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66d160c3f3f4b0529099531f | 10.26434/chemrxiv-2024-wfqmg-v2 | Developing Force Fields for Accurate Mg2+ and Triphosphate Interactions in ATP∙Mg2+ and GTP∙Mg2+ Complexes | In cells, adenosine triphosphate (ATP) and guanosine triphosphate (GTP) molecules typically form tri-coordinated or bi-coordinated ATP∙Mg2+ or GTP∙Mg2+ complexes with Mg2+ ions and bind to proteins, participating in and regulating many important cellular functions. The accuracy of their force field parameters plays a crucial role in studying the function-related conformations of ATP∙Mg2+ or GTP∙Mg2+ using molecular dynamics (MD) simulations. The parameters developed based on the methyl triphosphate model in existing AMBER force fields cannot accurately describe the conformational distribution of tri-coordinated or bi-coordinated ATP∙Mg2+ or GTP∙Mg2+ complexes in solution. In this study, we develop force field parameters for the triphosphate group based on the new ribosyl triphosphate model, considering the dihedral coupling effect, accurate van der Waals (vdW) interactions, and the influence of strongly polarized charges on conformational balance. The new force fields can accurately describe the conformational balance of tri-coordinated and bi-coordinated ATP∙Mg2+ or GTP∙Mg2+ conformations in solution and can be applied to simulate biological systems containing ATP∙Mg2+ or GTP∙Mg2+ complexes. | Fangchen Hu; Yuwei Zhang; Pengfei Li; Ruibo Wu; Fei Xia | Theoretical and Computational Chemistry; Theory - Computational | CC BY NC ND 4.0 | CHEMRXIV | 2024-08-30 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/66d160c3f3f4b0529099531f/original/developing-force-fields-for-accurate-mg2-and-triphosphate-interactions-in-atp-mg2-and-gtp-mg2-complexes.pdf |
60c74aae469df499cff43db7 | 10.26434/chemrxiv.12237995.v1 | Computational Molecular Docking and Virtual Screening Revealed Promising SARS-CoV-2 Drugs | The pandemic of novel coronavirus disease 2019 (COVID-19) is rampaging the world with more than 1.4 million of confirmed cases and more than 85,000 of deaths across world by April 9th, 2020. There is an urgent need to identify effective drugs to fight against the virus. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) belongs to the family of coronaviruses consisting of four structural and 16 non-structured proteins. Three non-structural proteins such as main protease, papain like protease, and RNA-dependent RNA polymerase are believed to play a crucial role in the virus replication. We applied a computational ligand-receptor binding modeling and performed a comprehensive virtual screening on the FDA-approved drugs against these three SARS-CoV-2 proteins using AutoDock Vina. Our computational studies indicated that Simeprevir, Ledipasvir, Idarubicin, Saquinavir, Ledipasivir, Partitaprevir, Glecaprevir, and Velpatasvir are all promising inhibitors, which displayed a lower binding energy (higher inhibitory effect) than Remdesivir, Lopinavir, and Ritonavir. However, we found that chloroquine and hydroxychloroquine, which showed efficacy in treating the COVID-19 in recent clinical studies, had high binding energy with all three proteins, suggesting they may work through a different mechanism. We also identified several novel drugs as potential inhibitors against SARS-CoV-2, including antiviral Raltegravir; antidiabetic Amaryl; antibiotics Retapamulin, Rifimixin, and Rifabutin; antiemetic Fosaprepitant and Netupitant. In summary, our computational molecular docking approach and virtual screening identified some promising candidate SARS-CoV-2 drugs that may be considered for further clinical studies. | Maryam Hosseini; Wanqiu Chen; Charles Wang | Bioinformatics and Computational Biology | CC BY NC ND 4.0 | CHEMRXIV | 2020-05-06 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/60c74aae469df499cff43db7/original/computational-molecular-docking-and-virtual-screening-revealed-promising-sars-co-v-2-drugs.pdf |
65b2956ae9ebbb4db9f9e7dc | 10.26434/chemrxiv-2024-vqfc1 | Cofactor-free biocatalytic hydrogenation of nitro compounds for synthesis of amines | We report a new paradigm for chemoselective hydrogenation of nitro compounds to amines, under mild, aqueous conditions. Hydrogenase enzyme releases electrons from H2 to a carbon black support which facilitates nitro-group reduction. For 30 nitroarenes we demonstrate full conversion (isolated yields 78 – 96%), with products including pharmaceuticals benzocaine, procainamide and mesalazine, and 4-aminophenol – precursor to acetaminophen (paracetamol). We also showcase gram-scale synthesis of procainamide with 90% isolated yield. We demonstrate potential for extension to aliphatic substrates. The catalyst is highly selective for reduction of the nitro group over other unsaturated bonds, tolerant to a wide range of functional groups, and exhibits excellent stability in reactions lasting up to 72 hours and full reusability over 5 cycles, indicating scope for direct translation to fine chemical manufacturing. | Daria Sokolova; Tara Lurshay; Jack Rowbotham; Georgia Stonadge; Holly Reeve; Sarah Cleary; Tim Sudmeier; Kylie Vincent | Biological and Medicinal Chemistry; Organic Chemistry; Catalysis; Organic Synthesis and Reactions; Biocatalysis; Heterogeneous Catalysis | CC BY NC 4.0 | CHEMRXIV | 2024-01-29 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/65b2956ae9ebbb4db9f9e7dc/original/cofactor-free-biocatalytic-hydrogenation-of-nitro-compounds-for-synthesis-of-amines.pdf |
67ab2bb76dde43c908621abf | 10.26434/chemrxiv-2025-bkwp1 | Impact of octahedral aluminium sites on guest molecule adsorption in zeolites: A computational study of 5-fluorouracil in zeolite FAU | Many aluminosilicate zeolites contain octahedral aluminium sites, which may occur as extra-framework or framework-associated sites. Due to the Lewis acidity of these sites, their impact on catalytic properties has been investigated frequently. Comparatively less emphasis has been placed on their role in adsorption, despite evidence for an irreversible binding of some guest molecules like the anticancer drug 5-fluorouracil (5-FU) to octahedral Al atoms. In the present study, dispersion-corrected density functional theory (DFT) calculations and DFT-based ab initio molecular dynamics simulations (AIMD) are employed to investigate the adsorption of 5-FU at a framework-associated octahedral Al site in zeolite FAU. The calculations show that 5-FU remains coordinated to the Al atom at room temperature and in the presence of water. In contrast, 5-FU molecules adsorbed at framework protons are quickly displaced by water molecules. It is thus demonstrated that octahedral Al atoms will negatively affect the release of 5-FU from zeolite hosts in drug delivery applications. A comparison of DFT-calculated infrared (IR) spectra to literature data provides evidence that Al-coordinated 5 FU molecules were indeed present in previously investigated samples. | Michael Fischer | Theoretical and Computational Chemistry; Physical Chemistry; Computational Chemistry and Modeling; Physical and Chemical Processes; Materials Chemistry; Crystallography | CC BY 4.0 | CHEMRXIV | 2025-02-13 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/67ab2bb76dde43c908621abf/original/impact-of-octahedral-aluminium-sites-on-guest-molecule-adsorption-in-zeolites-a-computational-study-of-5-fluorouracil-in-zeolite-fau.pdf |
62bb2624be884b46c3f343e5 | 10.26434/chemrxiv-2022-lw86k-v2 | Predicting clinical trial outcomes using drug bioactivities through graph database integration and machine learning | The ability to estimate the probability of a drug to receive approval in clinical trials provides natural
advantages to optimizing pharmaceutical research workflows. Success rates of clinical trials have deep
implications to costs, duration of development, and under pressure due to stringent regulatory approval
processes. We propose a machine learning approach that can predict the outcome of the trial with reliable
accuracies, using biological activities, physicochemical properties of the compounds, target-related
features, and NLP-based compound representation. Biological activities have never been used as a
predictive feature. We have extracted the drug-disease pair from clinical trials and mapped target(s) to that
pair using multiple data sources. Empirical results demonstrate that ensemble learning outperforms
independently trained, small-data ML models. We report results and inferences derived from a Random
forest classifier with an average accuracy of 93%, and an F1 score of 0.96 for the 'Pass' class. 'Pass' refers
to one of the two classes (Pass/ Fail) of all clinical trials and the model performed well in predicting the
'Pass' category. An analysis of the features demonstrates that bioactivity plays an important role in
predicting the outcome of a clinical trial. A significant effort has gone into the production of the dataset
that, for the first time, integrates clinical trial information with protein targets. All code to map these entities
is available through this study, and all data are from publicly available sources. While our model identifies
low-lying inferences when biological activities are included, the code to integrate biological activity and
target information provide researchers with access to deep curated and proprietary clinical trial databases
the ability to get deeper insights, better statistical significance, and capabilities to better predict trial
failures. | Vidhya Murali; Pradyumna Y Muralidhar; Cassandra Königs; Meera Nair; Sethulekshmi Madhu; Prema Nedungadi ; Gowri Srinivasa; Prashanth Athri | Theoretical and Computational Chemistry; Biological and Medicinal Chemistry; Bioinformatics and Computational Biology; Drug Discovery and Drug Delivery Systems; Machine Learning | CC BY 4.0 | CHEMRXIV | 2022-06-29 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/62bb2624be884b46c3f343e5/original/predicting-clinical-trial-outcomes-using-drug-bioactivities-through-graph-database-integration-and-machine-learning.pdf |
67bc6a7cfa469535b9b7454e | 10.26434/chemrxiv-2025-qmdhg | An Approach to Alkyl Azetidines for Medicinal Chemistry | Alkyl azetidines have been prepared by photochemical modifications of azetidine-2-carboxylic
acids in batch and in flow. The reaction has been realized in mg-, g-, and even multigram quantities. The
obtained azetidines are valuable building blocks for drug discovery. | Oleksandr Datsenko; Andrii Baziievskyi; Iryna Sadkova; Bismarck Campos; James Brewster II; John Kowalski; Ronald Hinklin; Pavel Mykhailiuk | Biological and Medicinal Chemistry; Organic Chemistry | CC BY 4.0 | CHEMRXIV | 2025-02-25 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/67bc6a7cfa469535b9b7454e/original/an-approach-to-alkyl-azetidines-for-medicinal-chemistry.pdf |
60c74d074c891945b9ad3744 | 10.26434/chemrxiv.12561965.v1 | Rational Design of Donor Acceptor Based Semiconducting Copolymers with High Dielectric Constant | <div>
<div>
<div>
<p>An efficient photogeneration of free charge carriers has long been recognized as the
paramount challenge in organic photovoltaic (OPV) devices. The low dielectric constant
organic semiconductors fall short to reduce strong Coulombic interaction of tightly bound
exciton and hence lead to a loss mechanism in OPVs due to charge-carrier recombination. To
circumvent this problem, we adopt a strategy to enhance the dielectric constant of organic
semiconductors by incorporating tetraethyleneglycol (TEG) side-chains. We report synthesis
of three new semiconducting copolymers by combining thiophene substituted
diketopyrrolopyrrole (TDPP) monomer with three other monomeric units with varying
electron donating strength: benzodithiophene (BBT-3TEG-TDPP), TDPP (TDPP-3TEG-TDPP)
and naphthalene diimide (PNDITEG-TDPP). BBT-3TEG-TDPP and PNDITEG-TDPP showed
highest dielectric constants (~ 5) at 1MHz frequency suggesting efficient contribution of
dipolar polarization from TEG side-chains. To understand the electronic contribution of the
polymer backbone and the polarity of TEG side-chains, and the resulting enhancement of the
dielectric constant, we further performed first-principles density functional theory
calculations. Single-component organic solar cells (OSC) fabricated utilizing these polymers
resulted in poor performance which is attributed to the absence of free charge generation.
Furthermore, transient absorption spectroscopy studies show low exciton diffusion length as
observed in donor-acceptor type conjugated polymers. Our results suggest that, the strategy
of enhancing dielectric constant with polar side-chains is not sufficient to reduce Coulombic
interaction between hole and electron in OSCs.
