generating a fluorescent product through an efficient intramolecular C-H insertion reaction. The probe is highly specific for mycobacteria and could image mycobacteria in the presence of other Gram-positive and Gram-negative bacteria. Both the photoactivation and detection can be achieved using a handheld UV lamp, and bacteria of 103 CFU/mL or higher can be seen by the naked eye. The probe was also able to image mycobacteria spiked in sputum samples, although the detection sensitivity was lower. Studies using heat-killed, stationary phase and isoniazid-treated mycobacteria showed that metabolically active bacteria are required for the uptake of Tre-Cz. The uptake decreased in the presence of trehalose in a concentration dependent manner, indicating that Tre-Cz hijacks the trehalose uptake pathway. Mechanistic studies revealed that the trehalose recycling transporter LpqY-SugABC is the primary pathway for the uptake of Tre-Cz. The uptake was mostly diminished in the LpqY-SugABC deletion mutants ΔlpqY, ΔsugA and ΔsugB. For the mycolyl transferase antigen 85 complex (Ag85), however, only a slight reduction of uptake was observed in the Ag85 deletion mutant ΔAg85C, and no incorporation of Tre-Cz into the mycomembrane was observed. | Sajani Liyanage; N. G. Hasitha Raviranga; Julia Ryan; Scarlet Shell; Olof Ramstrom; Mingdi Yan | Biological and Medicinal Chemistry; Chemical Biology | CC BY NC ND 4.0 | CHEMRXIV | 2022-08-11 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/62f410d71803737bdea10353/original/azide-masked-and-trehalose-based-fluorescence-turn-on-probe-for-mycobacteria.pdf |
62e151eddc4c784f6141f403 | 10.26434/chemrxiv-2022-b1fh9-v3 | Reversed Conductance Decay of 1D Topological Insulators by Tight-Binding Analysis | Reversed conductance decay describes increasing conductance of a molecular chain series with increasing chain length. Realizing reversed conductance decay is an important step towards making long and highly conducting molecular wires. Recent work has shown that one-dimensional topological insulators (1D TIs) can exhibit reversed conductance decay due to their non-trivial edge states. The Su-Schrieffer-Heeger (SSH) model for 1D TIs relates to the electronic structure of these isolated molecules but not their electron transport properties as single-molecule junctions. Herein, we use a tight-binding approach to demonstrate that polyacetylene and other diradicaloid 1D TIs show a reversed conductance decay at the short chain limit. We explain these conductance trends by analyzing the impact of the edge states in these 1D systems on the single-molecule junction transmission. Additionally, we discuss how the self-energy from the electrode-molecule coupling and the on-site energy of the edge sites can be tuned to create longer wires with reversed conductance decays. | Liang Li; Suman Gunasekaran; Yujing Wei; Colin Nuckolls; Latha Venkataraman | Physical Chemistry; Electrochemistry - Mechanisms, Theory & Study | CC BY NC ND 4.0 | CHEMRXIV | 2022-07-28 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/62e151eddc4c784f6141f403/original/reversed-conductance-decay-of-1d-topological-insulators-by-tight-binding-analysis.pdf |
60c7479d702a9b458818ae14 | 10.26434/chemrxiv.11378643.v2 | Solvation and Speciation of Cobalt(II). A Theoretical X-Ray Absorption and RIXS Study | <p>The X-ray spectroscopic signatures of solvated Co<sup>2+</sup> ions mimicking the aqueous solution of CoCl<sub>2</sub> are investigated accounting for multiconfigurational as well as spin-orbit coupling effects. To this end the RASSCF/RASSI methodology with second order corrections due to dynamical correlation (RASPT2) is employed. Emphasis is put on the identification of spectral signatures of different species in octahedral, [Co(H<sub>2</sub>O)<sub>6</sub><sub>-</sub><sub>x</sub>Cl<sub>x</sub>]<sup>(2</sup><sup>-</sup><sup>x)+</sup>, and tetrahedral, [Co(H<sub>2</sub>O)<sub>4</sub><sub>-</sub><sub>x</sub>Cl<sub>x</sub>]<sup>(2</sup><sup>-</sup><sup>x)+</sup>,coordination. X-ray absorption spectra show distinct differences in the L<sub>3</sub> band only. Here, the best agreement is obtained for the hexa-aqua complex [Co(H<sub>2</sub>O)<sub>6</sub>]<sup>2+</sup>. For better identification it is proposed to use RIXS spectroscopy, which shows pronounced species-dependent inelastic features.</p><p><br /></p> | Basmah H. Allehyani; Walid I. Hassan; Saadullah Aziz; Rifaat H. Hilal; Oliver Kühn; Sergey I. Bokarev | Computational Chemistry and Modeling; Spectroscopy (Physical Chem.) | CC BY NC ND 4.0 | CHEMRXIV | 2020-01-21 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/60c7479d702a9b458818ae14/original/solvation-and-speciation-of-cobalt-ii-a-theoretical-x-ray-absorption-and-rixs-study.pdf |
60c750f2842e652676db3aea | 10.26434/chemrxiv.13102247.v1 | Oxidation Level and Glycidyl Ether Structure Determine Thermal Processability and Thermomechanical Properties of Arabinoxylan-Derived Thermoplastics | Herein we present arabinoxylan (AX)-based thermoplastics obtained by ring opening oxidation and subsequent reduction (dA-AX) combined with hydrophobization with three different glycidyl ethers [n-butyl (BuGE), isopropyl (iPrGE) and 2-ethylhexyl (EtHGE) glycidyl ether]. We also present the relationship of structural composition, thermal processing and thermomechanical properties. The BuGE and iPrGE etherified dA-AXs showed glass transition temperatures (T<sub>g</sub>) far below their degradation temperatures and gave thermoplastic materials when compression-molded at 140˚C. The BuGE (3 mole) etherified dA-AX films at 19 and 31 % oxidation levels exclusively exhibit 244 % (±42) and 267 % (±72) elongation. In contrast, iPrGE-dA-AX samples with shorter and branched terminals in the side chains had maximum 60 % (±19) elongation. The dramatic difference in elongation is assumed to be due to the presence of longer alkoxide chains, higher molar substitution and dual T<sub>g</sub> for the BuGE samples. Such superior elongation of AX thermoplastic films and its relationship with molar substitution and T<sub>g</sub> has not been reported before. | Parveen Kumar Deralia; Aline Maire du Poset; Anja Lund; Anette Larsson; Anna Ström; Gunnar Westman | Elastic Materials; Biopolymers; Cellulosic materials; Materials Chemistry | CC BY NC ND 4.0 | CHEMRXIV | 2020-10-16 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/60c750f2842e652676db3aea/original/oxidation-level-and-glycidyl-ether-structure-determine-thermal-processability-and-thermomechanical-properties-of-arabinoxylan-derived-thermoplastics.pdf |
65e6bc09e9ebbb4db9ed20fe | 10.26434/chemrxiv-2024-lnwnq | The Exotic Quasisolidity and Supersolidity of Water | Water is ubiquitously important but least known. This perspective features the latest finding of two exotic forms of water called quasisolid and supersolid phases due to the cooperativity and disparity of the O:H-O bond in its segmental length, energy, and specific heat when subjected to thermal, electric, and undercoordination perturbation. The quasisolid (QS) phase only appears at temperatures between melting and ice nucleation, regardless of sample size, and this phase has a negative thermal expansivity (NTE). However, polarization or molecular undercoordination creates the supersolid phase in skins of water and ice, droplets, ionic hydration cells, and volumetric water with a current flow or under a 106 eV/cm electric bias. This phase is characterized by ~10% H-O bond contraction and vibrating at ~3450 cm-1. The supersolid has unique properties such as high elasticity, mechanical strength, optical reflectivity, structure order, thermal stability, diffusivity, catalytic activity, and chemical reactivity. Liquid-QS-Ice transition with QS phase energy absorption occurs for water due to H-O bond contraction during thermal decay but not for the supersolid phase of saturated NaCl solution. The NTE of the QS fosters ice buoyancy and the supersolidity endows ice slipperiness, supercooling, superheating, premelting, low-temperature fiber elasticity, water bridge, and warm water fast cooling, as well as on water chemistry. | Changqing Sun | Physical Chemistry; Physical and Chemical Properties | CC BY 4.0 | CHEMRXIV | 2024-03-08 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/65e6bc09e9ebbb4db9ed20fe/original/the-exotic-quasisolidity-and-supersolidity-of-water.pdf |
623a7f37658bc025acb4be3b | 10.26434/chemrxiv-2022-3h55t | Cytochrome c as a distinct modulator of amyloid-beta amyloidogenesis in a peroxide-dependent manner
| Cytochrome c (Cyt c) is an important, multifunctional protein for controlling cell fate. Emerging evidence suggests a potential role of Cyt c in the amyloid pathology associated with Alzheimer’s disease (AD); however, the interaction between Cyt c and Abeta with the consequent impact on the aggregation and toxicity of Abeta is not known. Here we report the discovery that Cyt c can directly bind to Abeta and alter the aggregation and toxicity profiles of Abeta in a peroxide-dependent manner. Cyt c redirects Abeta peptides into less toxic, off-pathway amorphous aggregates in the presence of hydrogen peroxide (H2O2), whereas it accelerates Abeta fibrillization without H2O2. Such effects can be achieved by three possible mechanisms, including the complexation between Cyt c and Abeta, the oxidation of Abeta by Cyt c and H2O2, and the H2O2-mediated modification of Cyt c. Our studies demonstrate a new function of Cyt c as a modulator against Abeta amyloidogenesis. | Zhi Du; Eunju Nam; Yuxi Lin; Mannkyu Hong; Tamás Molnár; Ikufumi Kondo; Koichiro Ishimori; Mu-Hyun Baik; Young-Ho Lee; Mi Hee Lim | Biological and Medicinal Chemistry; Biochemistry; Chemical Biology | CC BY NC ND 4.0 | CHEMRXIV | 2022-03-23 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/623a7f37658bc025acb4be3b/original/cytochrome-c-as-a-distinct-modulator-of-amyloid-beta-amyloidogenesis-in-a-peroxide-dependent-manner.pdf |