</p>
</div>
</div>
</div> | Aiswarya Abhisek Mohapatra; Yifan Dong; Puttaraju Boregowda; Ashutosh Mohanty; Aditya Sadhanala; Awadhesh Narayan; Chris McNeill; James R Durrant; Satish Patil; Xuechen Jiao; Priyakumari Chakkingal Parambil | Photovoltaics | CC BY NC 4.0 | CHEMRXIV | 2020-06-30 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/60c74d074c891945b9ad3744/original/rational-design-of-donor-acceptor-based-semiconducting-copolymers-with-high-dielectric-constant.pdf |
65ae2e529138d2316177c12e | 10.26434/chemrxiv-2024-r8h2d | Design of bright chemogenetic reporters based on the combined engineering of fluorogenic molecular rotors and of the HaloTag protein | The combination of fluorogenic probes (fluorogens) and self-labeling protein tags represent a promising tool for imaging biological processes with high specificity but it requires the adequation between the fluorogen and its target to ensure a good activation of its fluorescence. In this work, we report a strategy to develop molecular rotors that specifically target HaloTag with a strong enhancement of their fluorescence. The divergent design facilitates the diversification of the structures to tune the photophysical and cellular properties. Four bright fluorogens with emissions ranging from green to red were identified and applied in wash-free live cell imaging experiments with good contrast and selectivity. A HaloTag mutant adapted from previous literature reports was also tested and shown to further improve the brightness and reaction rate of the most promising fluorogen of the series both in vitro and in cells. This work opens new possibilities to develop bright chemogenetic reporters with diverse photophysical and biological properties by exploring a potentially large chemical space of simple dipolar fluorophores in combination with protein engineering. | Justine Coïs; Sylvestre Bachollet; Louis Sanchez; Vincent Vialou; Jean-Maurice Mallet; Blaise Dumat | Biological and Medicinal Chemistry; Chemical Biology | CC BY NC ND 4.0 | CHEMRXIV | 2024-01-24 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/65ae2e529138d2316177c12e/original/design-of-bright-chemogenetic-reporters-based-on-the-combined-engineering-of-fluorogenic-molecular-rotors-and-of-the-halo-tag-protein.pdf |
643ec31071383d0921eaa4e2 | 10.26434/chemrxiv-2023-203z9 | Plane waves versus correlation-consistent basis sets: A comparison of MP2 non-covalent interaction energies in the complete basis set limit | Second-order Møller Plesset perturbation theory (MP2) is the most expedient wavefunction-based method for considering electron correlation in quantum chemical calculations and as such provides a cost-effective framework to assess the effects of basis sets on correlation energies, for which the complete basis set (CBS) limit can commonly only be obtained via extrapolation techniques. Software packages providing MP2 energies are commonly based on atom-centered bases with innate issues related to possible basis set superposition errors (BSSE), especially in the case of weakly-bonded systems. Here, we present non-covalent interaction energies in the CBS limit, free of BSSE, for 20 dimer systems of the S22 dataset obtained via a highly-parallelized MP2 implementation in the plane-wave pseudopotential molecular dynamics package CPMD. The specificities related to plane waves for accurate and efficient calculations of gas-phase energies are discussed, and results compared to the localized (aug-)cc-pV[D,T,Q,5]Z correlation-consistent bases as well as their extrapolated CBS estimates. We find that the BSSE-corrected aug-cc-pV5Z basis can provide MP2 energies highly consistent with the CBS plane wave values with a minimum mean absolute deviation of ~0.05 kcal/mol without the application of any extrapolation scheme. In addition, we tested the performance of 13 different extrapolation schemes and found that the $X^{-3}$ expression applied to the (aug-)cc-pVXZ bases provides the smallest deviations against CBS plane wave values if the extrapolation sequence is composed of points D and T, while $(X + \frac{1}{2})^{-4}$ performs slightly better for TQ and Q5 extrapolations. Also, we propose $A (X-\frac{1}{2})^{-3} + B (X+\frac{1}{2})^{-4}$ as a reliable alternative to extrapolate total energies from the DTQ, TQ5 or DTQ5 data points. In spite of the general good agreement between the values obtained from the two types of basis set, it is noticed that differences between plane waves and (aug-)cc-pVXZ basis sets, extrapolated or not, tend to increase with the number of electrons, thus raising the question whether these discrepancies could indeed limit the attainable accuracy for localized bases in the limit of large systems. | Justin Villard; Martin Peter Bircher; Ursula Rothlisberger | Theoretical and Computational Chemistry; Computational Chemistry and Modeling; Theory - Computational | CC BY 4.0 | CHEMRXIV | 2023-04-20 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/643ec31071383d0921eaa4e2/original/plane-waves-versus-correlation-consistent-basis-sets-a-comparison-of-mp2-non-covalent-interaction-energies-in-the-complete-basis-set-limit.pdf |
61fb60c5c86ae203b6144823 | 10.26434/chemrxiv-2022-qs03q-v2 | Applicability Domain of Polyparameter Linear Free Energy Relationship Models Evaluated by Leverage and Prediction Interval Calculation | Polyparameter linear free energy relationships (PP-LFERs) are accurate and robust models employed to predict equilibrium partition coefficients (K) of organic chemicals. The accuracy of predictions by a PP-LFER depends on the composition of the respective calibration data set. Generally, extrapolation outside the model calibration domain is likely to be less accurate than interpolation. In this study, the applicability domain (AD) of PP-LFERs was systematically evaluated by calculating the leverage (h) and prediction interval (PI). Repeated simulations with experimental data showed that the root mean squared error of predictions increased with h. However, the analysis also showed that PP-LFERs calibrated with a large number (e.g., 100) of training data were highly robust against extrapolation error. For such well-calibrated PP-LFERs, the common definition of extrapolation (h > 3 hmean, where hmean is the mean h of all training compounds) may be excessively strict. Alternatively, the PI is proposed as a metric to define the AD of PP-LFERs, as it provides a concrete estimate of the error range that agrees well with the observed errors, even for extreme extrapolations. Additionally, published PP-LFERs were evaluated in terms of their AD using the new concept of AD probes, which indicated the varying predictive performance of PP-LFERs in existing literature for environmentally relevant compounds. | Satoshi Endo | Theoretical and Computational Chemistry; Physical Chemistry; Earth, Space, and Environmental Chemistry; Environmental Science; Chemoinformatics - Computational Chemistry; Physical and Chemical Properties | CC BY NC 4.0 | CHEMRXIV | 2022-02-03 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/61fb60c5c86ae203b6144823/original/applicability-domain-of-polyparameter-linear-free-energy-relationship-models-evaluated-by-leverage-and-prediction-interval-calculation.pdf |
612c8e3e65db1eaccca7fd95 | 10.26434/chemrxiv-2021-jmrvw-v3 | One-Pot Synthesis of High-Capacity Silicon-Lithium Anodes via On-Copper Growth of a Semi-Conducting, Porous Polymer | Silicon-based anodes with lithium ions as charge carriers have the highest predicted charge density of 3579 mA h g-1 (for Li15Si4). Contemporary electrodes do not achieve this theoretical value largely because conventional production paradigms rely on the mixing of weakly coordinated components. In this paper, a semi-conductive triazine-based graphdiyne polymer network is grown around silicon nanoparticles directly on the current collector, a copper sheet. The porous, semi-conducting organic framework (i) adheres to the current collector on which it grows via cooperative van der Waals interactions, (ii) acts effectively as conductor for electrical charges and binder of silicon nanoparticles via conjugated, covalent bonds, and (iii) enables selective transport of electrolyte and Li-ions through pores of defined size. The resulting anode shows extraordinarily high capacity at the theoretical limit of fully lithiated silicon. Finally, we combine our anodes in proof-of-concept battery assemblies using a conventional cathode, NCM811. | Michael J. Bojdys | Materials Chemistry | CC BY 4.0 | CHEMRXIV | 2021-08-30 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/612c8e3e65db1eaccca7fd95/original/one-pot-synthesis-of-high-capacity-silicon-lithium-anodes-via-on-copper-growth-of-a-semi-conducting-porous-polymer.pdf |
60c758b2469df4e850f456ff | 10.26434/chemrxiv.14579127.v1 | Limited-Resource Preparable Chitosan Magnetic Particles for Extracting Amplification-Ready Zeptomole-Range Nucleic Acid from Complex Biofluid | <b>Layman Summary: </b>Nucleic acid extraction is a key prerequisite for any nucleic acid amplification test (NAAT) or isothermal NAAT (iNAAT) based molecular diagnosis assays.<b> </b>Existing methods utilizes spin column system for nucleic acid extraction which are unsuitable for limited resource settings. Our work explores two methods for chitosan coated magnetic particle preparation that can be executed within 6 h from commonly available chemicals with nothing but a magnetic stirrer and water bath and doable by a minimally trained person. We will also investigated the compatibility of the extracted nucleic acid with downstream NAATs such as real time LAMP, colorimetric LAMP, and real time PCR. In the process, we established the analytical sensitivity of the overall method.<div><br /><div><b>Characterization methods</b>: SEM, XRD, EDX, FT-IR</div><div><br /></div><div><b>Bioanalytical methods:</b> Real time LAMP, Colorimetric LAMP, Real time PCR</div></div> | Sayantan Tripathy; Arunansu Talukdar; Goutam Pramanik; P. V. Rajesh; Souradyuti Ghosh | Magnetic Materials; Analytical Chemistry - General; Biochemical Analysis; Bioengineering and Biotechnology; Chemical Biology | CC BY NC ND 4.0 | CHEMRXIV | 2021-05-13 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/60c758b2469df4e850f456ff/original/limited-resource-preparable-chitosan-magnetic-particles-for-extracting-amplification-ready-zeptomole-range-nucleic-acid-from-complex-biofluid.pdf |
66713dd401103d79c577d386 | 10.26434/chemrxiv-2024-f11mm | Rethinking Oxygen Redox: Does Oxygen Dimerisation Occur without Oxidation in Li2NiO3? | In layered lithium transition metal oxide cathodes, high voltage operation is accompanied by the formation of oxygen dimers, which are widely used as an indicator of oxygen-redox activity. However, understanding the role that oxygen dimerisation plays in facilitating charge compensation is still needed. Here, Li2NiO3 (a 3d8L2-containing compound, where L is a ligand hole) is studied as a model system, where oxygen dimerisation is shown to occur without cathode oxidation. Electrochemical cycling results in a net reduction of the cathode structure, accompanied by structural transformations, despite spectroscopic features of oxygen dimers arising at the top of charge. Oxygen dimerisation is shown to coexist alongside a structurally transformed and electronically reduced cathode structure, thus raising questions about its origin with respect to delithiation. | Matthew J. W. Ogley; Ashok S. Menon; Beth J. Johnston; Gaurav Pandey; Innes McClelland; Xiaoqun Shi; Stefano Agrestini; Veronica Celorrio; Gabriel E. Pérez; Samuel G. Booth; Jordi Cabana; Serena A. Cussen; Louis F. J. Piper | Materials Science; Inorganic Chemistry; Energy; Energy Storage | CC BY NC ND 4.0 | CHEMRXIV | 2024-06-19 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/66713dd401103d79c577d386/original/rethinking-oxygen-redox-does-oxygen-dimerisation-occur-without-oxidation-in-li2ni-o3.pdf |
6427204ddb1a20696e505b9d | 10.26434/chemrxiv-2023-0kcb5 | Ligand-Enabled Ni(II)-Catalyzed Hydroxylarylation of Unactivated Alkenes With Molecular Oxygen | The use of molecular oxygen as the terminal oxidant in transition metal catalyzed oxidative process is an appealing and challenging task in organic synthetic chemistry. Here, we report a Ni-catalyzed hydroxylarylation of unactivated alkenes enabled by a β-diketone ligand with highly efficient and excellent regioselectivity employing molecular oxygen as the oxidant and hydroxyl source. This reaction features mild conditions, broad substrate scope and incredible heterocycle compatibility, providing a variety of β-hydroxylamides, γ-hydroxylamides, β-aminoalcohols, γ-aminoalcohols, and 1,3-diols in high yields. The synthetic value of this methodology was demonstrated by the efficient synthesis of two bioactive compounds, (±)-3’-methoxyl citreochilorol and tea catechin metabolites M4. | Dao-Ming Wang; Li-Qin She; Hao Yuan; Yichen Wu; Peng Wang | Organic Chemistry; Catalysis; Organic Synthesis and Reactions; Homogeneous Catalysis | CC BY NC 4.0 | CHEMRXIV | 2023-04-03 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/6427204ddb1a20696e505b9d/original/ligand-enabled-ni-ii-catalyzed-hydroxylarylation-of-unactivated-alkenes-with-molecular-oxygen.pdf |
60c73ed8bb8c1a7f423d99b1 | 10.26434/chemrxiv.7117895.v1 | Interfacial Heterogeneity is Essential to Water Extraction into Organic Solvents | Liquid/liquid extraction (LLE) is one of the most industrially relevant separations methods, successfully leveraging the variable solubility of solutes (or their complexes) between two immiscible solvents. Independently from the relative solubilities of those solutes and complexes which determine their distribution between phases, the kinetics of phase transfer is impacted by the molecular interactions and structure of those species at the interface. A simple example includes the formation and extraction of water-extractant adducts observed in the ternary water/organic/tri-n-butyl phosphate (TBP) system. Despite its implications for LLE, a detailed description of the structural and dynamic mechanisms by which such adducts are formed at the interface is not established. Describing that process requires connecting the evolving interfacial molecular organization in the presence of surfactants to dynamic surface fluctuations and interfacial heterogeneity. Herein, molecular dynamics simulation is combined with state of the art network theory analysis to reveal features of interfacial structure and their relationship to the extraction of water in the water/n-hexane/TBP system. Surfactant adsorption enhances interfacial roughness which in turn causes directly interfacial water to become less connected through hydrogen bonding to subjacent layers, particularly upon formation of the water bridged TBP dimer adduct. Further, heterogeneity within the interface itself is enhanced by surfactant adsorption, and serves as the basis for the formation of protrusions of water into the organic phase at the extremes of surface fluctuations. These features disproportionately incorporate the water bridged TBP dimer and are the primary means by which water is transferred to the organic phase. This work presents for the first time a holistic understanding of how interfacial heterogeneity and spatial fluctuations become amplified in the presence of surfactants, enabling water extraction into the organic phase. It further affords the opportunity to study how solution conditions can control interfacial behavior to create more efficient solvent extraction systems. | Michael Servis; Aurora Clark | Computational Chemistry and Modeling; Solution Chemistry | CC BY NC ND 4.0 | CHEMRXIV | 2018-09-24 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/60c73ed8bb8c1a7f423d99b1/original/interfacial-heterogeneity-is-essential-to-water-extraction-into-organic-solvents.pdf |
60c73d359abda23141f8b68a | 10.26434/chemrxiv.5496907.v1 | Constant pH Molecular Dynamics Reveals How Proton Release Drives the Conformational Transition of a Transmembrane Efflux Pump | AcrB is the inner-membrane transporter of E. coli AcrAB-TolC tripartite efflux complex, which plays a major role in the intrinsic resistance to clinically important antibiotics. AcrB pumps a wide range of toxic substrates by utilizing the proton gradient between periplasm and cytoplasm. Crystal structures of AcrB revealed three distinct conformational states of the transport cycle, substrate access, binding and extrusion, or loose (L), tight (T) and open (O) states. However, the specific residue(s) responsible for proton binding/release and the mechanism of proton-coupled conformational cycling remain controversial. Here we use the newly developed membrane hybrid-solvent continuous constant pH molecular dynamics technique to explore the protonation states and conformational dynamics of the transmembrane domain of AcrB. Simulations show that both Asp407 and Asp408 are deprotonated in the L/T states, while only Asp408 is protonated in the O state. Remarkably, release of a proton from Asp408 in the O state results in large conformational changes, such as the lateral and vertical movement of transmembrane helices as well as the salt-bridge formation between Asp408 and Lys940 and other sidechain rearrangements among essential residues.Consistent with the crystallographic differences between the O and L protomers, simulations offer dynamic details of how proton release drives the O-to-L transition in AcrB and address the controversy regarding the proton/drug stoichiometry. This work offers a significant step towards characterizing the complete cycle of proton-coupled drug transport in AcrB and further validates the membrane hybrid-solvent CpHMD technique for studies of proton-coupled transmembrane proteins which are currently poorly understood.