60c74374337d6c44a3e26bee | 10.26434/chemrxiv.9206075.v1 | Modeling the Electrical Double Layer to Understand the Reaction Environment in a CO2 Electrocatalytic System | <p>The environment of a CO<sub>2</sub> electroreduction (CO<sub>2</sub>ER) catalyst is intimately coupled with the surface reaction energetics and is therefore a critical aspect of the overall system performance. The immediate reaction environment of the electrocatalyst constitutes the electrical double layer (EDL) which extends a few nanometers into the electrolyte and screens the surface charge density. In this study, we resolve the species concentrations and potential profiles in the EDL of a CO<sub>2</sub>ER system by self-consistently solving the migration, diffusion and reaction phenomena using the generalized modified Poisson-Nernst-Planck (GMPNP) equations which include the effect of volume exclusion due to the solvated size of solution species. We demonstrate that the concentration of solvated cations builds at the outer Helmholtz plane (OHP) with increasing applied potential until the steric limit is reached. The formation of the EDL is expected to have important consequences for the transport of the CO<sub>2</sub> molecule to the catalyst surface. The electric field in the EDL diminishes the pH in the first 5 nm from the OHP, with an accumulation of protons and a concomitant depletion of hydroxide ions. This is a considerable departure from the results obtained using reaction-diffusion models where migration is ignored. Finally, we use the GMPNP model to compare the nature of the EDL for different alkali metal cations to show the effect of solvated size and polarization of water on the resultant electric field. Our results establish the significance of the EDL and electrostatic forces in defining the local reaction environment of CO<sub>2</sub> electrocatalysts.</p> | Divya Bohra; Jehanzeb Chaudhry; Thomas Burdyny; Evgeny Pidko; wilson smith | Catalysts; Computational Chemistry and Modeling; Theory - Computational; Transport Phenomena (Chem. Eng.); Electrocatalysis; Energy Storage; Electrochemistry - Mechanisms, Theory & Study; Interfaces | CC BY 4.0 | CHEMRXIV | 2019-08-02 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/60c74374337d6c44a3e26bee/original/modeling-the-electrical-double-layer-to-understand-the-reaction-environment-in-a-co2-electrocatalytic-system.pdf |
6381ab186b4e8161a78005f7 | 10.26434/chemrxiv-2022-lbppx | pH Feedback Systems to Program Autonomous Self-Assembly and Material Lifecycles | pH-responsive systems have gained importance for the development of smart materials and for biomedical applications because they can switch between different states by simple acid/base triggers. However, such equilibrium systems lack the autonomous behavior that is so ubiquitous in living systems that self-regulate out of equilibrium. As a contribution to the emerging field of autonomous chemical systems, we have developed pH feedback systems (pH-FS) based on the coupling of acid- and base-producing steps in chemical reaction networks. The resulting autonomous nonlinear pH curves can be coupled with a variety of pH-sensitive building blocks to program the life cycles of the associated transient state at the level of self-assemblies and material systems. In this article, we discuss the different generations of such pH feedback systems, the principles of their coupling to self-assemblies with lifecycles and highlight emerging concepts for the design of autonomous functional materials. The specificity, robustness, and flexible operation of such pH-FS can also be used to realize chemical-structural and chemical-mechanical feedbacks that extend the behavior of such materials systems toward complex and functional life-like systems. | Charu Sharma; Indrajit Maity; Andreas Walther | Physical Chemistry; Self-Assembly | CC BY NC ND 4.0 | CHEMRXIV | 2022-11-28 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/6381ab186b4e8161a78005f7/original/p-h-feedback-systems-to-program-autonomous-self-assembly-and-material-lifecycles.pdf |
6650438721291e5d1d2510cd | 10.26434/chemrxiv-2024-llqpg | Comment on: The shape of water - how cluster formation explains the hydrophobic effect | A comment on the recently published article "The shape of water - how cluster formation explains the hydrophobic effect" regarding the possibility to simulate the hydrophobic effect with other available software tools. | Martin Andersson; Martin Richter | Physical Chemistry; Solution Chemistry; Thermodynamics (Physical Chem.) | CC BY 4.0 | CHEMRXIV | 2024-05-24 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/6650438721291e5d1d2510cd/original/comment-on-the-shape-of-water-how-cluster-formation-explains-the-hydrophobic-effect.pdf |
60c756880f50db29d03980e0 | 10.26434/chemrxiv.14264222.v1 | Rapid Removal of Fluoride from Water Using Core@shell and @Shell Nanoparticles of SiO2@ZrO2 and @ZrO2. Investigation of the Mechanisms Involved and Impact of Elemental Leaching | <p>Fluoride is a natural contaminant of
water that endangers many people worldwide when present in concentrations
higher than 2 ppm. Here, fluoride removal by four different nanostructured colloidal particles
(SiO<sub>2</sub>@ZrO<sub>2</sub><sup>nc</sup>, SiO<sub>2</sub>@ZrO<sub>2</sub><sup>c</sup>,
@ZrO<sub>2</sub><sup>nc</sup>, and @ZrO<sub>2</sub><sup>c</sup>) was measured
in batch systems within a period of 24 h. Surprisingly, these materials removed
fluoride from the water solutions and reached equilibrium in less than 10
minutes. The combination of high specific surface and fast fluoride removal
placed these materials among the top materials currently known in fluoride
removal. Also, the impact of element leaching was measured and quantified. The
influence of time, pH, and fluoride concentration on leaching of Zr and Si was
evaluated with a response surface methodology. Leaching of Zr and Si continued for several hours and depended on
first-order, quadratic and cross-product coefficients. Previous studies of
fluoride removal with zirconium oxide often assumed that a decrease in fluoride
concentration in the solution indicated that fluoride was bound to the surface
of the oxide. Zirconium oxide's solubility in water is low, but not zero.
Hence, Zr might have formed soluble fluorocomplexes. This is the first report
of fluoride removal with zirconium oxide that studied the leaching of the solid
to exclude the formation of soluble fluorocomplexes.</p> | Maisuls Iván; Yolanda Castro Martin; Alicia Duran; Dominic Lariviere; Pablo Arnal | Ceramics; Core-Shell Materials; Materials Chemistry | CC BY NC ND 4.0 | CHEMRXIV | 2021-03-23 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/60c756880f50db29d03980e0/original/rapid-removal-of-fluoride-from-water-using-core-shell-and-shell-nanoparticles-of-si-o2-zr-o2-and-zr-o2-investigation-of-the-mechanisms-involved-and-impact-of-elemental-leaching.pdf |
60c755fe567dfec882ec63b6 | 10.26434/chemrxiv.14176952.v1 | Identifying Fentanyl with Mass Spectral Libraries | <div>
<div>
<div>
<p>Synthesis, distribution and abuse of fentanyl, a synthetic opioid, has
led to a critical worldwide epidemic. Mass spectral library searching for
opioids remains unresolved despite being central to law-enforcement involving identification, monitoring and prosecution of opioid related crimes.
In this article, two model problems are presented to illustrate difficulties
associated with fentanyl identification. A collection of both currently-employed similarity measures and intuitive measures of dissimilarity are
employed to simulate identifying fentanyl analogs with mass spectral library searching.
</p>
</div>
</div>
</div> | Anthony J. Kearsley; Arun Moorthy | Mass Spectrometry | CC BY NC ND 4.0 | CHEMRXIV | 2021-03-11 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/60c755fe567dfec882ec63b6/original/identifying-fentanyl-with-mass-spectral-libraries.pdf |
614b59acaeaa6e7c58f61320 | 10.26434/chemrxiv-2021-4d07d | Improvement of the Gaussian Electrostatic Model by Separate Fitting of Coulomb and Exchange-Repulsion Densities and Implementation of a new Dispersion term | The description of each separable contribution of the intermolecular interaction is a useful approach to develop polarizable force fields (polFF). The Gaussian Electrostatic Model (GEM) is based on this approach, coupled with the use of density fitting techniques. In this work, we present the implementation and testing of two improvements of GEM: the Coulomb and Exchange-Repulsion energies are now computed with separate frozen molecular densities, and a new dispersion formulation inspired by the SIBFA polFF, which has been implemented to describe the dispersion and charge–transfer interactions. Thanks to the combination of GEM characteristics and these new features, we demonstrate a better agreement of the computed structural and condensed properties for water with experimental results, as well as binding energies in the gas phase with the ab initio reference compared with the previous GEM* potential. This work provides further improvements to GEM and the items that remain to be improved, and the importance of the accurate reproduction for each separate contribution. | Sehr Naseem-Khan; Jean-Philip Piquemal; G. Andrés Cisneros | Theoretical and Computational Chemistry | CC BY NC 4.0 | CHEMRXIV | 2021-09-23 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/614b59acaeaa6e7c58f61320/original/improvement-of-the-gaussian-electrostatic-model-by-separate-fitting-of-coulomb-and-exchange-repulsion-densities-and-implementation-of-a-new-dispersion-term.pdf |
60c74064bb8c1a2dde3d9dbc | 10.26434/chemrxiv.7731716.v1 | Aldehydes and Ketones Influence Reactivity and Selectivity in Nickel-Catalyzed Suzuki-Miyaura Reactions | We show that the energetically-favorable coordination of aldehydes and ketones – but not esters – to nickel(0) during Suzuki-Miyaura reactions can lead either to exquisite selectivity and enhanced reactivity, or to the inhibition<br />of the reaction. Aryl halides where the C-X bond is connected to the same π-system as an aldehyde or ketone functional<br />group undergo unexpectedly rapid oxidative addition, and are selectively cross-coupled during inter- and intramolecular<br />competition reactions. When aldehydes and ketones are present elsewhere, such as in the form of exogenous additives,<br />the cross-coupling reaction is inhibited depending on how strongly the pendant carbonyl group can coordinate to nickel(0). This work advances our understanding of how common functional groups interact with nickel(0) catalysts, and presents synthetic chemists with a tool that can be used to achieve site-selectivity in functionalized molecules.
<br /> | Alasdair Cooper; David Leonard; Sonia Bajo; Paul Burton; David Nelson | Organic Synthesis and Reactions; Physical Organic Chemistry; Computational Chemistry and Modeling; Homogeneous Catalysis; Kinetics and Mechanism - Organometallic Reactions; Transition Metal Complexes (Organomet.) | CC BY NC ND 4.0 | CHEMRXIV | 2019-02-19 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/60c74064bb8c1a2dde3d9dbc/original/aldehydes-and-ketones-influence-reactivity-and-selectivity-in-nickel-catalyzed-suzuki-miyaura-reactions.pdf |
6186ec6c3c169dcef8915c38 | 10.26434/chemrxiv-2021-ks58d | Stereoselective Palladium-Catalyzed C(sp3)–H Mono-Arylation of Piperidines and Tetrahydropyrans with a C(4) Directing Group | A selective Pd-catalyzed C(3)–H cis-functionalization of piperidine and tetrahydropyran carboxylic acids is achieved using a C(4) aminoquinoline amide auxiliary. High mono- and cis-selectivity is attained by using mesityl carboxylic acid as an additive. Conditions are developed with significantly lower reaction temperatures (≤50 °C) than other reported heterocycle C(sp3)–H functionalization reactions, which is facilitated by a DoE optimization. A one-pot C–H functionalization-epimerization procedure provides the trans-3,4-disubstituted isomers directly. Divergent aminoquinoline removal is accomplished with the installation of carboxylic acid, alcohol, amide and nitrile functional groups. Overall fragment compounds suitable for screening are generated in 3–4 steps from readily-available heterocyclic carboxylic acids. | Amalia-Sofia Piticari; Daniele Antermite; Joe I. Higham; J. Harry Moore; Matthew P. Webster; James A Bull | Organic Chemistry; Catalysis; Organic Synthesis and Reactions; Stereochemistry; Homogeneous Catalysis | CC BY 4.0 | CHEMRXIV | 2021-11-08 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/6186ec6c3c169dcef8915c38/original/stereoselective-palladium-catalyzed-c-sp3-h-mono-arylation-of-piperidines-and-tetrahydropyrans-with-a-c-4-directing-group.pdf |
64f7471679853bbd78275e41 | 10.26434/chemrxiv-2022-7ddw5-v3 | Predictive Minisci and P450 Late Stage Functionalization with Transfer Learning | Structural diversification of lead molecules is a key component of drug discovery to explore chemical space. Late stage functionalizations (LSFs) are versatile methodologies capable of installing functional handles on richly decorated intermediates to deliver numerous diverse products in a single reaction. Predicting the regioselectivity of LSF is still an open challenge in the field. Numerous efforts from chemoinformatics and machine learning (ML) groups have made significant strides in this area. However, it is arduous to isolate and characterize the multitude of LSF products generated, limiting available data and hindering pure ML approaches. We report the development of an approach that combines a message passing neural network and 13C NMR-based transfer learning to predict the atom-wise probabilities of functionalization for Minisci and P450-based functionalizations. We validated our model both retrospectively and with a series of prospective experiments, showing that it accurately predicts the outcomes of Minisci-type and P450 transformations and outperforms the well-established Fukui-based reactivity indices and other machine learning reactivity-based algorithms. | Emma King-Smith; Felix A. Faber; Usa Reilly; Anton V. Sinitskiy; Qingyi Yang; Bo Liu; Dennis Hyek; Alpha A. Lee | Theoretical and Computational Chemistry; Organic Chemistry; Organic Synthesis and Reactions; Machine Learning; Artificial Intelligence | CC BY NC ND 4.0 | CHEMRXIV | 2023-09-06 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/64f7471679853bbd78275e41/original/predictive-minisci-and-p450-late-stage-functionalization-with-transfer-learning.pdf |
6320e680be03b29bb1f4d298 | 10.26434/chemrxiv-2022-mrptw-v2 | Structure-based discovery of multitarget directed anti-inflammatory p-nitrophenyl hydrazones; molecular docking, drug-likeness, in-silico pharmacokinetics, and toxicity studies. | We designed novel p-nitrophenyl hydrazones as multi-target inhibitors of COX-2, 5-LOX, and H+/K+ ATPase in a bid to overcome side effects associated to NSAIDs and coxibs. Specifically, compounds 1-(4-nitrophenyl)-2-[(3,4,5-trimethoxyphenyl)methylidene] hydrazine (3), 4-hydroxy-2-methyl-6-[(2-(4-nitrophenyl)hydraz-1-ylidene)methyl]thiochroman-1,1-dioxide (6), 4-methoxy-2-methyl-6-[(2-(4-nitrophenyl)hydraz-1-ylidene)methyl]thiochroman-1,1-dioxide (8), 2-methyl-6-[(2-(4-nitrophenyl)hydraz-1-ylidene)methyl]-4-(trifluoromethyl)thiochroman-1,1-dioxide (11), 4-[(2-(4-nitrophenyl)hydraz-1-ylidene)methyl]benzenesulfonamide (13), 4-[(2-(4-nitrophenyl)hydraz-1-ylidene)methyl]-3-(trifluoromethyl)benzenesulfonamide (14), 5-methyl-6-{4-[(2-(4-nitrophenyl)hydraz-1-ylidene)methyl]phenyl}-2,3,4,5-tetrahydropyridazin-3-ol (16), and 5-methyl-6-{4-[(2-(4-nitrophenyl)hydraz-1-ylidene)methyl]phenyl}-4,5-dihydropyridazin-3(2H)-one (17) indicated promise as potent multi-target inhibitors of COX-2, 5-LOX, and H+/K+ ATPase with potential anti-inflammatory activity devoid of adverse effects of NSAIDs. Interactions with important amino acids which are key for ant-inflammatory activity and proton pump inhibition were noticed. All the compounds are less COX-2 selective compared to celecoxib. These compounds in addition have shown druglike physicochemical properties, passed Lipinski’s, Egan’s, Veber’s, Muegge’s and Ghose’s rules for druglike small molecules and orally bioavailable drugs. The compounds also passed golden triangle’s rule for potent and metabolically stable drugs. Also, these compounds passed Pfizer and GSK rules. The compounds also indicated excellent pharmacokinetic profiles complementing their potential anti-inflammatory activity with apparent safety profiles. | Sodeeq Babalola; Nosakhare Igie; Isaiah Odeyemi | Biological and Medicinal Chemistry; Drug Discovery and Drug Delivery Systems | CC BY NC ND 4.0 | CHEMRXIV | 2022-09-14 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/6320e680be03b29bb1f4d298/original/structure-based-discovery-of-multitarget-directed-anti-inflammatory-p-nitrophenyl-hydrazones-molecular-docking-drug-likeness-in-silico-pharmacokinetics-and-toxicity-studies.pdf |
60c73eda842e65e290db19ac | 10.26434/chemrxiv.7135928.v1 | Multi- and In-Stabilities in Gas Partitioning Between Nanoporous Materials and Rubber Balloons | <div>In the two-balloon experiment, two rubber balloons are connected and allowed to exchange gas. Owing to the non-monotonic relationship between the radius of the balloon and the pressure of gas inside of it, the two-balloon system presents multi- and in-stabilities.</div><div><br /></div><div>Herein, we consider a two-adsorbent system, where two different adsorbents are allowed to exchange gas. We show that, for rigid adsorbents, the thermodynamic equilibrium state is unique.</div><div><br /></div><div>Then, we consider an adsorbent-balloon system, where an adsorbent exchanges gas with a rubber balloon. This system can exhibit multiple states at thermodynamic equilibrium-- two (meta)stable and one unstable. The size of the balloon, pressure of gas in the balloon, and partitioning of gas between the adsorbent and the balloon differ among the equilibrium states. Temperature changes and the addition/removal of gas into/from the adsorbent-balloon system can induce catastrophe bifurcations and show hysteresis. Furthermore, the adsorbent-balloon system exhibits a critical temperature where, when approached from below, the discrepancy of balloon size between the two (meta)stable states decreases and, beyond, bistability is impossible.</div><div><br /></div><div>Practically, our findings preclude multiple partitions of adsorbed gas in rigid mixed-linker metal-organic frameworks and may inspire new soft actuator and sensor designs.</div> | Cory Simon; carlo carraro | Elastic Materials; Hybrid Organic-Inorganic Materials; Nanostructured Materials - Materials; Thermodynamics (Chem. Eng.); Statistical Mechanics; Thermodynamics (Physical Chem.) | CC BY NC ND 4.0 | CHEMRXIV | 2018-09-27 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/60c73eda842e65e290db19ac/original/multi-and-in-stabilities-in-gas-partitioning-between-nanoporous-materials-and-rubber-balloons.pdf |
6226c30c97f2101b42010f8c | 10.26434/chemrxiv-2022-2br4r | Trace Residue Identification, Characterization and Longitudinal Monitoring of the Novel Synthetic Opioid β-U10, from Discarded Drug Paraphernalia | Empirical data regarding dynamic alterations in illicit drug supply markets in response to the COVID-19 pandemic, including the potential for introduction of novel drug substances and/or increased poly-drug combinations at the ‘street’ level (i.e., directly proximal to the point of consumption), is currently lacking. Here, a high-throughput strategy employing ambient ionization-mass spectrometry is described for the trace residue identification, characterization and longitudinal monitoring of illicit drug substances found within >6,600 discarded drug paraphernalia (DDP) samples collected during a pilot study of an early warning system for illicit drug use in Melbourne, Australia from August 2020-February 2021, while significant COVID-19 lockdown conditions were imposed. The utility of this approach is demonstrated for the de novo identification and structural characterization of β-U10, a previously unreported naphthamide analogue within the ‘U-series’ of synthetic opioid drugs, including differentiation from its α-U10 isomer without need for sample preparation or chromatographic separation prior to analysis. Notably, β-U10 was observed with 23 other drug substances, most commonly in temporally distinct clusters with heroin, etizolam and diphenhydramine, and in a total of 182 different poly-drug combinations. Finally, longitudinal monitoring of the number and weekly ‘average signal intensity’ (ASI) values of identified substances, developed here as a semi-quantitative proxy indicator of changes in availability, relative purity and compositions of street level drug samples, revealed that increases in the number of identifications and ASI for β-U10 and etizolam coincided with a 50% decrease in the number of positive detections and an order of magnitude decrease in the ASI for heroin. | Henry West; John Fitzgerald; Katherine Hopkins; Michael Leeming; Matthew Di Rago; Dimitri Gerostamoulos; Nicolas Clark; Paul Dietze; Jonathan White; James Ziogas; Gavin Reid | Analytical Chemistry; Mass Spectrometry | CC BY NC ND 4.0 | CHEMRXIV | 2022-03-09 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/6226c30c97f2101b42010f8c/original/trace-residue-identification-characterization-and-longitudinal-monitoring-of-the-novel-synthetic-opioid-u10-from-discarded-drug-paraphernalia.pdf |