<p><br /></p> | Jana Shen; Zhi Yue; Helen Zgurskaya; Wei Chen | Computational Chemistry and Modeling | CC BY NC ND 4.0 | CHEMRXIV | 2017-10-16 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/60c73d359abda23141f8b68a/original/constant-p-h-molecular-dynamics-reveals-how-proton-release-drives-the-conformational-transition-of-a-transmembrane-efflux-pump.pdf |
60c740210f50db59403958f6 | 10.26434/chemrxiv.7638035.v1 | Methane/Carbon Dioxide Partitioning in Clay Nano- and Meso-Pores: Molecular Dynamics Modeling with Constant Reservoir Composition | <div>The interactions among fluid species such as H2O, CO2, and CH4 confined in nano- and meso-pores in shales and other rocks is of central concern to understanding the chemical behavior and transport properties of these species in the earth’s subsurface and is of special concern to geological C-sequestration and enhanced production of oil and natural gas. The behavior of CO2, and CH4 are less well understood than that of H2O. This paper presents the</div><div>results of a computational modeling study of the partitioning of CO2 and CH4 between bulk fluid and nano- and meso-pores bounded by the common clay mineral montmorillonite. The calculations were done at 323 K and a total fluid pressure of 124 bars using a novel approach (constant reservoir composition molecular dynamics, CRC-MD) that uses bias forces to maintain a constant composition in the fluid external to the pore. This purely MD approach overcomes the difficulties in making stochastic particle insertion-deletion moves in dense fluids encountered in grand canonical Monte Carlo and related hybrid approaches. The results show that both the basal siloxane surfaces and protonated broken edge surfaces of montmorillonite both prefer CO2 relative to CH4 suggesting that methods of enhanced oil and gas production using CO2 will readily displace CH4 from such pores. This preference for CO2 is due to its preferred interaction with the surfaces and extends to approximately 20 Å from them.</div> | A. Ozgur Yazaydin; Narasimhan Loganathan; Geoffrey Bowers; Andrey Kalinichev; Brice Firmin Ngouana Wakou; R. Jim Kirkpatrick | Computational Chemistry and Modeling; Interfaces; Physical and Chemical Processes | CC BY NC ND 4.0 | CHEMRXIV | 2019-01-29 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/60c740210f50db59403958f6/original/methane-carbon-dioxide-partitioning-in-clay-nano-and-meso-pores-molecular-dynamics-modeling-with-constant-reservoir-composition.pdf |
651bced9a69febde9e23b756 | 10.26434/chemrxiv-2023-9rg1d | The Missing Link for Electrochemical CO2 Reduction: Classification of CO vs. HCOOH Selectivity via PCA, Reaction Pathways and Coverage Analysis | For the electrochemical CO2 reduction reaction, different metal catalysts produce different products preferentially. However, the differences between the metals' reaction pathways that lead to these different products is still not fully understood. In this work, we analyze CO vs. HCOOH formation from CO2 using statistical analysis and DFT calculations. This is carried out by considering multiple descriptors, along with the competing reaction pathways, reaction barriers, and high coverage of mixed adsorbates on the surface. This method is capable of explaining the discrepancy between simulations and experiments regarding Ag and Au selectivity, and of properly classifying elements according to their product distribution. We find that, when considering water-assisted protonation for the disproportionation to CO, Ag and Au have a lower barrier for CO production in agreement with experimental results. We also find that, when considering high coverage of mixed adsorbates on the Ag/Au surface, the most stable adsorbate configuration contains adsorbates capable of forming CO preferentially. These findings help to bridge the gap between simulations and experiments and provide a missing link for our understanding of the CO2 reduction reaction. | Oliver Christensen; Alexander Bagger; Jan Rossmeisl | Materials Science; Catalysis; Catalysts; Electrocatalysis; Heterogeneous Catalysis; Materials Chemistry | CC BY 4.0 | CHEMRXIV | 2023-10-04 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/651bced9a69febde9e23b756/original/the-missing-link-for-electrochemical-co2-reduction-classification-of-co-vs-hcooh-selectivity-via-pca-reaction-pathways-and-coverage-analysis.pdf |
653904c2c573f893f10aec5c | 10.26434/chemrxiv-2023-w2db0-v2 | Paramagnetic NMR Shifts for Triplet Systems and Beyond with Modern Relativistic Density Functional Methods | An efficient framework for the calculation of paramagnetic NMR (pNMR) shifts within exact two-component (X2C) theory and (current-dependent) density functional theory (DFT) up to the class of local hybrid functionals is presented. Generally, pNMR shifts for systems with more than one unpaired electron depend on the orbital shielding contribution and a temperature-dependent term. The latter includes the zero-field splitting, the hyperfine coupling, and the g- tensor. For consistency, we calculate these three tensors at the same level of theory, i.e. using scalar-relativistic X2C augmented with spin–orbit perturbation theory. Results for pNMR chemical shifts of transition-metal complexes reveal that this X2C-DFT framework can yield good results for both the shifts and the individual tensor contributions of metallocenes and related systems, especially if the hyperfine coupling (HFC) constant is large. For small HFC constants, the relative error is often large and sometimes the sign may be off. 4d and 5d complexes with more complicated structures demonstrate the limitations of a fully DFT-based approach. Additionally, a Co-based complex with very large zero-field splitting and pronounced multireference character is not well described. Here, a hybrid DFT-multireference framework is necessary for accurate results. Our results show that X2C is sufficient to describe relativistic effects and computationally cheaper than a fully relativistic approach. Thus, it allows to use large basis sets for converged hyperfine couplings. Overall, current-dependent meta-generalized gradient approximations (meta-GGAs) and local hybrid functionals show some potential, however, the currently available functionals leave a lot to be desired. | Yannick J. Franzke; Florian Bruder; Sebastian Gillhuber; Christof Holzer; Florian Weigend | Theoretical and Computational Chemistry | CC BY NC ND 4.0 | CHEMRXIV | 2023-10-26 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/653904c2c573f893f10aec5c/original/paramagnetic-nmr-shifts-for-triplet-systems-and-beyond-with-modern-relativistic-density-functional-methods.pdf |
65b177d3e9ebbb4db9e6a4e7 | 10.26434/chemrxiv-2024-6t3wz | NaCl, MgCl2, and AlCl3 Surface Coverages on Fused Silica and Adsorption Free Energies at pH 4 From Nonlinear Optics | We employ amplitude- and phase-resolved SHG experiments to probe interactions of fused silica:aqueous interfaces with Al3+, Mg2+, and Na+ cations at pH 4 and as a function of metal cation concentration. We quantify the second-order nonlinear susceptibility and the total potential in the presence and absence of 10 mM screening electrolyte to understand the influence of charge screening on cation adsorption. Strong cation:surface interactions are observed in the absence of screen electrolyte. The total potential is then employed to estimate the total number of absorbed cations. The contributions to the total potential from the bound and mobile charge were separated using Gouy-Chapman-Stern model estimates. All three cations bind fully reversibly, indicating physisorption as the mode of interaction. Of the isotherm models tested, the Kd adsorption model fits the data with binding constants of 3 to 30 mol-1 and ~300 mol-1 for the low (<0.1 mM) and high (0.1 -3 mM) concentration regimes, corresponding to adsorption free energies of -13 to -18 and -24 kJ mol-1 at room temperature, respectively. The maximum surface coverages are around 1013 cations cm-2, matching the number of deprotonated silanol groups on silica at pH 4. Clear signs of decoupled Stern and diffuse layer nonlinear optical responses are observed and found to be cation specific. | Alyssa Olson; Amani Alghamdi; Franz Geiger | Physical Chemistry; Interfaces | CC BY 4.0 | CHEMRXIV | 2024-01-25 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/65b177d3e9ebbb4db9e6a4e7/original/na-cl-mg-cl2-and-al-cl3-surface-coverages-on-fused-silica-and-adsorption-free-energies-at-p-h-4-from-nonlinear-optics.pdf |
672cb71e5a82cea2fa60ad29 | 10.26434/chemrxiv-2024-ld07b-v3 | Orbital Exchange Calculations: An Alternative View of the Chemical Bond | Contemporary quantum chemistry methods assume that the two orbitals of the bonding pair are unambiguously identifiable. This work does not make that assumption. The purpose of this paper is to explore a model of the chemical bond which does not assume that the orbitals of the bonding pair can be unambiguously identified with either of the bonding atoms when their orbitals overlap to bond. To provide maximum flexibility in the definition of the bonding orbitals, the orbitals have been represented as spatial arrays and the calculations performed numerically. This model of the chemical bond assumes that the identifiability of the bonding orbitals is a function of 1-(overlap/(1+overlap)) where the overlap of the two bonding orbitals is calculated in the usual manner. The kinetic energy of the bonding electron pair and the energy required to meet the orthogonality requirements, mandated by the Pauli principle, are a function of overlap/(1+overlap). The model assumes that the bonding orbitals are straight-forward atomic orbitals or hybrids of these atomic orbitals. The results obtained by applying this simple approach to eleven di-atomics and seven common poly-atomics are quite good. The calculated bond lengths are generally within 0.005Å of the measured values and bond energies to within a few percent. Except for molecules with polarized symmetrical 1s or 2s sigma bonding orbitals, bond lengths are determined, independent of bond energy, at that point where overlap/(1+overlap) equals 0.5. | Paul Merrithew | Theoretical and Computational Chemistry; Computational Chemistry and Modeling | CC BY NC ND 4.0 | CHEMRXIV | 2024-11-08 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/672cb71e5a82cea2fa60ad29/original/orbital-exchange-calculations-an-alternative-view-of-the-chemical-bond.pdf |
651b985a006594091253fd2e | 10.26434/chemrxiv-2023-54bss | Target-Specific Novel Molecules with their Recipe: Incorporating Synthesizability in the Design Process | Application of Artificial intelligence (AI) in drug discovery has led to several success stories in recent times. While traditional methods mostly relied upon screening large chemical libraries for early-stage drug-design, the AI-based approaches can help identify novel target-specific molecules by sampling from a much larger chemical space. Although this has increased the possibility of finding diverse and novel molecules from previously unexplored chemical space, this has also posed a great challenge for medicinal chemists to synthesize at least some of the AI-designed novel molecules for experimental validation. To address this challenge, in this work, we propose a novel forward synthesis-based generative AI method, which is used to explore the synthesizable chemical space. The method uses a structure-based drug design framework, where the target protein structure and a target-specific seed fragment from co-crystal structures can be the initial inputs. A random fragment from a purchasable fragment library can also be the input if a target-specific fragment is unavailable. Then a template-based forward synthesis route prediction and molecule generation is performed in parallel using the Monte Carlo Tree Search (MCTS) method where, the subsequent fragments for molecule growth can again be obtained from a purchasable fragment library. To the best of our knowledge, this is the first model to utilize MCTS for forward synthesis route prediction. The rewards for each iteration of MCTS are computed using a drug-target affinity (DTA) model based on the docking pose of the generated reaction intermediates at the binding site of the target protein of interest. With the help of the proposed method, it is now possible to overcome one of the major obstacles posed to the AI-based drug design approaches through the ability of the method to design novel target-specific synthesizable molecules. | Sowmya Ramaswamy Krishnan; Navneet Bung; Rajgopal Srinivasan; Arijit Roy | Biological and Medicinal Chemistry; Bioinformatics and Computational Biology; Drug Discovery and Drug Delivery Systems | CC BY NC 4.0 | CHEMRXIV | 2023-10-04 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/651b985a006594091253fd2e/original/target-specific-novel-molecules-with-their-recipe-incorporating-synthesizability-in-the-design-process.pdf |
60c7426a0f50dbc5a5395cd3 | 10.26434/chemrxiv.8275325.v1 | Restriction of Access to Dark State: A New Mechanistic Model for Heteroatom-Containing AIE Systems | Aggregation-induced emission (AIE) is an unusual photophysical phenomenon and provides an effective and advantageous strategy for the design of highly emissive materials in versatile applications such as sensing, imaging, and theragnosis. "Restriction of intramolecular motion" is the well-recognized working mechanism of AIE and have guided the molecular design of most AIE materials. However, it sometimes fails to be workable to some heteroatom-containing systems. Herein, in this work, we take more than one excited state into account and specify a mechanism –"restriction of access to dark state (RADS)" – to explain the AIE effect of heteroatom-containing molecules. An anthracene-based zinc ion probe named APA is chosen as the model compound, whose weak fluorescence in solution is ascribed to the easy access from the bright (π,π*) state to the closelying dark (n,π*) state caused by the strong vibronic coupling of the two excited states. By either metal complexation or aggregation, the dark state is less accessible due to the restriction of the molecular motion leading to the dark state and elevation of the dark state energy, thus the emission of the bright state is restored. RADS is found to be powerful in elucidating the photophysics of AIE materials with excited states which favor non-radiative decay, including overlap-forbidden states such as (n,π*) and CT states, spin-forbidden triplet states, which commonly exist in heteroatom-containing molecules. | Yujie Tu; Junkai Liu; Haoke Zhang; Qian Peng; Jacky W. Y. Lam; Ben Zhong Tang | Optical Materials; Theory - Computational; Photochemistry (Physical Chem.); Physical and Chemical Processes; Physical and Chemical Properties | CC BY NC ND 4.0 | CHEMRXIV | 2019-06-17 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/60c7426a0f50dbc5a5395cd3/original/restriction-of-access-to-dark-state-a-new-mechanistic-model-for-heteroatom-containing-aie-systems.pdf |
641cbbb491074bccd02dd96f | 10.26434/chemrxiv-2023-374qx | The effect of local chain stiffness on the mechanism of crystal nucleation in an oligomer melt | While the process by which a polymer crystal nucleates from the melt has been extensively studied via molecular simulation, differences in polymer models and simulated crystallization conditions have led to contradictory results. We make steps to resolve this controversy by computing low-temperature phase diagrams of oligomer melts using Wang Landau Monte Carlo simulations. Two qualitatively different crystallization mechanisms are possible depending on the local bending stiffness potential. Polymers with a discrete bending potential crystallize via a single-step mechanism, whereas polymers with a continuous bending potential can crystallize via a two-step mechanism that includes an intermediate nematic phase. Other model differences can be quantitatively accounted for using an effective volume fraction and a temperature scaled by the bending stiffness. These results suggest that at least two universality classes of nucleation exist for melts and that local chain stiffness is a key determining factor in the mechanism of nucleation. | Pierre Kawak; Christopher Akiki; Douglas Tree | Theoretical and Computational Chemistry; Polymer Science; Theory - Computational | CC BY NC ND 4.0 | CHEMRXIV | 2023-03-24 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/641cbbb491074bccd02dd96f/original/the-effect-of-local-chain-stiffness-on-the-mechanism-of-crystal-nucleation-in-an-oligomer-melt.pdf |
67077d1251558a15efabf974 | 10.26434/chemrxiv-2024-089n1-v2 | Core Flipping in Lead Optimization: Rank Ordering using Multisite λ Dynamics | In structure-based drug discovery, reliable structural models of ligands bound to their target receptor are critical for establishing the structure activity relationship of congeneric series. In such a series, substitutions on a common scaffold core might lead to different binding modes, ranging from slight changes of orientations to flipping or inversion of the core structure. Moreover, molecular docking might lead to alternative orientations within the top ranked poses without being able to discriminate which is the most likely. To determine the relative binding affinities between two alternative ligand poses, we propose a methodology based on relative binding free energy calculations using the multisite λ dynamics method. We use a dual-topology approach with distance restraining schemes. We introduced a novel strategy using one-step perturbation to calculate the contributions of the applied restraints. While using FEP/MBAR instead for that purpose led to smaller uncertainties it suffered from convergence issues. We test the validity and predictive power of our approach using two pharmaceutically relevant targets and eight compounds from experimentally characterized congeneric series. For each target, our approach correctly ranks the known X-ray poses to be more favorable than alternative flipped poses. The proposed methodology can be easily extended to rank more than two poses in a single simulation and should also be applicable for the prediction of conformational binding cliffs, ranking fragments, core hopping cases and evaluating different scaffold binding to a common target. | Parveen Gartan; Charles L. Brooks III; Nathalie Reuter | Theoretical and Computational Chemistry | CC BY NC 4.0 | CHEMRXIV | 2024-10-10 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/67077d1251558a15efabf974/original/core-flipping-in-lead-optimization-rank-ordering-using-multisite-dynamics.pdf |
64ac43c29ea64cc167c91686 | 10.26434/chemrxiv-2023-rpn28 | Preparing chaperone—client protein complexes for biophysical and structural studies | Many proteins are prone to misfolding or unfolding and aggregation in the aqueous environment of the cell, either due to their complex ternary structure, cellular localization, molecular crowding, cellular stress, or their intrinsic hydrophobic nature. Molecular chaperones are involved in biogenesis of such proteins, and in ensuring their intactness throughout their life cycle. While there are many different types of chaperones with various cellular roles, essentially all of them are characterized by a basic “holdase” function, i.e. the ability to bind to proteins that are generally in some non-native conformation – often these are called “client” proteins. Understanding how these complexes form, what (residual) structure the client proteins have when bound, and how the client protein may eventually be released again from the chaperone is essential for resolving questions in biogenesis of cells and organelles. The preparation of chaperone complexes for in vitro studies is essential for characterising their function at the structural level. However, preparing these complexes is often a significant challenge in itself.
Here, we propose a systematic view of the factors that can counteract chaperone--client complex formation, and identify possible routes for generating such complexes. We review the various methods that have been used in previous studies. This review will be of interest for anyone trying to obtain chaperone complexes for structural or biochemical studies. | Iva Sučec; Paul Schanda | Biological and Medicinal Chemistry | CC BY NC ND 4.0 | CHEMRXIV | 2023-07-11 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/64ac43c29ea64cc167c91686/original/preparing-chaperone-client-protein-complexes-for-biophysical-and-structural-studies.pdf |
60c7437f469df42225f431de | 10.26434/chemrxiv.8061845.v2 | Quantum Chemical Methods for Modeling Covalent Modification of Biological Thiols | Targeted covalent inhibitor drugs require computational methods that go beyond simple molecular-mechanical force fields in order to model the chemical reactions that occur when they bind to their targets. Here, several semi-empirical and density-functional theory (DFT) methods are assessed for their ability to describe the potential energy surface and reaction energies of the covalent modification of a thiol by an electrophile. Functionals such as PBE and B3LYP fail to predict a stable enolate intermediate. This is largely due to delocalization error, which spuriously stabilizes the pre-reaction complex, in which excess electron density is transferred from the thiolate to the electrophile. Functionals with a high-exact exchange component, range-separated DFT functionals, and variationally-optimized exact exchange (i.e., the LC-B05minV functional) correct this issue to various degrees. The large gradient behaviour of the exchange enhancement factor is also found to significantly affect the results, leading to the improved performance of PBE0. While ωB97X-D and M06-2X were easonably accurate, no method provided quantitative accuracy for all three electrophiles, making this a very strenuous test of functional performance. Additionally, one drawback of M06-2X was that MD simulations using this functional were only stable if a fine integration grid was used. The low-cost semi-empirical methods, PM3, AM1, and PM7, provide a qualitatively correct description of the reaction mechanism, although the energetics are not quantitatively reliable. As a proof of concept, the potential of mean force for the addition of methylthiolate to MVK was calculated using QM/MM MD in an explicit polarizable aqueous solvent.<br /> | Ernest Awoonor-Williams; William Isley; Stephen Dale; Erin Johnson; Haibo Yu; Axel Becke; Benoît Roux; Christopher Rowley | Organic Compounds and Functional Groups; Bioinformatics and Computational Biology; Computational Chemistry and Modeling; Theory - Computational | CC BY NC ND 4.0 | CHEMRXIV | 2019-07-25 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/60c7437f469df42225f431de/original/quantum-chemical-methods-for-modeling-covalent-modification-of-biological-thiols.pdf |
62c82d0b14201f7a5a2b9f29 | 10.26434/chemrxiv-2022-39cff-v3 | Implementing an anonymized and scaffolded search at a primarily undergraduate institution | In 2021, the JMU Department of Chemistry and Biochemistry conducted a search for tenure track and renewable term appointment faculty. The search was anonymized and scaffolded to attract a diverse and highly qualified candidate pool and minimize bias during the hiring process. The department attracted a broad pool through national and targeted advertising. Candidates submitted a cover letter and curriculum vita which were redacted and reviewed using a rubric. Candidates who addressed the criteria in the job advertisement were invited to submit anonymized teaching and diversity statements (all candidates) and research statements (tenure track candidates) which were also reviewed using a rubric. Candidates who scored highly were invited to participate in a masked phone interview, and the top applicants were brought to campus for on site interviews. This process produced a candidate pool that became more diverse as the search continued. In this paper we describe the philosophy of the search process, describe how it was implemented, and provide recommendations for programs that wish to employ a similar process. | Barbara Reisner; Donna Amenta; Daniel Blumling; Jill Hagmaier; Christine Hughey; Qingsheng Liu; Isaiah Sumner; Linette Watkins | Chemical Education; Chemical Education - General | CC BY NC ND 4.0 | CHEMRXIV | 2022-07-11 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/62c82d0b14201f7a5a2b9f29/original/implementing-an-anonymized-and-scaffolded-search-at-a-primarily-undergraduate-institution.pdf |
6508432db6ab98a41ca9ca9e | 10.26434/chemrxiv-2023-1jssg | Direct deposition of complex polycrystalline colloidal monolayers on solid substrates from the evaporation of hanging drops | Microfabrication strategies designed to produce ordered arrangements of colloidal particles on solid supports are of great interest in materials science and technology due to their wide range of applications, from plasmonic and biomimetic surfaces to tags for anti-counterfeiting and goods identification. Existing methods allow excellent control over particle organization yet share a degree of complexity hampering their facile implementation. Here we present a simple methodology for creating ordered particle arrays on solid substrates only requiring the deposition on the target substrate of a colloidal suspension drop and flipping it upside-down for particle sedimentation, self-organization at air/water interface and evaporation-driven deposition. Particle adsorption at the air/water interface, here enabled by the addition of small amount of cationic surfactants, is critical to ensure two-dimensional confinement of repulsive particles and their self-assembly into extended ordered arrays prior to complete solvent evaporation and particle transfer to the substrate. We demonstrate the versatility of the method by the creation of arrays of various kinds of particles (silica, polystyrene) with diameters in the range 300 nm – 5 µm on different target substrates (polystyrene, polydimethylsiloxane, glass) as well as the generation of a variety of patterns. The size and morphology of the deposit, from single-crystals to multi-crystalline patches, can be controlled by the curvature of the drop and the total number of particles, while more complex colloidal structures, like colloidal crystal “alloys” and “irises” can be achieved by successive depositions, co-crystallization or double flipping. | Jacopo Vialetto; Théophile Gaichies; Sergii Rudiuk; Mathieu Morel; Damien Baigl | Physical Chemistry; Materials Science; Nanoscience; Nanostructured Materials - Materials; Interfaces; Self-Assembly | CC BY 4.0 | CHEMRXIV | 2023-09-19 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/6508432db6ab98a41ca9ca9e/original/direct-deposition-of-complex-polycrystalline-colloidal-monolayers-on-solid-substrates-from-the-evaporation-of-hanging-drops.pdf |
60c74608f96a008bf5286cb6 | 10.26434/chemrxiv.9912860.v2 | Benchmark of Simplified Time-Dependent Density Functional Theory for UV-Vis Spectral Properties of Porphyrinoids | <p>We thoroughly benchmark
time-dependent density- functional theory for the predictive calculation of
UV/Vis spectra of porphyrin derivatives. With the aim to provide an approach
that is computationally feasible for large-scale applications such as
biological systems or molecular framework materials, albeit performing with
high accuracy for the Q-bands, we compare the results given by various computational
protocols, including basis sets, density-functionals (including gradient
corrected local functionals, hybrids, double hybrids and range-separated
functionals), and various variants of time-dependent density-functional theory,
including the simplified Tamm-Dancoff approximation. An excellent choice for
these calculations is the range-separated functional CAM-B3LYP in combination
with the simplified Tamm-Dancoff approximation and a basis set of double-ζ
quality def2-SVP (mean absolute error [MAE] of ~0.05 eV). This is not surpassed
by more expensive approaches, not even by double hybrid functionals, and solely
systematic excitation energy scaling slightly improves the results (MAE ~0.04
eV). </p> | Kamal Batra; Stefan Zahn; Thomas Heine | Theory - Computational | CC BY 4.0 | CHEMRXIV | 2019-11-13 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/60c74608f96a008bf5286cb6/original/benchmark-of-simplified-time-dependent-density-functional-theory-for-uv-vis-spectral-properties-of-porphyrinoids.pdf |
666d872701103d79c547c3c1 | 10.26434/chemrxiv-2024-2s98x | Autonomous Size-Targeting for Block Copolymer Nanoparticles | Using the combination of flow synthesis with online dynamic light scattering (DLS) analysis for particle size characterization and fully autonomous computer control allows for reproducible and targetable synthesis of nanoparticles from block copolymer (BCP) solutions by rapid mixing with water in a defined micromixer environment. Using Bayesian optimization (BO), nanoparticle sizes become programmable and preselectable, and awide range of sizes can be obtained per used BCP. Specifically, we show for a series of polystyrene-b-poly(N,N- dimethyl acrylamide) and polystyrene-b-poly(poly(ethylene glycol) methyl ether acrylate) BCPs, how particles spanning from 130 to 280 nm can be systematically targeted, with sizes between 100 and 1000 nm being at least in principle also achievable. Further, Pareto fronts for the individual synthesis parameters overall flow rate, water volume fraction and polymer concentration are obtained from the established routines and presented. This BO approach highlights the efficacy of autonomous flow platforms in achieving precise control over polymer self-assembly processes, offering an optimal production window for the development and optimization of polymeric nanostructures in diverse fields such as drug delivery and materials science. | Oliver Weismantel; Lakshani Weerarathna; Tanja Junkers | Polymer Science | CC BY 4.0 | CHEMRXIV | 2024-06-18 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/666d872701103d79c547c3c1/original/autonomous-size-targeting-for-block-copolymer-nanoparticles.pdf |
60c75312469df47cd5f44ca9 | 10.26434/chemrxiv.13383275.v1 | Data Augmentation and Transfer Learning Strategies for Reaction Prediction in Low Chemical Data Regimes | <p><b>Abstract:</b> Effective and rapid deep learning method to predict chemical reactions contributes to the research and development of organic chemistry and drug discovery. Despite the outstanding capability of deep learning in retrosynthesis and forward synthesis, predictions based on small chemical datasets generally result in low accuracy due to an insufficiency of reaction examples. Here, we introduce a new state art of method, which integrates transfer learning with transformer model to predict the outcomes of the Baeyer-Villiger reaction which is a representative small dataset reaction. The results demonstrate that introducing transfer learning strategy markedly improves the top-1 accuracy of the transformer-transfer learning model (81.8%) over that of the transformer-baseline model (58.4%). Moreover, we further introduce data augmentation to the input reaction SMILES, which allows for better performance and improves the accuracy of the transformer-transfer learning model (86.7%). In summary, both transfer learning and data augmentation methods significantly improve the predictive performance of transformer model, which are powerful methods used in chemistry field to eliminate the restriction of limited training data.</p> | Yun Zhang; Ling Wang; Xinqiao Wang; Chengyun Zhang; Jiamin Ge; Jing Tang; An Su; Hongliang Duan | Computational Chemistry and Modeling; Chemoinformatics - Computational Chemistry | CC BY NC ND 4.0 | CHEMRXIV | 2020-12-17 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/60c75312469df47cd5f44ca9/original/data-augmentation-and-transfer-learning-strategies-for-reaction-prediction-in-low-chemical-data-regimes.pdf |
60c75420567dfe7195ec6022 | 10.26434/chemrxiv.13615385.v1 | Amyloid like Aggregates Formed by the Self-Assembly of Proline and Hydroxyproline | <p>Single amino acid based self-assembled structures have gained a lot of
interest recently owing to their pathological significance in metabolite
disorders. There is plethora of significant research work which illustrate
amyloid like characteristics of assemblies formed by aggregation of single
amino acids like Phenylalanine, Tyrosine, Tryptophan, Cysteine and Methionine
and its implications in pathophysiology of single amino acid metabolic
disorders like phenylketonuria, tyrosinemia, hypertryptophanemia, cystinuria
and hypermethioninemia respectively. Hence, studying aggregation behaviour of
single amino acids is very crucial to assess the underlying molecular mechanism
behind metabolic disorders. In this manuscript we report for the very first
time the aggregation properties of non-aromatic single amino acids
Hydroxy-proline and Proline. The morphologies of these were studied extensively
by Optical microscopy (OM), ThT binding fluorescence microscopy, Scanning
Electron Microscopy (SEM) and Atomic force microscopy (AFM). It can be
assessed that these amino acids form globular structures at lower concentrations
and gradually changes to tape like structures on increasing the concentration
as assessed by AFM. ThT and CR binding assay reveal the aggregates do have
amyloid like characteristics. Further MTT assays on SHSY5Y neural cell lines
reveal cytotoxicity and the aggregates caused significant cell death in dose
dependent manner. These results have important implications in understanding
the pathophysiology of single amino acid disorders like Hyperprolinemia
and Hydroxyprolinemia in association with amyloid diseases. The symptoms of
these diseases are also accompanied by extensive neurological problems like
intellectual disability, seizures and psychiatric problems which further evince
amyloid like etiology for these rare in-born errors of metabolism.</p> | Bharti Koshti; Ramesh, Singh; Vivekshinh Kshtriya; Shanka Walia; Dhiraj Bhatia; khashti Ballabh Joshi; Nidhi Gour | Biochemistry; Chemical Biology; Drug Discovery and Drug Delivery Systems | CC BY NC ND 4.0 | CHEMRXIV | 2021-01-21 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/60c75420567dfe7195ec6022/original/amyloid-like-aggregates-formed-by-the-self-assembly-of-proline-and-hydroxyproline.pdf |