60c74ba8702a9b9aa318b4ce | 10.26434/chemrxiv.12362618.v1 | Establishment and Validation of a Drug-Target Microarray for SARS-CoV-2 | <p>COVID-19 has become one of the worst epidemic in the world, currently already more than four million people have been infected, which probably co-exist with human beings, and has a significant impact on the global economy and political order. In the process of fighting against the epidemic in China, the clinical value of a variety of herbal medicines has been recognized and written into the clinical application guide. However, their effective molecular mechanism and potential targets are still not clear. Pathology and pharmacology research will gradually attract attention in the post-epidemic outbreak term. Here, we constructed a COVID-19 protein microarray of potential therapy targets, which contains the main drug targets to the SARS-COV-2 virus and the anti-virus, anti-inflammatory cellar targets of the host. Series of quality controls test has been carried out, which showed that it could be applied for drug target screening of bio-active natural products. The establishment of this microarray will provide a useful tool for the study of the molecular pharmacology of natural products.</p> | Peng Chen; Zehua Zeng; Hongwu Du | Biochemical Analysis; High-throughput Screening | CC BY NC 4.0 | CHEMRXIV | 2020-05-27 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/60c74ba8702a9b9aa318b4ce/original/establishment-and-validation-of-a-drug-target-microarray-for-sars-co-v-2.pdf |
64af72b49ea64cc167eef141 | 10.26434/chemrxiv-2023-npjhq-v2 | Understanding and Control of Zener Pinning via Phase Field and Ensemble Learning | Zener pinning refers to the dispersion of fine particles which influences grain size distribution \textit{via} movement of grain boundaries in a polycrystalline material. Grain size distribution in polycrystals has a significant impact on their properties including physical, chemical, mechanical, and optical to name a few. We explore the use of Phase-field modeling and machine-learning techniques to understand and improve the control of grain size distribution \textit{via} Zener pinning in polycrystalline materials. We develop a machine learning model that determines the relative importance of various parameters to exercise microstructure control \textit{via} Zener pinning. Our workflow combines high-throughput phase-field simulations and machine learning to address the computational bottlenecks associated with large-scale simulations as well as identify features necessary for microstructure control in polycrystals. A random forest (RF) regression model was developed to predict grain sizes based on five Phase-field model parameters, achieving an average prediction error of 0.72 nm for the training data and 1.44 nm for the test data. The importance of the input parameters is analyzed using the SHapley Additive exPlanations (SHAP) approach which reveals that diffusivity, volume fraction, and particle diameter are the most important parameters in determining the final grain size. These findings will allow us to select the best second-phase particles, optimize grain size distributions and thus design microstructures with the desired properties. The developed method is a highly versatile and generalizable approach that can be used to assess the combined effects of individual features in the presence of multiple variables. | Sukriti Manna; Henry Chan; Avishek Ghosh; Tamoghna Chakraborti; Subramanian Sankaranarayanan | Materials Science; Nanoscience; Alloys; Ceramics | CC BY 4.0 | CHEMRXIV | 2023-07-17 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/64af72b49ea64cc167eef141/original/understanding-and-control-of-zener-pinning-via-phase-field-and-ensemble-learning.pdf |
655f16055bc9fcb5c9304377 | 10.26434/chemrxiv-2023-0p4pb | Hidden Boron Catalysis: A Simple Colourimetric Indicator | ‘Hidden’ catalysis plagues the development and understanding of all catalytic processes. Hidden acid catalysis and catalysis by trace metal contamination being two widely recognised examples. Since 2010, over 600 new catalysed hydroboration protocols have been reported despite the prevalence of hidden borane catalysis across hydroboration reactions using HBcat and HBpin. Nucleophilic species, present as either activators, additives or inherent to the catalyst structure, readily mediate the decomposition of HBpin and HBcat to boranes, including (ligated) BH3. These boranes are themselves catalysts for alkene and alkyne hydroboration, so often serve as the active, ‘hidden’, catalyst rather than the intended metal/metalloid species reported as a the ‘catalyst’. Following our introduction of the TMEDA test for hidden borane catalysis 2020, the proportion of catalysed hydroboration publications testing for hidden borane catalysis has increased from 5% to 23%, but this is still well short of routine. We now report, a simple, rapid and colourimetric method for the determination of hidden borane catalysis. This method uses nothing more than a colour change visible to the naked eye, akin to litmus paper acid/base indicators. The colourimetric test uses a bench-stable, widely commercially-available reagent, crystal violet, at low concentration to identify hidden borane catalysis in seconds. in situ BH3 formation from the decomposition of HBpin by species from across the periodic table has been positively identifed using this new test. The colourimetric indicator does inhibit the hydroboration reaction and shows no reactivity with substrates, HBpin, HBcat, nucleophilic species or any of the ‘catalysts’ tested. This test is easily applied to all past and future catalysed hydroboration reactions and represents the first example of a colour indicator for hidden catalysis. | Julie Macleod; Stephen Thomas | Organic Chemistry; Catalysis; Organic Synthesis and Reactions; Homogeneous Catalysis; Organocatalysis | CC BY 4.0 | CHEMRXIV | 2023-11-23 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/655f16055bc9fcb5c9304377/original/hidden-boron-catalysis-a-simple-colourimetric-indicator.pdf |
62dfb097e7fc8fb5b78903a8 | 10.26434/chemrxiv-2022-b601x | Deconvolution of Electrochemical Impedance Spectroscopy Data Using the Deep-Neural-Network-Enhanced Distribution of Relaxation Times | Electrochemical impedance spectroscopy (EIS) is a characterization technique widely used to evaluate the properties of electrochemical systems. The distribution of relaxation times (DRT) has emerged as a model-free alternative to equivalent circuits and physical models to circumvent the inherent challenges of EIS analysis. Deep neural networks (DNNs) can be used to deconvolve DRTs, but several issues remain, e.g., the long training time, the DNN accuracy, and the deconvolution of DRTs with negative peaks. The DNN-DRT model was developed here to address these fundamental limitations. Specifically, a pretraining step was included to decrease the computation time. A thorough error analysis was also conducted to evaluate the different components of the DRT and impedance errors to ultimately decrease them. Lastly, the training loss function was modified to handle DRTs with negative peaks. These different advances were validated with an array of synthetic EIS spectra and real EIS spectra from a lithium-ion battery, a solid oxide fuel cell, and a proton exchange membrane fuel cell. Moreover, this new model outperformed in most cases the previously developed DRTtools and deep-DRT model. Overall, we envision that this research will open the venue for more DNN-based analyses of EIS data for electrochemical systems. | Emanuele Quattrocchi; Baptiste Py; Adeleke Maradesa; Quentin Meyer; Chuan Zhao; Francesco Ciucci | Energy; Energy Storage; Fuel Cells | CC BY 4.0 | CHEMRXIV | 2022-07-26 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/62dfb097e7fc8fb5b78903a8/original/deconvolution-of-electrochemical-impedance-spectroscopy-data-using-the-deep-neural-network-enhanced-distribution-of-relaxation-times.pdf |