677eba45fa469535b936286a | 10.26434/chemrxiv-2025-2f149 | JOYCE3.0: A General Protocol for the Specific Parameterization of Accurate Intramolecular Quantum Mechanically Derived Force-Fields | While the intrinsically multi-scale nature of most advanced materials necessitates the use of cost-effective computational models based on classical physics, a reliable description of the structure and dynamics of their components often requires a quantum-mechanical treatment. In this work, we present JOYCE3.0, a software package for the parameterization of accurate, quantum-mechanically derived force-fields (QMD-FFs). Since its original release, the code has been extensively automated and expanded, with all novel implementations thoroughly discussed. To illustrate its general applicability, QMD-FFs are parameterized for seven benchmark cases, encompassing molecules with diverse structure and properties. These range from exotic stiff scaffolds, flexible polymeric chains, and polyenes of biological interest to transition-metal complexes. On the one hand, JOYCE3.0 FFs consistently outperform available general purpose descriptions, achieving excellent agreement with higher-level theoretical methods or available experimental validation data. On the other hand, the remarkable accuracy found in the description of the molecular structures extends to electronic excited states, enabling the integration of the JOYCE3.0 QMD-FFs into multi-level protocols aimed at reliably predicting selected properties and spectral lineshapes in advanced optoelectronic materials. The high quality of the results — spanning molecular structures, condensed-phase properties, and spectroscopic features—combined with the enhanced interface with popular quantum-mechanical codes and molecular dynamics engines, as well as its applicability to chemically diverse species, strongly suggests that JOYCE3.0 could play a pivotal role in the rational design of functionalized materials and heterogeneous systems. | Samuele Giannini; Pablo M. Martinez; Abderrahmane Semmeq; J. Pablo Galvez; Anna Piras; Alessandro Landi; Daniele Padula; J.G. Vilhena; Javier Cerezo; Giacomo Prampolini | Theoretical and Computational Chemistry; Computational Chemistry and Modeling; Theory - Computational | CC BY 4.0 | CHEMRXIV | 2025-01-10 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/677eba45fa469535b936286a/original/joyce3-0-a-general-protocol-for-the-specific-parameterization-of-accurate-intramolecular-quantum-mechanically-derived-force-fields.pdf |
658e8b7966c13817294470ee | 10.26434/chemrxiv-2024-n4k20 | Some features of photoelectrophysical properties of new photosensitive composites based on naphthalimide-containing copolymer sensitized by organic dyes | Novel polymeric film composites based on naphthalimide-containing methacrylic copolymer doped with symmetrical cationic polymethine dyes with different polymethine chain length have been prepared. It was found that the obtained film composites exhibit photovoltaic properties in the absorption spectral region of the dyes. If the length of the polymethine chain is reduced the value of the photovoltaic response is increased as a result of decrease in the energy of the highest occupied orbital of the dye molecule. In the samples of the composite films with a free film surface the photovoltaic effect is determined by diffusion of the more mobile photogenerated positive charge carriers and by their recombination time. | Irina Savchenko; Sergey Studzinsky; Hanna Solodukha; Iryna Davidenko; Olena Mokrinska; Valeriy Pavlov; Nicolay Chuprina; Victor Kravchenko | Materials Science; Dyes and Chromophores | CC BY 4.0 | CHEMRXIV | 2024-01-02 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/658e8b7966c13817294470ee/original/some-features-of-photoelectrophysical-properties-of-new-photosensitive-composites-based-on-naphthalimide-containing-copolymer-sensitized-by-organic-dyes.pdf |
61e11940f2bef70ab3a11c3c | 10.26434/chemrxiv-2022-3tjvp | Topological reference systems | A topological reference system is a theory that allows the visualization of the effects of a ring structure on the energy stabilization of π-electron conjugated systems. In this study, the original paper was reconfigured to introduce the definition of the topological reference system and practical calculation method. | OHMAE TAKAYUKI OHMAE | Theoretical and Computational Chemistry; Organic Chemistry; Computational Chemistry and Modeling; Theory - Computational | CC BY NC ND 4.0 | CHEMRXIV | 2022-01-20 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/61e11940f2bef70ab3a11c3c/original/topological-reference-systems.pdf |
60c74f1c337d6c1f57e28095 | 10.26434/chemrxiv.12847913.v1 | Unusual Spectroscopic and Electric Field Sensitivity of a Chromophore with Short Hydrogen Bond: GFP and PYP as Model Systems | <p>
Short hydrogen bonds, with heavy-atom distances less than 2.7 Å,
are believed to exhibit proton delocalization
and their possible role in catalysis has been widely debated. While
spectroscopic and/or structural methods are usually employed to study
the degree of proton delocalization, ambiguities still arise and no
direct information on the corresponding potential energy
surface is obtained. Here we apply an external electric field to perturb
the short hydrogen bond(s)
within a collection of green fluorescent protein S65T/H148D variants
and photoactive yellow protein mutants, where
the chromophore participates in the short hydrogen bond(s) and serves as
an optical probe of the proton position. As the proton is charged, its
position may shift in response to the external electric field, and the
chromophore’s electronic absorption can thus
reflect the ease of proton transfer. The results suggest that
low-barrier hydrogen bonds are not present within these proteins even when proton affinities between donor and acceptor are closely matched. Exploiting
the chromophores as pre-calibrated electrostatic probes, the covalency of short hydrogen bonds
as a non-electrostatic component was also revealed. No clear evidence
was found for a possible
contribution of unusually large polarizabilities of short hydrogen bonds
due to proton delocalization; a theoretical framework for this
interesting phenomenon is developed.<br /></p> | Chi-Yun Lin; Steven Boxer | Biophysical Chemistry; Photochemistry (Physical Chem.); Physical and Chemical Properties; Quantum Mechanics; Spectroscopy (Physical Chem.); Structure; Crystallography | CC BY NC ND 4.0 | CHEMRXIV | 2020-08-24 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/60c74f1c337d6c1f57e28095/original/unusual-spectroscopic-and-electric-field-sensitivity-of-a-chromophore-with-short-hydrogen-bond-gfp-and-pyp-as-model-systems.pdf |
60c74aef567dfe1088ec4e6f | 10.26434/chemrxiv.12264077.v1 | Size Evolution and Composition of the Intermediate Phase During Nonclassical Protein Crystal Growth from Solution | <div>We propose here that the intermediate nucleation phase identified in a certain case</div><div>of protein crystal growth actually consists of two distinct parts; a low density and</div><div>higher density phase. A theory for crystal growth is utilized to study the formation</div><div>and growth of each phase. Within the framework of this theory the low density phase</div><div>is shown to obey a forth order kinetic law while the high density phase is zeroth order.</div><div>The combination of these two phases is shown to be a good match for X-ray diffraction </div><div>data which is indicative of its presence. The crystal growth rate is then given</div><div>in terms of the kinetic behavior of the intermediate nucleation phase. From this, the</div><div>crystal radius is estimated and shown to compare favorably with reported size data.</div><div>A method is proposed for determining the conditions that lead to protein crystals of</div><div>largest possible size.</div> | Douglas Barlow; Jan Gregus | Clusters; Solution Chemistry | CC BY NC ND 4.0 | CHEMRXIV | 2020-05-12 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/60c74aef567dfe1088ec4e6f/original/size-evolution-and-composition-of-the-intermediate-phase-during-nonclassical-protein-crystal-growth-from-solution.pdf |
619d6670f93ad37b30b19430 | 10.26434/chemrxiv-2021-gq1jb-v2 | Tropane and Related Alkaloid Skeletons via a Radical [3+3]-Annulation Process | A mild and simple protocol for the synthesis of 8-azabicyclo[3.2.1]octane and 9-azabicyclo[3.3.1]nonane derivatives is described. It provides these valuable bicyclic alkaloid skeletons in good yields and high levels of diastereoselectivity from simple and readily available starting materials using visible-light photoredox catalysis. This unprecedented annulation process takes advantage of the unique reactivity of ethyl 2-(acetoxymethyl)acrylate as a 1,3-bis radical acceptor and of cyclic N,N-dialkylanilines as radical 1,3-bis radical donors. The success of this process relies on efficient electron transfer processes and highly selective deprotonation of aminium radical cations leading to the key α-amino radical intermediates. | Eloïse Colson; Julie Andrez; Ali Dabbous; Frabrice Dénès; Vincent Maurel; Jean-Marie Mouesca; Philippe Renaud | Biological and Medicinal Chemistry; Organic Chemistry; Catalysis | CC BY 4.0 | CHEMRXIV | 2021-11-24 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/619d6670f93ad37b30b19430/original/tropane-and-related-alkaloid-skeletons-via-a-radical-3-3-annulation-process.pdf |
60c73d3bbdbb89110aa37c15 | 10.26434/chemrxiv.5513581.v1 | Mol2vec: Unsupervised Machine Learning Approach with Chemical Intuition | Inspired by natural language processing techniques we here introduce Mol2vec which is an unsupervised machine learning approach to learn vector representations of molecular substructures. Similarly, to the Word2vec models where vectors of closely related words are in close proximity in the vector space, Mol2vec learns vector representations of molecular substructures that are pointing in similar directions for chemically related substructures. Compounds can finally be encoded as vectors by summing up vectors of the individual substructures and, for instance, feed into supervised machine learning approaches to predict compound properties. The underlying substructure vector embeddings are obtained by training an unsupervised machine learning approach on a so-called corpus of compounds that consists of all available chemical matter. The resulting Mol2vec model is pre-trained once, yields dense vector representations and overcomes drawbacks of common compound feature representations such as sparseness and bit collisions. The prediction capabilities are demonstrated on several compound property and bioactivity data sets and compared with results obtained for Morgan fingerprints as reference compound representation. Mol2vec can be easily combined with ProtVec, which employs the same Word2vec concept on protein sequences, resulting in a proteochemometric approach that is alignment independent and can be thus also easily used for proteins with low sequence similarities. | Sabrina Jaeger; Simone Fulle; Samo Turk | Computational Chemistry and Modeling | CC BY NC ND 4.0 | CHEMRXIV | 2017-10-23 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/60c73d3bbdbb89110aa37c15/original/mol2vec-unsupervised-machine-learning-approach-with-chemical-intuition.pdf |
60c73e18469df44f80f4280f | 10.26434/chemrxiv.6635312.v1 | Palladium-Catalyzed Asymmetric Annulation Between Aryl Iodides and Racemic Epoxides Using a Chiral Norbornene Cocatalyst | Herein, we describe our initial development of an asymmetric Pd-catalyzed annulation between aryl iodides and racemic epoxides for synthesis of 2,3-dihydrobenzofurans using a chiral norbornene cocatalyst. A series of enantiopure ester-, amide- and imide-substituted norbornenes have been prepared with a reliable synthetic route. Promising enantioselectivity (42-45% ee) has been observed using the isopropyl ester-substituted norbornene (N1*) and the amide-substituted norbornene (N7*). | Guangbin Dong; Renhe Li | Organocatalysis; Catalysis; Ligands (Organomet.); Reaction (Organomet.) | CC BY NC ND 4.0 | CHEMRXIV | 1970-01-01 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/60c73e18469df44f80f4280f/original/palladium-catalyzed-asymmetric-annulation-between-aryl-iodides-and-racemic-epoxides-using-a-chiral-norbornene-cocatalyst.pdf |
6409da486642bf8c8f3a3fa1 | 10.26434/chemrxiv-2023-5cb8g | Transition Metal Isocorroles as Singlet Oxygen Sensitizers | Building on a highly efficient synthesis of pyrrole-appended isocorroles, we have worked out conditions for manganese, palladium, and platinum insertion into free-base 5/10-(2-pyrrolyl)-5,10,15-tris(4-methylphenyl)isocorrole, H2[5/10-(2-py)TpMePiC]. Platinum insertion proved exceedingly challenging but was finally accomplished with cis-Pt(PhCN)2Cl2. All the complexes proved weakly phosphorescent in the near-infrared under ambient conditions, with a maximum phosphorescence quantum yield of 0.1% observed for Pd[5-(2-py)TpMePiC]. The emission maximum proved was found to exhibit a strong metal ion dependence for the 5-regiosomeric complexes, but not for the 10-regioisomers. Despite the low phosphorescence quantum yields, all the complexes were found to sensitize singlet oxygen formation with moderate to good efficiency, with singlet oxygen quantum yields ranging over 21-52%. With significant absorption in the near-infrared and good singlet oxygen-sensitizing ability, metalloisocorroles deserve examination as photosensitizers in photodynamic therapy of cancer and other diseases. | Simon Larsen; Joseph Adewuyi; Gael Ung; Abhik Ghosh | Biological and Medicinal Chemistry; Materials Science; Inorganic Chemistry; Photosensitizers; Ligands (Inorg.); Transition Metal Complexes (Inorg.) | CC BY NC ND 4.0 | CHEMRXIV | 2023-03-10 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/6409da486642bf8c8f3a3fa1/original/transition-metal-isocorroles-as-singlet-oxygen-sensitizers.pdf |
667ab2085101a2ffa877671b | 10.26434/chemrxiv-2024-hkszt-v2 | Discovery of Crystallizable Organic Semiconductors with Machine Learning | Crystalline organic semiconductors are known to have improved charge carrier mobility and exciton diffusion length in comparison to their amorphous counterparts. Certain organic molecular thin films can be transitioned from initially prepared amorphous layers to large-scale crystalline films via abrupt thermal annealing. Ideally, these films crystallize as platelets with long-range-ordered domains on the scale of tens to hundreds of microns. However, other organic molecular thin films may instead crystallize as spherulites or resist crystallization entirely. Organic molecules that have the capability of transforming into a platelet morphology feature both high melting point (Tm) and crystallization driving force (ΔGc). In this work, we employed machine learning (ML) to identify candidate organic materials with the potential to crystallize into platelets by estimating the aforementioned thermal
properties. Six organic molecules identified by the ML algorithm were experimentally evaluated; three crystallized as platelets, one crystallized as a spherulite, and two resisted thin film crystallization. These results demonstrate a successful application of ML in the scope of predicting thermal properties of organic molecules and reinforce the principles of Tm and ΔGc as metrics that govern the crystallization of organic thin films. | Holly M. Johnson; Filipp Gusev; Jordan T. Dull; Yejoon Seo; Rodney D. Priestley; Olexandr Isayev; Barry P. Rand | Theoretical and Computational Chemistry; Physical Chemistry; Machine Learning; Chemoinformatics - Computational Chemistry; Materials Chemistry; Crystallography | CC BY NC 4.0 | CHEMRXIV | 2024-06-25 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/667ab2085101a2ffa877671b/original/discovery-of-crystallizable-organic-semiconductors-with-machine-learning.pdf |
60c7522eee301c584cc7ab6b | 10.26434/chemrxiv.13262771.v1 | Protein Acylation by Saturated Very Long Chain Fatty Acids and Endocytosis Are Involved in Necroptosis | <p>Necroptosis is a form of regulated cell death that is characterized by membrane
permeabilization. This permeabilization is responsible for the inflammatory properties of
necroptosis and is critical for disease states involving this process. We previously showed that
very long chain fatty acids (VLCFAs) are functionally involved in necroptosis, potentially through
protein fatty acylation. Here, we define the scope of protein acylation by saturated VLCFAs
during necroptosis. We show that mixed lineage kinase like protein (MLKL) and phosphoMLKL,
key proteins for membrane permeabilization, are exclusively acylated during necroptosis.
Reducing the levels of VLCFAs decreases their membrane recruitment, suggesting that
acylation by VLCFAs contributes to their membrane localization. Acylation of phosphoMLKL
occurs downstream of phosphorylation and oligomerization and appears to be, in part, mediated
by ZDHHC5 (a palmitoyl transferase). We also show that disruption of the clathrin-mediated
endocytosis increases cell viability during necroptosis, likely by removing phosphoMLKL from
the plasma membrane. <br /></p> | Apoorva Pradhan; Daniel Lu; Laura Parisi; Shichen Shen; Ilyas Berhane; Samuel L. Galster; Kiana Bynum; Viviana Monje-Galvan; Omer Gokcumen; Sherry Chemler; Jun Qu; Jason G. Kay; Ekin Atilla-Gokcumen | Biochemistry; Cell and Molecular Biology; Chemical Biology | CC BY NC ND 4.0 | CHEMRXIV | 2020-11-20 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/60c7522eee301c584cc7ab6b/original/protein-acylation-by-saturated-very-long-chain-fatty-acids-and-endocytosis-are-involved-in-necroptosis.pdf |
67c9d3d46dde43c908c6c0b8 | 10.26434/chemrxiv-2025-jm423 | Dynamics and structural responses to cis-trans isomerization in bacterial lipid bilayers | Bacterial and eukaryotic cells must respond to a changing environment, and have multiple adaptive mechanisms to respond to environmental stresses. Exogenous stresses such as temperature fluctuations and osmotic pressure are known to influence cell membrane fluidity and gene expression. To maintain membrane homeostasis, gram-negative bacteria show a short-term membrane composition response to temperature changes. Specifically, these bacteria isomerize unsaturated fatty acid tails in their bilayers, switching unsaturation sites from the more common cis isomer to the trans isomer. Cis-trans isomerization in unsaturated fatty acids increases cell membrane rigidity, decreasing fluidity of the lipid acyl tails. These changes maintain membrane homeostasis, but the effect size is difficult to quantify in vivo. In this work, we explore the impact of fatty acid cis-trans isomerization on the properties and dynamics in a membrane model based on Pseudomonas putida using molecular dynamics (MD) simulation. In our hypothetical model, we convert between all-cis and all-trans membranes, and report on the variation in membrane properties under these conditions. In addition to changes in membrane thickness and lipid diffusion, we find that the unsaturation site for a cis fatty acid has a higher probability to come to the membrane surface than the equivalent trans fatty acid. The reduced availability of unsaturation sites on the membrane surface may have downstream implications for their accessibility to enzymatic attack, potentially influencing the activity of cis-trans isomerase and other peripheral membrane proteins that act on lipid unsaturations. Since cis-trans isomerization can occur rapidly without new lipid biosynthesis, natural selection has adopted cis-trans isomerization as one of many responses to environmental stress. | Saad Raza; Majid Jafari; Troy Sievertsen; Josh Vermaas | Physical Chemistry; Biophysical Chemistry | CC BY 4.0 | CHEMRXIV | 2025-03-10 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/67c9d3d46dde43c908c6c0b8/original/dynamics-and-structural-responses-to-cis-trans-isomerization-in-bacterial-lipid-bilayers.pdf |
619ff720a9c8d59f4d5dfbc6 | 10.26434/chemrxiv-2021-nwd05 | High harmonic spectra computed using time-dependent Kohn-Sham theory with Gaussian orbitals and a complex absorbing potential | High harmonic spectra for H2 are simulated by solving the time-dependent Kohn-Sham equation in the presence of a strong laser field, using an atom-centered Gaussian representation of the orbitals and a complex absorbing potential to mitigate artifacts associated with the finite extent of the basis functions, such as spurious reflection of the outgoing electronic wave packet. Interference between the outgoing and reflected waves manifests
in the Fourier transform of the time-dependent dipole moment function and leads to peak broadening in the high harmonic spectrum as well as the appearance of spurious peaks at energies well above the cutoff energy
at which the harmonic progression is expected terminate.
We demonstrate that well-resolved spectra can be obtained through the use of an atom-centered absorbing potential. As compared to grid-based algorithms for solving the time-dependent Kohn-Sham equations, the present approach is more readily extendible to larger polyatomic molecules.
| Ying Zhu; John Herbert | Theoretical and Computational Chemistry; Physical Chemistry; Theory - Computational; Quantum Mechanics; Spectroscopy (Physical Chem.) | CC BY 4.0 | CHEMRXIV | 2021-11-26 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/619ff720a9c8d59f4d5dfbc6/original/high-harmonic-spectra-computed-using-time-dependent-kohn-sham-theory-with-gaussian-orbitals-and-a-complex-absorbing-potential.pdf |
616052292aca53bca55cc6b5 | 10.26434/chemrxiv-2021-nftrb | NIR-Responsive Lysosomotropic Phototrigger: ʽAIE + ESIPTʼ Active Naphthalene Based Single Component Photoresponsive Nanocarrier with Two-Photon Uncaging and Real-Time Monitoring Ability | In recent times, organelle-targeted drug delivery systems gained tremendous attention due to the site specific delivery of active drug molecules resulting in enhanced bioefficacy. In this context, the phototriggered drug delivery system (DDS) for releasing an active molecule is superior as it provides spatial and temporal control over the release. So far, near infrared (NIR) light responsive organelle targeted DDS has not yet been developed. Hence, we introduced a two-photon NIR-light responsive lysosome targeted ʽAIE + ESIPTʼ active single component DDS based on naphthalene chromophore. The Two-photon absorption cross-section of our DDS is 142 GM at 850 nm. The DDS was converted into pure organic nanoparticles for biological applications. Our nano-DDS is capable of selective targeting, AIE-luminogenic imaging, and drug release within the lysosome. In vitro studies using cancerous cell lines showed that our single component photoresponsive nanocarrier exhibited enhanced cytotoxicity and real-time monitoring ability of the drug release.
| Biswajit Roy; Rakesh Mengji; Samrat Roy; Bipul Pal; Avijit Jana; N. D. Pradeep Singh | Biological and Medicinal Chemistry; Organic Chemistry; Photochemistry (Org.) | CC BY NC ND 4.0 | CHEMRXIV | 2021-10-11 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/616052292aca53bca55cc6b5/original/nir-responsive-lysosomotropic-phototrigger-aie-esipt-active-naphthalene-based-single-component-photoresponsive-nanocarrier-with-two-photon-uncaging-and-real-time-monitoring-ability.pdf |
60c74b10337d6c17bee27a03 | 10.26434/chemrxiv.12280289.v1 | Optimization of a New Reactive Force Field for Silver - Based Materials | <div><div><div><p>A new reactive force field based on the ReaxFF formalism is effectively parametrized against an extended training set of quantum chemistry data (containing more than 120 different structures) to describe accurately silver- and silver-thiolate systems. The results obtained with this novel representation demonstrate that the novel ReaxFF paradigm is a powerful methodology to reproduce more appropriately average geometric and energetic properties of metal clusters and slabs when compared to the earlier ReaxFF parametrizations dealing with silver and gold. ReaxFF cannot describe adequately specific geometrical features such as the observed shorter distances between the under-coordinated atoms at the cluster edges. Geometric and energetic properties of thiolates adsorbed on a silver Ag20 pyramid are correctly represented by the new ReaxFF and compared with results for gold. The simulation of self-assembled monolayers of thiolates on a silver (111) surface does not indicate the formation of staples in contrast to the results for gold-thiolate systems.</p></div></div></div> | Clément Dulong; Bruno Madebène; Susanna Monti; Johannes Richardi | Computational Chemistry and Modeling | CC BY NC ND 4.0 | CHEMRXIV | 2020-05-13 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/60c74b10337d6c17bee27a03/original/optimization-of-a-new-reactive-force-field-for-silver-based-materials.pdf |
6188b6b492abe0f5d9395b3c | 10.26434/chemrxiv-2021-jvbfl | Hydrogen properties in an organic molecule revealed by XFEL and electron crystallography | Structure analysis of small crystals is important in synthetic organic chemistry, pharmaceutical and material sciences, and related areas, as the conformation of these molecules may differ in large and small crystals, thus affecting the interpretation of their functional properties and drug efficacy. From small crystals, X-ray and electron beams could furnish electron densities and Coulomb potentials of target molecules, respectively. The two beams provide distinctly different information, and this potential has not been fully explored. Here we present the detailed structure of an organic molecule, rhodamine-6g by X-ray free-electron laser (XFEL) and electron crystallography from the same sample batch of microcrystals. This is the first organic molecular structure determined using XFEL at subatomic resolution. Direct comparison between the electron-density and the Coulomb-potential maps together with theoretical models based on Poisson’s equation shows that the position of hydrogen atoms depends on bond type and charge distribution. The combined approach could lead to better insights into their chemical and/or binding properties for a broad range of organic molecules. | Kiyofumi Takaba; Saori Maki-Yonekura; Ichiro Inoue; Kensuke Tono; Tasuku Hamaguchi; Keisuke Kawakami; Hisahi Naitow; Tetsuya Ishikawa; Makina Yabashi; Koji Yonekura | Organic Chemistry; Materials Science; Analytical Chemistry; Analytical Apparatus; Microscopy; Crystallography – Organic | CC BY NC ND 4.0 | CHEMRXIV | 2021-11-09 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/6188b6b492abe0f5d9395b3c/original/hydrogen-properties-in-an-organic-molecule-revealed-by-xfel-and-electron-crystallography.pdf |
60c7414e567dfec904ec3d4e | 10.26434/chemrxiv.8008934.v1 | Multiscale Simulations of Singlet and Triplet Exciton Dynamics in Disordered Molecular Systems based on Many-Body Green’s Functions Theory | <div>We present a multiscale model based on Many-Body Green’s Function Theory in the GW approximation and the Bethe-Salpeter Equation (GW-BSE) for the simulation singlet and triplet exciton transport in molecular materials. Dynamics of coupled electron-hole pairs is modeled as a sequence of incoherent tunneling and decay events in a disordered morphology obtained at room temperature from Molecular Dynamics. The ingredients of the rates associated to the events, i.e., reorganization energies, site energies, lifetimes, and coupling elements, are determined from a combination of GW-BSE and classical polarizable force field techniques. Kinetic Monte Carlo simulations were then employed to evaluate dynamical properties such as the excitonic diffusion tensor and diffusion lengths. Using DCV5T-Me(3,3), a crystalline organic semiconductor, we demonstrate how this multiscale approach provides insight into the fundamental factors driving the transport processes.</div><div>Comparing the results obtained with different calculation models, we investigate in particular the effects of charge-transfer mediated high exciton coupling and the influence of internal site energy disorder due to conformational variations. We show that a small number of high coupling elements indicative of delocalized exciton states does not impact the overall dynamics perceptively. Molecules with energies in the tail of the excitonic density of states dominate singlet decay, independent of the level of disorder taken into account in the simulation. Overall, our approach yields singlet diffusion lengths on the order of 10 nm as expected for disordered molecular materials.</div> | Jens Wehner; Björn Baumeier | Computational Chemistry and Modeling; Theory - Computational | CC BY NC ND 4.0 | CHEMRXIV | 2019-04-19 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/60c7414e567dfec904ec3d4e/original/multiscale-simulations-of-singlet-and-triplet-exciton-dynamics-in-disordered-molecular-systems-based-on-many-body-green-s-functions-theory.pdf |
62b682efe84dd1d29902903d | 10.26434/chemrxiv-2022-gd90m | Reduced Potential Barrier of Sodium-substituted Disordered Rocksalt Cathode for Oxygen Evolution Electrocatalysts | Cation disordered rocksalt (DRX) cathodes have been viewed as next-generation high energy density materials surpassing conventional layered cathodes for lithium-ion battery (LIB) technology. Grabbing the opportunity of a better cation mixing facility in DRX, we synthesize Na-doped DRX as an efficient electrocatalyst toward oxygen evolution reaction (OER). This novel OER electrocatalyst generates a current density of 10 mA cm-2 at an overpotential (η) of 270 mV, Tafel slope of 67.5 mV dec-1, and long-term stability >5.5 days superior to benchmark IrO2 (η = 330 mV with Tafel slope = 74.8 mV dec-1). This superb electrochemical behavior is well supported by experiment and sparse Gaussian process potential (SGPP) machine learning-based search for minimum energy structure. Moreover, as oxygen binding energy (OBE) on the surface closely relates to OER activity, our density functional theory (DFT) calculations reveal that Na-doping assists in facile O2 evolution (OBE = 5.45 eV) compared with pristine-DRX (6.51 eV). | ADITYA NARAYAN SINGH; Amir Hajibabaei; Miran Ha; Abhishek Meena; Kyung-Wan Nam | Catalysis; Base Catalysis; Redox Catalysis; Materials Chemistry | CC BY 4.0 | CHEMRXIV | 2022-12-21 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/62b682efe84dd1d29902903d/original/reduced-potential-barrier-of-sodium-substituted-disordered-rocksalt-cathode-for-oxygen-evolution-electrocatalysts.pdf |
60c74701bdbb895afaa38ce2 | 10.26434/chemrxiv.11474583.v1 | On The Importance of Accurate Algorithms for Reliable Molecular Dynamics Simulations | <div><div><div><p>Molecular dynamics is expected to produce accurate results over a wide range of conditions and timescales. However, this is not always the case since the field has been too reluctant to abandon historically popular techniques known to introduce artefacts. Two recent papers have suggested there are reliability issues in the GROMACS code since it no longer uses a legacy twin-range algorithm. Here, we show there are order-of-magnitude differences in accuracy favoring the modern Trotter decomposition, and that a force field relying on the old algorithm will have errors parametrized into the force field. Similarly, the suggestions about incorrect virial calculations turn out to be explained by insufficient accuracy in the default SHAKE settings used for GROMOS, while the GROMACS default choices are accurate. This highlights the importance of being more critical to error cancellation in simulations in order for algorithms and parameters to both gradually converge to more perfect ones.</p></div></div></div> | Berk Hess; David van der Spoel; Mark J. Abraham; Erik Lindahl | Computational Chemistry and Modeling | CC BY NC 4.0 | CHEMRXIV | 2019-12-31 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/60c74701bdbb895afaa38ce2/original/on-the-importance-of-accurate-algorithms-for-reliable-molecular-dynamics-simulations.pdf |