610ad0ed45805d722f80e4de | 10.26434/chemrxiv-2021-jz3zq | The Open Force Field Evaluator: An automated, efficient, and scalable framework for the estimation of physical properties from molecular simulation | Developing accurate classical force field representations of molecules is key to realizing the full potential of molecular simulations, both as a powerful route to gaining fundamental insight into a broad spectrum of chemical and biological phenomena, and for predicting physicochemical and mechanical properties of substances. The Open Force Field Consortium is an industry-funded open science effort to this end, developing open source tools for rapidly generating new, high-quality small molecule force fields. An integral aspect of this is the parameterization and assessment of force fields against high-quality, condensed phase physical property data, curated from open data sources such the NIST ThermoML Archive, alongside quantum chemical data. The quantity of such experimental data in open data archives alone would require an onerous amount of human and compute resources to both curate and estimate manually, especially when estimations must be made for numerous sets of force field parameters. Here we present an entirely automated, highly scalable framework for evaluating physical properties and their gradients in terms of force field parameters. It is written as a modular and extensible Python framework, which employs an intelligent multiscale estimation approach that allows for the automated estimation of properties from simulation and cached simulation data, and a pluggable API for estimation of new properties. In this study we demonstrate the utility of the framework by benchmarking the OpenFF 1.0.0 small molecule force field, GAFF 1.8 and GAFF 2.1 force fields against a test set of binary density and enthalpy of mixing measurements curated using the frameworks utilities. Further, we demonstrate the framework's utility as part of force field optimization by using it alongside ForceBalance, a framework for systematic force field optimization, to retrain a set of non-bonded van der Waals parameters against a training set of density and enthalpy of vaporization measurements. | Simon Boothroyd; Lee-Ping Wang; David Mobley; John Chodera; Michael Shirts | Theoretical and Computational Chemistry; Computational Chemistry and Modeling | CC BY 4.0 | CHEMRXIV | 2021-08-05 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/610ad0ed45805d722f80e4de/original/the-open-force-field-evaluator-an-automated-efficient-and-scalable-framework-for-the-estimation-of-physical-properties-from-molecular-simulation.pdf |
60c741b59abda2d0cdf8bee1 | 10.26434/chemrxiv.7436789.v3 | An Exploration Strategy Improves the Diversity of de novo Ligands Using Deep Reinforcement Learning – A Case for the Adenosine A2A Receptor | <p></p><p>Over the last five
years deep learning has progressed tremendously in both image recognition and
natural language processing. Now it is increasingly applied to other data rich
fields. In drug discovery, recurrent neural networks (RNNs) have been shown to
be an effective method to generate novel chemical structures in the form of
SMILES. However, ligands generated by current methods have so far provided relatively low
diversity and do not fully cover the whole chemical
space occupied by known ligands. Here, we propose a new method (DrugEx) to
discover <i>de novo</i> drug-like molecules.
DrugEx is an RNN model (generator) trained through reinforcement learning which
was integrated with a special exploration strategy. As a case study we applied
our method to design ligands against the adenosine A<sub>2A</sub> receptor.
From ChEMBL data, a machine learning model (predictor) was created to predict
whether generated molecules are active or not. Based on this predictor as the
reward function, the generator was trained by reinforcement learning without
any further data. We then compared the performance of our method with two
previously published methods, REINVENT and ORGANIC. We found that candidate
molecules our model designed, and predicted to be active, had a larger chemical
diversity, and better covered the chemical space of known ligands compared to
the state-of-the-art.</p><p></p> | Xuhan Liu; Kai Ye; Herman Van Vlijmen; Adriaan P. IJzerman; Gerard JP Van westen | Machine Learning; Artificial Intelligence; Chemoinformatics - Computational Chemistry | CC BY NC ND 4.0 | CHEMRXIV | 2019-04-16 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/60c741b59abda2d0cdf8bee1/original/an-exploration-strategy-improves-the-diversity-of-de-novo-ligands-using-deep-reinforcement-learning-a-case-for-the-adenosine-a2a-receptor.pdf |
60c751a3567dfe0f14ec5acf | 10.26434/chemrxiv.13194422.v1 | Mass Spectrometry Imaging of Diclofenac and Its Metabolites in Tissues Using Nanospray Desorption Electrospray Ionization. | <p>Glucuronidation is a common phase II metabolic process for
drugs and xenobiotics which increases their solubility for excretion. Acyl glucuronides
(glucuronides of carboxylic acids) present concerns of toxicity as they have
been implicated in gastrointestinal toxicity and hepatic failure. Despite the
substantial success in the bulk analysis of these species, little is known
about their localization in tissues. Herein,
we used nanospray desorption electrospray ionization mass spectrometry imaging
(nano-DESI-MSI) to examine the localization of diclofenac, a
widely used nonsteroidal anti-inflammatory drug, and its metabolites in mouse kidney and liver
tissues. Nano-DESI allows for label-free imaging with high spatial resolution and
sensitivity without special sample pretreatment. Using nano-DESI-MSI, ion
images for diclofenac and its major metabolites were produced. MSI data
acquired over a broad <i>m/z</i> range
showed fairly low signals of the drug and its metabolites. At least an order of
magnitude improvement in the signals was obtained using selected ion monitoring
(SIM), with <i>m/z</i> windows centered
around the low-abundance ions of interest. Using nano-DESI MSI in SIM mode, we
observed that diclofenac acyl glucuronide is localized to the inner medulla and
hydroxydiclofenac to the cortex of the kidney. The distributions observed for
both metabolites closely match the previously reported localization of enzymes
that process diclofenac into its respective metabolites. The localization of diclofenac
acyl glucuronide to medulla likely indicates that the toxic metabolite is being
excreted from the tissue. In contrast, a
uniform distribution of diclofenac, hydroxydiclofenac and the diclofenac acyl glucuronide
metabolite was observed in the liver tissue. Semiquantitative analysis found the
metabolite to diclofenac ratios calculated from nano-DESI in agreement to those
calculated from liquid chromatography tandem mass spectrometry (LC-MS/MS)
experiments. Collectively, our results demonstrate nano-DESI-MSI can be
successfully used to image diclofenac and its primary metabolites in dosed
liver and kidney tissues from mice and derive semi-quantitative data from
localized tissue regions. </p> | Hilary Brown; Daniela Mesa Sanchez; ruichuan yin; Bingming Chen; Marissa Vavrek; Mark Cancilla; Wendy Zhong; Baojen Shyong; Rena Zhang; Fangbiao Li; Julia Laskin | Imaging; Mass Spectrometry | CC BY NC ND 4.0 | CHEMRXIV | 2020-11-06 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/60c751a3567dfe0f14ec5acf/original/mass-spectrometry-imaging-of-diclofenac-and-its-metabolites-in-tissues-using-nanospray-desorption-electrospray-ionization.pdf |
64d45ad669bfb8925aad450a | 10.26434/chemrxiv-2023-8w46q-v3 | Determination of Ideal Conditions for the Production of Hydroxyl Radicals through Spectroscopy of Ferric Thiocyanate and Methyl Orange | Exposure to radiation can lead to the breakdown of water into reactive oxygen species (ROS), such as hydroxyl radicals (OH·), through a process called radiolysis. The presence of hydroxyl radicals (OH·) and other ROS can cause mutations to DNA in the human body. While hydrogen peroxide (H₂O₂), a product of radiolysis, may not be a strong ROS on its own, it can react with certain metal ions such as iron(II) to produce hydroxyl radicals in a process called the Fenton reaction. This study investigates the optimal conditions for the Fenton reaction using a cost-effective spectroscopic analysis of ferric thiocyanate and degradation of methyl orange to detect the presence of Fe3+ and OH·. Understanding conditions and methods of detection for the Fenton reaction is relevant due to the carcinogenic nature of the hydroxyl radicals produced [1]. The results of the spectroscopic analysis suggest that the Fenton reaction occurs ideally in acidic environments (p = 0.00354) with low temperature dependence. Additionally, both spectroscopic methods are effective for detecting the efficiency of Fenton processes. This study provides valuable insights for future research on the Fenton reaction and its potential applications. | Nirbaan Maken | Physical Chemistry; Analytical Chemistry; Analytical Chemistry - General; Solution Chemistry; Spectroscopy (Physical Chem.) | CC BY 4.0 | CHEMRXIV | 2023-08-10 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/64d45ad669bfb8925aad450a/original/determination-of-ideal-conditions-for-the-production-of-hydroxyl-radicals-through-spectroscopy-of-ferric-thiocyanate-and-methyl-orange.pdf |