60c742ecbdbb89627ca3857d | 10.26434/chemrxiv.8847839.v1 | Resorcinarene Cavitand Polymers for the Remediation of Halomethanes and 1,4-Dioxane | <p>Executive summary: Porous resorcinarene-containing polymers are used to remove halomethane disinfection byproducts and 1,4-dioxane from water.<br /></p><p><br /></p><p>Disinfection byproducts such as trihalomethanes are some of the most common micropollutants found in drinking water. Trihalomethanes are formed upon chlorination of natural organic matter (NOM) found in many drinking water sources. Municipalities that produce drinking water from surface water sources struggle to remain below regulatory limits for CHCl<sub>3</sub> and other trihalomethanes (80 mg L<sup>–1</sup> in the United States). Inspired by molecular CHCl<sub>3</sub>⊂cavitand host-guest complexes, we designed a porous polymer comprised of resorcinarene receptors. These materials show higher affinity for halomethanes than a specialty activated carbon used for trihalomethane removal. The cavitand polymers show similar removal kinetics as activated carbon and have high capacity (49 mg g<sup>–1</sup> of CHCl<sub>3</sub>). Furthermore, these materials maintain their performance in real drinking water and can be thermally regenerated under mild conditions. Cavitand polymers also outperform activated carbon in their adsorption of 1,4-dioxane, which is difficult to remove and contaminates many public water sources. These materials show promise for removing toxic organic micropollutants and further demonstrate the value of using supramolecular chemistry to design novel absorbents for water purification.<br /></p> | Luke Skala; Anna Yang; Max Justin Klemes; Leilei Xiao; William Dichtel | Organic Polymers; Polymerization (Polymers); Hydrology and Water Chemistry | CC BY NC ND 4.0 | CHEMRXIV | 2019-07-10 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/60c742ecbdbb89627ca3857d/original/resorcinarene-cavitand-polymers-for-the-remediation-of-halomethanes-and-1-4-dioxane.pdf |
642daa000784a63aee96e2b1 | 10.26434/chemrxiv-2023-6m8s1 | Initial steps in the formation of the solid electrolyte interphase on alkaline metal anodes studied by ab initio simulations | The transition from lithium-based energy storage to post lithium systems plays a crucial part in achieving an environmentally sustainable energy infrastructure. Prime candidates for the replacement of lithium are sodium and potassium batteries. Despite being critical to battery performance, the solid electrolyte interphase (SEI) formation process for Na and K batteries remains insufficiently understood, especially compared to the well-established lithium systems. Using ab initio molecular dynamics (AIMD) simulations based on density functional theory (DFT) calculations, we study the first steps of SEI formation upon the decomposition of typical solvent molecules on lithium, sodium and potassium metal anodes. We find that two dominant products form during the early SEI formation of cyclical carbonates on alkali metal anodes, carbon monoxide and alkali-carbonate. The carbonate-producing reaction is thermodynamically favorable for all tested metals, however, Na and K exhibit a much stronger selectivity than Li towards carbonate formation. Furthermore, we propose a previously unknown reaction mechanism for the CO polymerization on metallic lithium. | Daniel Stottmeister; Axel Gross | Theoretical and Computational Chemistry; Physical Chemistry; Energy; Computational Chemistry and Modeling; Energy Storage | CC BY NC 4.0 | CHEMRXIV | 2023-04-06 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/642daa000784a63aee96e2b1/original/initial-steps-in-the-formation-of-the-solid-electrolyte-interphase-on-alkaline-metal-anodes-studied-by-ab-initio-simulations.pdf |
66a22f8b5101a2ffa8ff7166 | 10.26434/chemrxiv-2024-qjtnf | Ab Initio Molecular Dynamics Study of Trivalent Rare Earth Rich Borate Glasses: Structural Insights and Formation Mechanisms | In this work, trivalent rare earth (RE)-rich borate glasses (30La2O3-70B2O3, 50La2O3-50B2O3, 60La2O3-40B2O3, and 50Y2O3-50B2O3) were modeled using ab initio molecular dynamics (AIMD) simulations through the melt-quenching route. It was found that the AIMD-derived structures reproduced the experimental structure factors and 11B solid-state nuclear magnetic resonance data. Isolated borate units (monomers, dimers, and trimers) terminated with non-bridging oxygen were found in the structures. Polymer units containing four or more boron atoms were identified with and without three-membered boron rings (Bring). Increasing the proportion of La2O3 in La2O3-B2O3 glasses resulted in an increased number of isolated units, indicating that La3+ acts as a network modifier, breaking the borate glass network. The formation of these units via the melt-quenching process was detected by labeling boron species at each AIMD step from $1500$ to 300 K. Representation with transition matrices clarified the specific reaction routes leading to the formation of isolated boron units in solid glass. A key finding is the stabilization of polymer units involving ring formation. The formation of isolated units is achieved through the reaction of polymers without rings. The RE coordination structure was thoroughly analyzed from the perspective of shape and symmetry. Reference structures derived from the solution of the Thomson problem were compared to the AIMD-derived coordination structures and crystalline LaBO3 and YBO3. The results highlight the specificity of the Y coordination structure with rings in YBO3, which is not observed in RE borate glasses. The analytical approaches and interpretations used in this study provide insights into the diverse coordination structures of glasses containing heavy elements other than REs. | Takahiro Ohkubo; Syunta Sasaki; Atsunobu Masuno; Eiji Tsuchida | Physical Chemistry; Inorganic Chemistry; Materials Chemistry | CC BY 4.0 | CHEMRXIV | 2024-07-26 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/66a22f8b5101a2ffa8ff7166/original/ab-initio-molecular-dynamics-study-of-trivalent-rare-earth-rich-borate-glasses-structural-insights-and-formation-mechanisms.pdf |
66748b2d01103d79c5b8f36e | 10.26434/chemrxiv-2024-z6sks | Synthesis of 2-Amino-2-Deoxy Sugars via Boron-Catalyzed Coupling of Glycosyl Fluorides and Silyl Ether Acceptors | Whereas aminosugars are an important component in a variety of bioactive molecules, their stereoselective formation is made challenging by the Lewis basic nature of amino substituents. Additionally, the use of N-acyl protecting groups is often problematic due to competing formation of oxazolines during the glycosylation of 2-aminosugar derivatives. Herein, we report a boron-catalyzed strategy utilizing silyl ether glycosyl acceptors and 2-aminosugar donors that utilize the 2,2,2-trichloroethoxycarbonyl (Troc) protecting group for the C2 amino functionality in glycosyl fluorides. This modification allows for operationally simple, room-temperature glycosylations and features a rapid reaction profile that addresses some of the limitations in the synthesis of 2-amino-2-deoxy sugar containing glycosides. Tailoring the order of reactivity of the silyl acceptors enables one-pot iterative glycosylations, thus streamlining the synthesis of complex oligosaccharides while allowing fewer intermediates and purification steps. | Yishu Xu; John Montgomery | Organic Chemistry; Catalysis; Organic Compounds and Functional Groups; Organic Synthesis and Reactions; Homogeneous Catalysis | CC BY 4.0 | CHEMRXIV | 2024-06-21 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/66748b2d01103d79c5b8f36e/original/synthesis-of-2-amino-2-deoxy-sugars-via-boron-catalyzed-coupling-of-glycosyl-fluorides-and-silyl-ether-acceptors.pdf |
6372463855455ed37d8421ce | 10.26434/chemrxiv-2022-v3txd-v2 | The Old Quantum Theory for One-Electron Diatomic Ions and Molecules |
The modern version of the Old Quantum Theory (OQT) is applied to one-electron diatomic systems in the clamped nucleus approximation. The first part reviews the theory, whose key feature is that only those trajectories whose classical action integrals are integer or half-integer multiples of Planck’s constant are allowed. The OQT is not correct, notoriously so in the case of the ground state of H+2 . Nonetheless, elements of the underlying classical structure have effects on quantum results, an understanding of which may aid in the interpretation of wave functions and energies. In particular, the classical separatracies provide an interpretation for the failure to describe the ground state of H+2 , for kinks in the electronic energy at small internuclear separation, and for quantum critical points. The OQT generates a ground-state Born-Oppenheimer potential energy minimum for the artificial neutral one-electron molecule; for such low quantum numbers, the accuracy is not high, emphasizing the importance of quantum concepts such as superposition of states in the real world. In addition, while accuracy of the classical results does increase with quantum number (Bohr Correspondence Principle), all OQT results show some disagreement with quantum values regardless of quantum number. | Stephen Knudson | Theoretical and Computational Chemistry; Chemical Education | CC BY NC ND 4.0 | CHEMRXIV | 2022-11-15 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/6372463855455ed37d8421ce/original/the-old-quantum-theory-for-one-electron-diatomic-ions-and-molecules.pdf |
62670175742e9f0b336b6b2b | 10.26434/chemrxiv-2022-fqvpf | Liquid Crystal-Templated Porous Microparticles
via Photopolymerisation of Temperature-Induced
Droplets in a Binary Liquid Mixture | Porous polymeric microspheres are an emerging class of materials, offering stimuli-responsive cargo uptake and release. Herein, we describe a new approach to fabricate porous anisotropic microspheres based on temperature-induced droplet formation and light-induced polymerisation. Anisotropic liquid crystal (LC) microparticles were prepared by exploiting the partial miscibility of a thermotropic LC mixture composed of 4-cyano-4’- pentylbiphenyl (5CB, unreactive mesogens) with 2-methyl- 1,4-phenylene bis4-[3-(acryloyloxy)propoxy] benzoate (RM257, reactive mesogens) in methanol (MeOH). Isotropic 5CB/RM257-rich droplets were generated by cooling below the binodal curve (20°C), and the isotropic-to-nematic transition occurred after cooling below 0°C. The resulting 5CB/RM257-rich droplets with radial configuration were subsequently polymerised under UV light, resulting in nematic microparticles. Upon heating the mixture, the 5CB mesogens underwent a nematic-isotropic transition and eventually became homogeneous with MeOH, while the polymerised RM257 preserved its radial configuration. Repeated cycles of cooling and heating resulted in swelling and shrinking of the porous microparticles. The use of a reversible materials templating approach to obtain porous microparticles provides new insights into binary liquid manipulation and potential for microparticle production. | Mehzabin Patel; Alberto Alvarez-Fernandez; Maximiliano Jara Fornerod; Anand Pallipurath Radhakrishnan; Alaric Taylor; Sing Teng Chua; Silvia Vignolini; Benjamin Schmidt-Hansberg; Alexander Iles; Stefan Guldin | Materials Science; Polymer Science; Nanoscience; Liquid Crystals; Materials Processing; Nanostructured Materials - Materials | CC BY NC ND 4.0 | CHEMRXIV | 2022-04-28 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/62670175742e9f0b336b6b2b/original/liquid-crystal-templated-porous-microparticles-via-photopolymerisation-of-temperature-induced-droplets-in-a-binary-liquid-mixture.pdf |
60c743749abda25b9df8c1de | 10.26434/chemrxiv.9201983.v1 | Robust Photopatterning of Gold-Thiol Self-Assembled Monolayers | While photopatterning is in widespread use for patterning inorganic semiconductors, patterning of widely-used gold-thiol organic self-assembled monolayers is typically done with contact methods. Through common atomic force microscope techniques and quantification of the energy impinging on the target surface, the energy required for UV-photooxidation of Au-Thiol SAMs can be determined. This quantification allows for the precise control of features using simple shadow masking from electron microscopy grids or other targets. Beyond characterizing the accuracy and resolution of features, the pattern stability of the resulting monolayers is examined indicating a drive toward phase segregation and increasing order of the mixed monolayers. | Nathaniel Miller; Geoffrey Hutchison | Coating Materials; Materials Processing; Interfaces | CC BY NC ND 4.0 | CHEMRXIV | 2019-08-01 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/60c743749abda25b9df8c1de/original/robust-photopatterning-of-gold-thiol-self-assembled-monolayers.pdf |
63e99c871d2d1840635ec736 | 10.26434/chemrxiv-2023-18c24 | Organobase-catalyzed carboxyl-yne click polymerization | Unsaturated polyester can be directly chemically modified, which provides sufficient feasibility for further functionalization of polymeric polyester, so the simple synthesis of unsaturated polyester is of great significance. We have developed click polymerization of diynes and dicarboxylic acids with DABCO as catalyst. After the optimization of reaction conditions, the poly (carbonyl enol ester) with molecular weight of 24 200 was obtained, and the polymerization yield reached 96%. The synthesis of fat and aromatic poly (carbonyl enol ester) could be realized in different solvents. The polymerization reaction has excellent regioselectivity and stereoselectivity, and the obtained aliphatic unsaturated polycarbonyl enol esters are crystalline polymers. In addition, the polymerization reaction needs mild conditions, short reaction time, can be carried out in air atmosphere, and has low requirements on the purity and types of reaction reagents, and can realize gram-level polymer preparation, thus providing a convenient, efficient and rapid synthetic route for the preparation of enol ester materials. | Han Si; Anjun Qin; Ben Zhong Tang | Polymer Science | CC BY NC ND 4.0 | CHEMRXIV | 2023-02-14 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/63e99c871d2d1840635ec736/original/organobase-catalyzed-carboxyl-yne-click-polymerization.pdf |
65c674d266c13817294db299 | 10.26434/chemrxiv-2024-8jmtn | Developing Measurement-Informed Methane Emissions Inventory Estimates at Midstream Compressor Stations | Natural gas transmissions and storage compressor stations account for the largest share of methane (CH4) emissions in New York State (NYS). Yet, NYS’s CH4 emissions inventory is based on measurements that are a decade old and unlikely to be representative of NYS operations. Here, we present results from a comprehensive, multi-scale aerial CH4 measurement campaign across all NYS transmission and storage compressor stations. We find a skewed emissions distribution, with 20% of stations accounting for 74% of total CH4 emissions. Emissions at engine-driven compressor stations are, on average, 3-4x higher than emissions at turbine-driven compressor stations, thus demonstrating the need for separate emissions factors for engine- and turbine-drive compressor stations. Overall, measurement-informed emissions inventory from midstream transmission and storage compressor stations in NYS are 72% and 69% lower than the current NYS inventory, respectively. We estimate updated emissions factors of 464 [95% CI: 162 – 920] metric ton (MT) CH4/station/yr and 139 [97, 191] MT CH4/station/yr for engine- and turbine-based transmission compressor stations, respectively. Similarly, we estimate an updated emissions factor of 413 [164, 733] MT CH4/station/yr for engine-based storage compressor stations. These updated emissions factors, along with improved activity data, enable effective reconciliation of NYS inventory with measured emissions. | Arvind Ravikumar; Zhongju (Hugh) Li; Shuting (Lydia) Yang; Mackenzie Smith | Energy; Fuels - Energy Science | CC BY NC ND 4.0 | CHEMRXIV | 2024-02-12 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/65c674d266c13817294db299/original/developing-measurement-informed-methane-emissions-inventory-estimates-at-midstream-compressor-stations.pdf |