622fce860350dd3f2cd87c2f | 10.26434/chemrxiv-2022-0kw6c-v2 | AI-based inverse design for electrochemically controlled microscopic gradients of O2 and H2O2 | A fundamental understanding of the extracellular microenvironments of O2 and reactive oxygen species (ROS) such as H2O2, ubiquitous in microbiology, demands high-throughput methods of mimicking, controlling, and perturbing gradients of O2 and H2O2 at microscopic scale with high spatiotemporal precision. However, there is a paucity for a high-throughput strategy of microenvironment design and it remains challenging to achieve O2 and H2O2 heterogeneities with the microbiologically desirable spatiotemporal resolutions. Here we report machine-learning-based inverse design of electrochemically generated microscopic O2 and H2O2 profiles that are relevant for microbiology. Microwire arrays with suitably designed electrochemical catalysts enable the independent control of O2 and H2O2 profiles with spatial resolution of ~101 μm and temporal resolution of ~100 sec. Neural networks aided by data augmentation inversely design the experimental conditions needed for targeted O2 and H2O2 microenvironments while being order-of-magnitude faster. Integrating artificial intelligence with electrochemically controlled concentration heterogeneity creates a viable fast-response platform towards better understanding the extracellular space with desirable spatiotemporal control. | Yi Chen; Jingyu Wang; Ben Hoar; Shengtao Lu; Xun Guan; Chong Liu | Inorganic Chemistry; Catalysis; Electrochemistry; Electrocatalysis; Materials Chemistry | CC BY NC ND 4.0 | CHEMRXIV | 2022-03-15 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/622fce860350dd3f2cd87c2f/original/ai-based-inverse-design-for-electrochemically-controlled-microscopic-gradients-of-o2-and-h2o2.pdf |
629a1d4e97e76ad380c4c36e | 10.26434/chemrxiv-2022-9vnch | Dissecting the heterogeneous glycan profiles of recombinant coronavirus spike proteins with individual ion mass spectrometry | Surface-embedded glycoproteins, such as the spike protein trimers of coronaviruses MERS, SARS-CoV, and SARS-CoV-2 play a key role in viral function and are the target antigen for many vaccines. However, their significant glycan heterogeneity poses an analytical challenge. Here, we have utilized individual ion mass spectrometry (I2MS), a form of charge detection mass spectrometry (CDMS) that uses a commercially available Orbitrap analyzer, to directly produce heterogeneous glycan mass profiles of these three coronavirus spike protein trimers under native-like conditions. Analysis by I2MS shows that glycosylation contributes to the molecular mass of each protein trimer more significantly than expected by bottom-up techniques. This highlights the importance of obtaining complementary intact mass information when characterizing glycosylation of such heterogeneous proteins. Enzymatic dissection to remove sialic acid or N-linked glycans demonstrates that I2MS can be used to better understand the glycan profile from a native viewpoint. Deglycosylation of N-glycans followed by I2MS indicates that the SARS-CoV-2 spike protein trimer contains glycans that are more difficult to remove than its MERS and SARS-CoV counterparts and differences in glycan removal are correlated with solvent accessibility. I2MS technology enables characterization of protein mass and intact glycan profile and is orthogonal to traditional protein mass analysis methods such as size exclusion chromatography-multiple angle light scattering (SEC-MALS) and field flow fractionation-multiple angle light scattering (FFF-MALS). An added advantage of I2MS is low sample use, requiring 100-fold less than other methodologies. This work highlights how I2MS technology can enable efficient development of vaccines and therapeutics for pharmaceutical development. | Alyssa Q. Stiving; David J. Foreman; Zachary L. VanAernum; Eberhard Durr; Shiyi Wang; Josef Vlasak; Jennifer Galli; Jared O. Kafader; Xuanwen Li; Hillary Schuessler; Douglas Richardson | Analytical Chemistry; Mass Spectrometry; Separation Science | CC BY NC ND 4.0 | CHEMRXIV | 2022-06-08 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/629a1d4e97e76ad380c4c36e/original/dissecting-the-heterogeneous-glycan-profiles-of-recombinant-coronavirus-spike-proteins-with-individual-ion-mass-spectrometry.pdf |
6363dfd51db0bd32df455114 | 10.26434/chemrxiv-2022-lk587-v2 | Interfacial Engineering of Fluoropolymers Towards Higher Piezoelectric, Ferroelectric, and Dielectric Performance for Sensing and Energy Harvesting Applications | The electrical properties of pristine fluoropolymers are inferior due to their low polar crystalline phase content and rigid dipoles that tend to retain their fixed moment and orientation. Several strategies such as electrospinning, electrohydrodynamic pulling, and template-assisted growing have been proven to enhance the electrical properties of fluoropolymers, however, these techniques are mostly very hard to scale-up and expensive. Here, we propose a facile interfacial engineering approach based on amine-functionalized graphene oxide (AGO) to manipulate the intermolecular interactions in poly (vinylidenefluoride-trifluoroethylene) (PVDF-TrFE) to induce β-phase formation, enlarge the lamellae dimensions, and align the micro-dipoles. The coexistence of primary amine and hydroxyl groups on AGO nanosheets offers strong hydrogen bonding with fluorine atoms, which facilitates domain alignment, resulting in an exceptional remnant polarization of 11.3 µC cm-2. PVDF-TrFE films with 0.1 wt% AGO demonstrated voltage coefficient, energy density, and energy-harvesting figure of merit values of 0.30 Vm N-1, 4.75 J cm-3, and 14 pm3 J-1, respectively, making it outstanding compared with state-of-the-art ceramic-free ferroelectric films. We believe this work can open-up new insights towards structural and morphological tailoring of fluoropolymers to enhance their electrical and electromechanical performance and pave the way for their industrial deployment in next-generation wearables and human-machine interfaces. | Hamed Abdolmaleki; Astri Bjørnetun Haugen; Kristian Birk Buhl; Kim Daasbjerg; Shweta Agarwala | Materials Science; Composites | CC BY NC ND 4.0 | CHEMRXIV | 2022-11-04 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/6363dfd51db0bd32df455114/original/interfacial-engineering-of-fluoropolymers-towards-higher-piezoelectric-ferroelectric-and-dielectric-performance-for-sensing-and-energy-harvesting-applications.pdf |
64f0676979853bbd78c916f0 | 10.26434/chemrxiv-2023-6k06s |
Effects of Surface Chemistry on the Mechanochemical
Decomposition of Lubricant Additives | The growth of protective tribofilms from lubricant antiwear additives on rubbing surfaces is initiated by mechanochemical decomposition reactions. These processes are not well understood at the molecular scale for many important additives, such as tricresyl phosphate (TCP). One aspect that needs further clarification is the extent to which the surface properties affect the mechanochemical decomposition rate. In this study, we use nonequilibrium molecular dynamics (NEMD) simulations with a reactive force field (ReaxFF) to study the decomposition of TCP molecules confined and pressurised
between sliding ferrous surfaces at a range of temperatures. We compare the decomposition of TCP
on native iron, iron carbide, and iron oxide surfaces. We show that the decomposition rate of TCP molecules increases exponentially with temperature and shear stress, implying that this is a stress-augmented thermally activated process. The rates and products of decomposition depend on the properties of the confining surfaces. The activation energy, activation volume, and pre-exponential factor are similar for TCP decomposition between iron and iron carbide surfaces, but significantly different for iron oxide surfaces. These findings provide new insights into the mechanochemical decomposition of TCP and have important implications for the design of novel lubricant additives for use in high-temperature and high-pressure environments' | Egheosa Ogbomo; Fakhrul H. Bhuiyan; Carlos Ayestaran Latorre; Ashlie Martini; James Ewen | Theoretical and Computational Chemistry; Computational Chemistry and Modeling | CC BY 4.0 | CHEMRXIV | 2023-09-26 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/64f0676979853bbd78c916f0/original/effects-of-surface-chemistry-on-the-mechanochemical-decomposition-of-lubricant-additives.pdf |
624b09ae855ee52ca0e1f566 | 10.26434/chemrxiv-2022-9n05p-v2 | Proton-coupled Electron Transfer in a Ruthenium (II) Bipyrimidine Complex in its Ground and Excited Electronic States | Proton-coupled electron transfer (PCET) was studied for the ground and excited electronic states of a [Ru(terpy)(bpm)(OH2)(PF6)] complex, Ru-bpm. Cyclic voltammetry measurements show that the Ru(II)-aqua moiety undergoes PCET to form Ru(IV)-oxo moiety in the anodic region, while the bpm ligand undergoes PCET to form bpmH2 in the anodic region. The photophysical behavior of Ru-bpm was studied using steady-state and femtosecond transient UV-vis absorption spectroscopy, coupled with density functional theory (DFT) calculations. The lowest-lying excited state of Ru-bpm is described as a (Ru bpm) metal-to-ligand charge transfer (MLCT) state, while the metal-centered (MC) excited state was found computationally to be close in energy to the lowest-energy bright MLCT state (MC state was 0.16 eV above the MLCT state). The excited state kinetics of Ru-bpm were found via transient absorption spectroscopy to be short-lived and were fit well to a biexponential function with lifetimes 1=4 ps and 2=65 ps in aqueous solution. Kinetic isotope effect of 1.75 was observed for both decay components, indicating that the solvent plays an important role in the excited-state dynamics of Ru-bpm. Based on the pH-dependent studies and the results from prior studies of similar Ru-complexes, we hypothesize that the 3MLCT state forms an excited-state hydrogen-bond adduct with the solvent molecules and that this process occurs with the 4 ps lifetime. The formation of such hydrogen-bond complex is consistent with the electronic density accumulation at the peripheral N atoms of the bpm moiety in the 3MLCT state. The hydrogen-bonded state 3MLCT’ decays to the ground state with a 65 ps lifetime. Such short lifetime is likely associated with the efficient vibrational energy transfer from 3MLCT state to the solvent. | Matthew Drummer; Ravindra Weerasooriya; Nikita Gupta; Erik Askins; Xiaolin Liu; Andrew Valentine; Xiaosong Li; Ksenija Glusac | Physical Chemistry; Photochemistry (Physical Chem.); Physical and Chemical Processes; Spectroscopy (Physical Chem.) | CC BY 4.0 | CHEMRXIV | 2022-04-05 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/624b09ae855ee52ca0e1f566/original/proton-coupled-electron-transfer-in-a-ruthenium-ii-bipyrimidine-complex-in-its-ground-and-excited-electronic-states.pdf |
627bd500d555503bb896a096 | 10.26434/chemrxiv-2022-2x0b1 | Total Synthesis and Prediction of Ulodione Natural Products Guided by DFT Calculations. | A biomimetic synthetic strategy has resulted in a 2-step total synthesis of (±)-ulodione A and the prediction of two potential natural products, (±)-ulodiones C and D. This work was guided by computational investigations into the selectivity of a proposed biosynthetic Diels–Alder dimerization, which was then utilized in the chemical synthesis. This work highlights how biosynthetic considerations can both guide the design of efficient synthetic strategies and lead to the anticipation of new natural products. | Jacob Bestwick; David Jones; Helen Jones; Panagiotis Kalomenopoulos; Rafal Szabla; Andrew Lawrence | Theoretical and Computational Chemistry; Organic Chemistry; Natural Products; Organic Synthesis and Reactions; Computational Chemistry and Modeling | CC BY NC ND 4.0 | CHEMRXIV | 2022-05-12 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/627bd500d555503bb896a096/original/total-synthesis-and-prediction-of-ulodione-natural-products-guided-by-dft-calculations.pdf |
640022e3897b18336f59c7b5 | 10.26434/chemrxiv-2023-63gsc | Practical Synthesis of Dendritic Hyperbranched Polyacrylates and Their Topological Block Polymers by Organotellurium-Mediated Emulsion Polymerization in Water | The practical synthesis of structurally controlled hyperbranched polymers (HBPs) by organotellurium-mediated radical polymerization (TERP) in emulsions is reported. Copolymerization of vinyltelluride, which induces controlled branch structure and is named evolmer, and acrylates in the presence of TERP chain transfer agent (CTA) in water afforded HBPs having den-dron structure. The structure of the HBPs, i.e., molecular weight, dispersity, branch number, and branch length (the number of monomer units between branch points), were controlled by changing the amount of CTA, evolmer, and acrylate monomers, and HB-poly(butyl acrylate)s (HBPBAs) with up to the 8th generation having an average of 255 branches were successfully synthe-sized. As the monomer conversion reached nearly quantitative and the obtained polymer particles were well dispersed in water, the method is highly suitable for the synthesis of topological block polymers, block polymers consisting of different topologies. Thus, linear-block-HB, HB-block-linear, and HB-block-HB-PBAs with the controlled structure were successfully synthesized just by adding the second monomer(s) to the macro-CTA. The intrinsic viscosity of the resulting homo- and topological block PBAs was systematically controlled by the degree of the branch, the branch length, and the topology. Therefore, the method opens the possibility of obtaining various HBPs with diverse branch structures and tuning the polymer properties by the pol-ymer topology. | Shigeru Yamago; Yuhan Jiang; Masato Kibune; Masatoshi Tosaka | Polymer Science; Polymerization (Polymers) | CC BY NC ND 4.0 | CHEMRXIV | 2023-03-03 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/640022e3897b18336f59c7b5/original/practical-synthesis-of-dendritic-hyperbranched-polyacrylates-and-their-topological-block-polymers-by-organotellurium-mediated-emulsion-polymerization-in-water.pdf |
60c742f54c89196282ad258a | 10.26434/chemrxiv.8867651.v1 | Fast Ring-Opening of an Intermediary α-Stannyl-β-Cyclopropylvinyl Radical Does Not Support Formation of an α-Stannylvinyl Cation in the O-Directed Free Radical Hydrostannation of Dialkyl Acetylenes | O-Directed free radical hydrostannation of a β-cyclopropyl propargylic
alcohol probe with stannanes and cat. Et<sub>3</sub>B in THF/H<sub>2</sub>O, or
PhMe/MeOH, failed to deliver any detectable products of α-stannylvinyl cation capture.
Instead only α-stannyl-β-cyclopropylvinyl radical
intermediates could be detected, which underwent fast H-atom abstraction and/or cyclopropane
ring-opening as a result of fast eliminative β-scission. These outcomes strongly rule against the claimed intermediacy of α-stannylvinyl cations in the O-directed free radical hydrostannation of disubstituted acetylenes, and provide further good supporting evidence for such reactions proceeding by an exclusively free radical O-coordinatively-controlled mechanism. | Hamish A. Watson; Soraya Manaviazar; Hannah G. Steeds; Karl Hale | Organic Synthesis and Reactions | CC BY NC ND 4.0 | CHEMRXIV | 2019-07-15 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/60c742f54c89196282ad258a/original/fast-ring-opening-of-an-intermediary-stannyl-cyclopropylvinyl-radical-does-not-support-formation-of-an-stannylvinyl-cation-in-the-o-directed-free-radical-hydrostannation-of-dialkyl-acetylenes.pdf |
60d0bcf1b361524289011c30 | 10.26434/chemrxiv-2021-vcs1x-v2 | Design of Long-Term Stable Concentrated Colloidal Dispersions in Ionic Liquids up to 473 K | Some of the most promising fields of application of ionic liquid-based colloids imply elevated temperatures. Their careful design and analysis is therefore essential. The system studied are iron oxide nanoparticles (NPs) dispersed in ethyl-methylimidazolium bistriflimide (EMIM TFSI). The key parameters of the solid-liquid interface, tuned at room temperature, are the surface charge density and the nature of the counterions. The thermal stability of these nanoparticle dispersions is then analysed on the short and long term up to 473 K. A multiscale analysis is performed combining dynamic light scattering (DLS), small angle X-ray/neutron scattering (SAXS/SANS) and thermogravimetric analysis (TGA). With a careful choice of the species at the solid-liquid interface, ionic liquid-based colloidal dispersions of iron oxide NPs in EMIM TFSI stable over years at room temperature can be obtained, also stable at least over days up to 473 K and NPs concentrations up to 12 vol% (30 wt%). | Jesse Cornelius Riedl; Mitradeep Sarkar; Thiago Fiuza; Fabrice Cousin; Jérome Depeyrot; Emmanuelle DUBOIS; Guillaume Mériguet; Régine Perzynski; Véronique Peyre | Physical Chemistry; Nanoscience; Interfaces; Physical and Chemical Properties; Structure; Materials Chemistry | CC BY NC ND 4.0 | CHEMRXIV | 2021-06-22 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/60d0bcf1b361524289011c30/original/design-of-long-term-stable-concentrated-colloidal-dispersions-in-ionic-liquids-up-to-473-k.pdf |
62d6aeef4e76bf4b8f963311 | 10.26434/chemrxiv-2022-2k8g5-v2 | Homogeneous ice nucleation rates for mW and TIP4P/ICE models through Lattice Mold calculations | Water freezing is the most common liquid-to-crystal phase transition on Earth, however, despite its critical implications on climate change and cryopreservation among other disciplines, its characterization through experimental and computational techniques remains elusive. In this work, we make use of computer simulations to measure the nucleation rate (J) of water at normal pressure under different supercooling conditions, ranging from 215 to 240K. We employ two different water models, mW, a coarse-grained potential for water, and TIP4P/ICE, an atomistic non-polarizable water model that provides one of the most accurate representations of the different ice phases. To evaluate J, we apply the Lattice Mold technique, a computational method based on the use of molds to induce the nucleus formation from the metastable liquid under conditions at which observing spontaneous nucleation would be unfeasible. With this method, we obtain estimates of the nucleation rate for ice Ih, Ic and a stacking mixture of ice Ih/Ic; reaching consensus with most of the previously reported rates, although differing with some others. Furthermore, we confirm that the predicted nucleation rates by the TIP4P/ICE model are in better agreement with experimental data than those obtained through the mW potential. Taken together, our study provides a reliable methodology to measure nucleation rates in a simple and computationally efficient manner which contributes to benchmarking the freezing behaviour of two popular water models. | Ignacio Sanchez-Burgos; Andres R. Tejedor; Carlos Vega; Maria M. Conde; Eduardo Sanz; Jorge Ramirez; JORGE R. ESPINOSA | Theoretical and Computational Chemistry; Physical Chemistry; Computational Chemistry and Modeling; Interfaces; Thermodynamics (Physical Chem.) | CC BY NC ND 4.0 | CHEMRXIV | 2022-07-21 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/62d6aeef4e76bf4b8f963311/original/homogeneous-ice-nucleation-rates-for-m-w-and-tip4p-ice-models-through-lattice-mold-calculations.pdf |
60c7537bbb8c1a2c613dc064 | 10.26434/chemrxiv.13498704.v1 | Formulation and Implementation of Density Functional Embedding Theory using Products of Basis Functions | The representation of embedding potential in using products of AO basis functions
has been developed in the context of density functional embedding theory (DFET).
The formalism allows to treat pseudopotential and all-electron calculations on the same
footing and enables simple transfer of the embedding potential in the compact matrix
form. In addition, a simple cost-reduction procedure for basis set and potential reduction has been proposed. The theory has been implemented for the condensed-phase
and molecular systems using Gaussian and Plane Waves (GPW) and Gaussian and
Augmented Plane Waves (GAPW) formalisms and tested for proton transfer reactions
in the cluster and the condensed phase. The computational scaling of the embedding
potential optimization is similar to this of hybrid DFT with a significantly reduced
prefactor and allows for large-scale applications.<div><br /></div> | Vladimir Rybkin | Computational Chemistry and Modeling; Theory - Computational | CC BY NC ND 4.0 | CHEMRXIV | 2020-12-30 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/60c7537bbb8c1a2c613dc064/original/formulation-and-implementation-of-density-functional-embedding-theory-using-products-of-basis-functions.pdf |
60c751619abda2f492f8dbdf | 10.26434/chemrxiv.13152953.v1 | Enhanced Photoelectrocatalysis Using a Bimetallic Plasmonic Near-Perfect Absorber | In this paper, we developed the fabrication of a plasmonic near-perfect absorber with a dense, uniform monolayer of AuPd alloyed nanoparticles as the absorbing layer. The nanoparticles were prepared by dewetting thin films (<4 nm) of each metal on a dielectric surface and extensive characterization confirmed the lack of other bimetallic phases. Plasmonic near-perfect absorbers containing an alloyed nanoparticle layer demonstrated both strong on-resonance absorption of incident light (up to 97%) and an improved photocatalytic response, compared to either monometallic derivative, for the photoelectrochemical reduction of water.<br /> | Qi Xiao; CALUM KINNEAR; Timothy
U. Connell; Muhammad Kalim Kashif; Christopher D. Easton; Aaron Seeber; Laure Bourgeois; Gus O. Bonin; Noel W. Duffy; Anthony S. R. Chesman; Daniel E. Gómez | Alloys; Metamaterials; Nanostructured Materials - Materials; Thin Films; Nanocatalysis - Catalysts & Materials; Plasmonic and Photonic Structures and Devices; Photochemistry (Physical Chem.) | CC BY NC ND 4.0 | CHEMRXIV | 2020-10-29 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/60c751619abda2f492f8dbdf/original/enhanced-photoelectrocatalysis-using-a-bimetallic-plasmonic-near-perfect-absorber.pdf |
63cabc6310cb6a2c7ae05fa6 | 10.26434/chemrxiv-2023-lrg06 | Competitive Isomerization and Catalyst Decomposition During Ring-Closing Metathesis | Ring-closing metathesis (RCM) is an elegant means of forming cyclic structural elements in both simple and complex molecules. Mechanistically, the reaction cycle is well understood, though subtle details concerning the fate of the catalyst and the appearance of yield-reducing by-products remain to be fully deciphered. We applied real-time analysis using electrospray ionization mass spectrometry (ESI-MS) to probe the RCM reaction, including studying the dynamics of all charged species in the reaction mixture and investigating the nature of the by-products formed. The catalyst of choice was Grubbs’ second-generation catalyst. The principal findings included the fact that for slower reactions, by-products appeared that differed in mass from the starting material and product by increments of CH2; that isomerization reactions were responsible for these by-products; and that the catalyst decomposes to form charged products including [ClPCy3]+, [HPCy3]+, and the imidazolinium salt of the N-heterocyclic carbene (NHC) ligand. In cases where RCM is slow, isomerization reactions play a disproportionate part in affecting yield of the desired product. | Charles Killeen; Jie Liu; Harmen Zijlstra; Florian Maass; James Piers; Reid Adams; Allen G. Oliver; J. Scott McIndoe | Inorganic Chemistry; Catalysis; Organometallic Chemistry; Homogeneous Catalysis; Kinetics and Mechanism - Organometallic Reactions | CC BY NC ND 4.0 | CHEMRXIV | 2023-01-25 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/63cabc6310cb6a2c7ae05fa6/original/competitive-isomerization-and-catalyst-decomposition-during-ring-closing-metathesis.pdf |
66b2533a5101a2ffa845e974 | 10.26434/chemrxiv-2024-lbswf | Late-stage functionalization using a popular titrating agent: aryl- chlorides and -fluorides activation by the diphenylacetic acid dianion | Aryl-chlorides and -fluorides are common building blocks, but their use in synthesis is limited by the high stability of their Ar-X bonds. The generation of aryl radicals via activation of strong Ar-X bonds is possible through the irradiation of tailor-made organic anions, which become reductants stronger than lithium metal. We report that the combination of visible light with the cheap diphenylacetic acid dianion is an even better tool, showing excellent activity across a variety of complex substrates and providing opportunities for late-stage drug modification. Ar-X bonds are chemoselectively activated in the presence of more easily reducible functions, such as Alk-Cl ones and carbonyl groups, reminding the Marcus inverted region principle. These results pave the way to original synthetic strategies that would be otherwise considered impossible | Alessandro Cerveri; Giulia Russo; Sara Sparascio; Daniele Merli; Raimondo Maggi; Nicola Della Ca'; Matteo Lanzi; Giovanni Maestri | Organic Chemistry; Organic Compounds and Functional Groups; Organic Synthesis and Reactions; Photochemistry (Org.) | CC BY NC 4.0 | CHEMRXIV | 2024-08-08 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/66b2533a5101a2ffa845e974/original/late-stage-functionalization-using-a-popular-titrating-agent-aryl-chlorides-and-fluorides-activation-by-the-diphenylacetic-acid-dianion.pdf |
632a22d9975e946232826064 | 10.26434/chemrxiv-2022-cktrh | Why PEDOT:PSS Should Not Be Used for Raman Sensing of Redox States (and How It Could Be) | Here we investigated the rationale of this approach through systematic experiments, in which the Raman spectrum of PEDOT:PSS was analyzed in the presence of either non-oxidizing and oxidizing electrolytes. The results demonstrated that Raman spectra precisely reflect the conformation of PEDOT units and their interactions with PSS. Two different responses were observed. In the case of oxidizing electrolytes, the effect of charge transfer is accurately transduced in Raman spectrum changes. On the other hand, reduction induces a progressive separation between the PEDOT and PSS chains, which decreases their mutual interaction. This stimulus determines characteristic variations in intensity, shape and position of the Raman spectra. However, we demonstrated that the same effects can be obtained either by increasing the concentration of non-oxidizing electrolytes or by deprotonating PSS chains. This poses severe limitations to the use of PEDOT:PSS for this type of Raman sensing. This study allows to revise most of the Raman results reported in literature with a clear model, setting a new basis for investigating the dynamics of mixed electronic/ionic charge transfer in conductive polymers. | Ivano Alessandri; Fabrizio Torricelli; Beatrice Cerea; Michele Speziani; Paolo Romele; Irene Vassalini | Physical Chemistry; Analytical Chemistry; Spectroscopy (Anal. Chem.); Physical and Chemical Properties; Spectroscopy (Physical Chem.); Materials Chemistry | CC BY NC ND 4.0 | CHEMRXIV | 2022-09-21 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/632a22d9975e946232826064/original/why-pedot-pss-should-not-be-used-for-raman-sensing-of-redox-states-and-how-it-could-be.pdf |
643660ab73c6563f14b45aee | 10.26434/chemrxiv-2023-bx28l | Functional Dithienopyrazines – Structure-Property Relationships | Dithienopyrazines are only scarcly used as building blocks in organic electronic materials. Here, we report efficient preparation and investigation of syn- and anti-dithienopyrazines, which were functionalized with triaraylamine units to provide different series of donor-acceptor-donor-type materials. The characterization of the optoelectronic properties resulted in valuable structure-property relationships and allowed for the elucidation of the influence of structural effects such as core structure (syn vs anti), type of substituents (directly arylated vs ethynylated aryl), and substitution pattern (a,a‘- vs ß,ß‘- vs fourfold substitution). Finally, first application of a dithienopyrazine derivative as model for hole-transport materials tailored for organic electronic devices has been realized. | Peter Baeuerle; Elena Mena-Osteritz; Franziska Kreuzer | Organic Chemistry; Organic Synthesis and Reactions | CC BY NC ND 4.0 | CHEMRXIV | 2023-04-12 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/643660ab73c6563f14b45aee/original/functional-dithienopyrazines-structure-property-relationships.pdf |
6564dfea29a13c4d471fb67a | 10.26434/chemrxiv-2023-vxrr9 | Structure-based design of a potent and selective YTHDC1 ligand | N6-Adenosine methylation (m6A) is a prevalent post-transcriptional modification of mRNA, with YTHDC1 being the reader protein responsible for recognizing this modification in the nucleus of the cell. Here we present a protein structure-based medicinal chemistry campaign that resulted in the YTHDC1 inhibitor 40 which shows an equilibrium dissociation constant (Kd) of 49 nM. The crystal structure of the complex (1.6-Å resolution) validated the design. Compound 40 is selective against the cytoplasmic m6A-RNA readers YTHDF1-3 and YTHDC2 and shows antiproliferative activity against the acute myeloid leukemia (AML) cell lines THP-1, MOLM-13, and NOMO1. For the series of compounds that culminated into ligand 40, the good correlation between the affinity in the biochemical assay and antiproliferative activity in the cellular assay (THP-1) provides evidence of YTHDC1 target engagement in the cell. Thus compound 40 meets chemical probe properties for studying the role of YTHDC1 in AML. | František Zálešák; Francesco Nai; Rajiv K. Bedi; Yaozong Li; Marcin Herok; Elena Bochenkova; Francesco Errani; Amedeo Caflisch | Biological and Medicinal Chemistry; Organic Chemistry; Bioorganic Chemistry; Drug Discovery and Drug Delivery Systems | CC BY NC ND 4.0 | CHEMRXIV | 2023-11-29 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/6564dfea29a13c4d471fb67a/original/structure-based-design-of-a-potent-and-selective-ythdc1-ligand.pdf |
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