610d9e2cabc9e223b2681ee7 | 10.26434/chemrxiv-2021-q09gr | A mechanistic investigation of the Pd-catalyzed cross-coupling between N-tosylhydrazones and aryl halides | The cross-coupling of N-tosylhydrazones and aryl halides forms carbon-carbon bonds, producing 1,1-disubstituted alkenes. Though it has proven extremely useful in several fields of chemistry, its mechanism remains experimentally unexplored. Combining benchtop NMR and real-time mass spectrometry afforded the ability to monitor the catalytic intermediates as well as the rate of product formation. | Gilian Thomas; Kiera Ronda; Scott McIndoe | Catalysis; Analytical Chemistry; Organometallic Chemistry; Mass Spectrometry; Kinetics and Mechanism - Organometallic Reactions | CC BY NC ND 4.0 | CHEMRXIV | 2021-08-09 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/610d9e2cabc9e223b2681ee7/original/a-mechanistic-investigation-of-the-pd-catalyzed-cross-coupling-between-n-tosylhydrazones-and-aryl-halides.pdf |
647a328be64f843f4137a29b | 10.26434/chemrxiv-2023-mftg1 | A Near-Infrared Ratiometric Fluorescent Probe for Detecting Endogenous Cu2+ in the Brain | Copper participates in a range of critical functions in the nervous system in the human brain. Disturbances in brain copper content is strongly associated with neurological disease. For example, changes in the level and distribution of copper are reported in neuroblastoma, Alzheimer's disease and Lewy body disorders. There is a need for more sensitive techniques to measure intracellular copper levels to have a better understanding of the role of copper homeostasis in neuronal disorders. Here we report a reaction-based near-infrared (NIR) ratiometric fluorescent probe CyCu1 for imaging Cu2+ in biological samples. High stability and selectivity of CyCu1 enabled the probe to be deployed as a sensor in a range of systems, including SH-SY5Y and neuroblastoma cells. Furthermore, it can be used in plant cells, reporting copper added to Arabidopsis roots. We also used CyCu1 to explore Cu2+ levels and distribution in postmortem brain tissues from patients with the Lewy body disorder, Dementia with Lewy bodies (DLB). We found significant decreases in Cu2+ content in the nuclei, cytoplasm, neurons and extraneuronal space in the degenerating substantia nigra (SN) in DLB compared with healthy age-matched control tissues. These findings enhance our understanding of Cu2+ dysregulation in Lewy body disorders. Our probe also shows promise as a photoacoustic imaging agent, with potential for applications in bimodal imaging. | Jianping Zhu; Marcus E. Graziotto; Veronica Cottam; Tom Hawtrey; Jourdin R. C. Rouaen; Carolyn Ohno; Marcus Heisler; Orazio Vittorio; Kay L. Double; Elizabeth J. New | Biological and Medicinal Chemistry; Organic Chemistry; Biochemistry | CC BY NC ND 4.0 | CHEMRXIV | 2023-06-07 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/647a328be64f843f4137a29b/original/a-near-infrared-ratiometric-fluorescent-probe-for-detecting-endogenous-cu2-in-the-brain.pdf |
64f0c3043fdae147fa3585d7 | 10.26434/chemrxiv-2023-k6k7m | Electrochemistry of Gadolinium-Polyoxometalate Complexes in Concentrated Salt Solutions | Lanthanide-polyoxometalate complexes have been recently shown to possess unique magnetic, luminescent, and catalytic properties. While their electrochemical behavior has been explored in literature to some degree, the role of metallic spe-cies within the POM and nature and concentration of counter-cations in solutions has not been fully explained. The cur-rent work seeks to address this by studying the Gd(OTf)3 – [H2W12O40]6-(MT) – Si(W12O40)-4 system in concentrated LiCl in N,N-dimethylformamide (DMF) using electrochemical and spectroscopic techniques. It was found that Gd3+ did not chem-ically bond to the POM species but interacted electrostatically through the Ot bonds of the MT POM but not Si based POM. Electrochemically, Gd3+ showed more reversible electrochemistry but was able to gain an additional electron in the pres-ence of the MT- species. The Si-POM did not show much electrochemical behavior in the presence of Li+ and Gd3+ likely due to its non-interaction with both species, found using FTIR. The current work presents a step forward in the under-standing of the role of metallic and cationic species in the electrochemical behavior of lanthanide-POM complexes. | Luke Soule; Mary Louise Gucik; Jamin Pillars; Christian Arrington | Inorganic Chemistry | CC BY 4.0 | CHEMRXIV | 2023-09-01 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/64f0c3043fdae147fa3585d7/original/electrochemistry-of-gadolinium-polyoxometalate-complexes-in-concentrated-salt-solutions.pdf |
652683c18bab5d20551c0a92 | 10.26434/chemrxiv-2023-03s0m-v2 | BASHY Dyes Are Highly Efficient Lipid Droplet-targeting Photosensitizers That Induce Ferroptosis Through Lipid Peroxidation | Ferroptosis is an iron-dependent lipid peroxidation-driven mechanism of cell death and a promising therapeutic target to eradicate cancer cells. In this study we discovered that boronic acid derived salicylidenehydrazone (BASHY) dyes are highly efficient singlet-oxygen photosensitizers (PSs; quantum yields up to 0.8) that induce ferroptosis triggered by photodynamic therapy. The best performing BASHY dye displayed a high phototoxicity against the human glioblastoma multiform U87 cell line, with an IC50 value in the low nanomolar range (4.40 nM) and a remarkable phototoxicity index (PI > 22700). Importantly, BASHY dyes were shown to accumulate in lipid droplets and this intracellular partition was found to be essential for the enhanced phototoxicity and the induction of ferroptosis through lipid peroxidation. The safety and phototoxcity of this platform were validated in in vivo studies on zebrafish embryos (Danio rerio). | Maria Silva; Yiyi Zhang; Robin Vinck; Fábio Santos; João António; Lisa Gourdon-Grünewaldt; Charlotte Zaouter; Annie Castonguay; Shunmoogum Patten; Kevin Cariou; Francisco Boscá; Francisco Nájera; Jesús Arteaga; Gilles Gasser; Uwe Pischel; Pedro Gois | Biological and Medicinal Chemistry; Chemical Biology; Drug Discovery and Drug Delivery Systems | CC BY NC ND 4.0 | CHEMRXIV | 2023-10-11 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/652683c18bab5d20551c0a92/original/bashy-dyes-are-highly-efficient-lipid-droplet-targeting-photosensitizers-that-induce-ferroptosis-through-lipid-peroxidation.pdf |
66470f8291aefa6ce13a816e | 10.26434/chemrxiv-2024-4kk6v | Analysis of the change in molecular complexity of reaction products in process development activities at AstraZeneca over time. | The assessment of molecular complexity of active pharmaceutical ingredients (APIs) can help guide decisions within drug development, for example by correlation to sustainability targets, project resource requirements and predicted development and manufacturing timelines. However, such quantifications are limited by the challenge of defining complexity itself, as well as the small sample size of API molecules making longer term comparisons challenging. We have used three complementary approaches to calculate the complexity of reaction products of more than 165 000 reaction entries across our process development electronic laboratory notebooks. Importantly, this covers both intermediates, APIs, and other molecules requiring synthesis, thus attempts to provide an analysis of reaction products from all out synthetic chemistry activities. This information facilitated the investigation of changes in the mean values of different measures of molecular complexity per year between 2007-2020. We discuss the insights these quantifications reveal, and how this analysis may be of more general use in understanding the diversity of the molecules in our process development portfolio. | George Karageorgis; James Douglas; Gareth Howell | Organic Chemistry; Process Chemistry | CC BY NC 4.0 | CHEMRXIV | 2024-05-17 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/66470f8291aefa6ce13a816e/original/analysis-of-the-change-in-molecular-complexity-of-reaction-products-in-process-development-activities-at-astra-zeneca-over-time.pdf |
6465a5f8fb40f6b3eec2aaa7 | 10.26434/chemrxiv-2023-8qvwg | Autonomous MicroED data collection enables compositional analysis | MicroED is an effective method for analyzing the structural properties of sub-micron crystals, which are frequently found in small-molecule powders. By developing and using an autonomous and high throughput approach to MicroED, we demonstrate the expansion of capabilities and the possibility of performing complete compositional analysis of complex samples. With the use of SerialEM for data collection of thousands of datasets from thousands of crystals and an automated processing pipeline, compositional analysis of complex mixtures of organic and inorganic compounds can be accurately executed. Quantitative analysis suitable for compounds having similar chemical properties can be made on the fly. These compounds can be distinguished by their crystal structure properties prior to structure solution. Additionally, with sufficient statistics from the autonomous approach, even small amounts of compounds in mixtures can be reliably detected. Finally, atomic structures can be determined from the thousands of data sets. | Johan Unge; Jieye Lin; Sara J Weaver; Ampon Sae Her; Tamir Gonen | Analytical Chemistry; Analytical Chemistry - General | CC BY 4.0 | CHEMRXIV | 2023-05-18 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/6465a5f8fb40f6b3eec2aaa7/original/autonomous-micro-ed-data-collection-enables-compositional-analysis.pdf |
60c74846567dfe3f9cec499d | 10.26434/chemrxiv.11874816.v1 | Large-Scale Free Energy Calculations on a Computational MOF Database: Toward Synthetic Likelihood Predictions | Metal-organic frameworks (MOFs) have captivated the research community due to a modular crystal structure that is tailorable for many applications. However, with millions of possible MOFs to be considered, it is challenging to identify the ideal MOF for the application of choice. Although computational screening of MOF databases has provided a fast way to evaluate MOF properties, validation experiments on predicted “exceptional” MOFs are not common due to uncertainties on the synthetic likelihood of computationally constructed MOFs, hence hindering material discovery. Aiming to leverage the perspective provided by large datasets, here we created and screened a topologically diverse database of 8,500 MOFs to interrogate whether thermodynamic stability metrics such as free energy could be used to generally predict the synthetic likelihood of computationally constructed MOFs. To this end, we first evaluated the suitability of two methods and three force fields to calculate free energies in MOFs at large scale, settling on the Frenkel-Ladd path thermodynamic integration method and the UFF4MOF force field. Upon defining a relative free energy, Δ<sub>LM</sub>F<sub>FL</sub>, that corrects for some force field artifacts specific to MOF nodes, we found that previously synthesized MOFs tended to cluster in a region below Δ<sub>LM</sub>F<sub>FL</sub> = 4.4 kJ/mol per atom, suggesting a general first filter to discriminate between synthetically likely and unlikely MOFs. However, a second filter is needed when several MOF isomorphs are below the Δ<sub>LM</sub>F<sub>FL</sub> threshold. In 84% of the cases, the synthetically accessible MOF within an isomorphic series presented the lowest predicted free energy. The present; work suggests that crystal free energies could be key to understanding synthetic likelihood for MOFs in computational databases (and MOFs in general), and that the thermodynamics stability of the fully assembled MOF often determines synthetic accessibility. | Ryther Anderson; Diego Gómez-Gualdrón | Hybrid Organic-Inorganic Materials; Theory - Computational | CC BY NC ND 4.0 | CHEMRXIV | 2020-02-21 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/60c74846567dfe3f9cec499d/original/large-scale-free-energy-calculations-on-a-computational-mof-database-toward-synthetic-likelihood-predictions.pdf |
6582a86566c1381729a0ad9d | 10.26434/chemrxiv-2023-7m13d | 2’,3’-protected nucleotides as building blocks for enzymatic de novo RNA synthesis | Besides being a key player in numerous, fundamental biological process, RNA also represents a versatile platform for the creation of therapeutic agents and efficient vaccines. The production of RNA oligonucleotides, especially those decorated with chemical modifications, cannot meet the exponential demand. Due to the inherent limits of solid-phase synthesis and in vitro transcription, alternative, biocatalytic approaches are in dire need to facilitate the production of RNA oligonucleotides. Here, we present a first step towards the controlled enzymatic synthesis of RNA oligonucleotides. We have explored the possibility of a simple protection step of the vicinal cis-diol moiety to temporarily block ribonucleotides. We demonstrate that pyrimidine nucleotides protected with acetals, particularly 2',3'-O-isopropylidene, are well-tolerated by the template-independent RNA polymerase PUP (polyU polymerase) and highly efficient coupling reactions can be achieved within minutes – an important feature for the development of enzymatic de novo synthesis protocols. Even though purines are not equally well-tolerated, these findings clearly demonstrate the possibility of using cis-diol-protected ribonucleotides combined with template-independent polymerases for the stepwise construction of RNA oligonucleotides. | Maëva Pichon; Fabienne Levi-Acobas; Camélia Kitoun; Marcel Hollenstein | Biological and Medicinal Chemistry; Organic Chemistry; Bioorganic Chemistry; Chemical Biology | CC BY NC ND 4.0 | CHEMRXIV | 2023-12-26 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/6582a86566c1381729a0ad9d/original/2-3-protected-nucleotides-as-building-blocks-for-enzymatic-de-novo-rna-synthesis.pdf |
6537f5d6c3693ca993071341 | 10.26434/chemrxiv-2023-ql8pk | The Dianion and Tetraanion of [18]Annulene | [18]Annulene, (CH)18, is one of the iconic molecules of organic chemistry. Sondheimer’s investigation of this compound in the 1960s provided a compelling endorsement for molecular orbital theory by showing that Hückel’s rule extends to molecules substantially larger than benzene. Molecules with circuits of 4n+2 π-electrons, such as [18]annulene (n = 4), are aromatic, with enhanced stability and diatropic ring currents (magnetic shielding inside the ring), whereas those with 4n π-electrons are antiaromatic and exhibit the opposite behaviour. In 1973, Oth, Woo and Sondheimer reported that [18]annulene can be reduced to an antiaromatic dianion (20 π-electrons). Here we show that their published structural assignment of this dianion was incorrect, and that [18]annulene can also be reduced to a stable aromatic tetraanion (24 π-electrons). The 1H NMR spectra of the dianion and tetraanion confirm that they are antiaromatic and aromatic, respectively, and indicate that [18]annulene adopts a C2v conformation in both reduced states that contrasts the virtual D6h symmetry of the neutral ring. The crystal structure of the tetraanion lithium salt confirms this geometry and reveals a metallocene-like sandwich, with five Li+ cations intercalated between two [18]annulene tetraanions. We also report a heteroleptic sandwich, with both [18]annulene and corannulene tetraanion decks. | Wojciech Stawski; Yikun Zhu; Igor Rončević; Zheng Wei; Marina Petrukhina; Harry Anderson | Theoretical and Computational Chemistry; Organic Chemistry; Organic Compounds and Functional Groups; Physical Organic Chemistry; Crystallography – Organic | CC BY NC 4.0 | CHEMRXIV | 2023-10-25 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/6537f5d6c3693ca993071341/original/the-dianion-and-tetraanion-of-18-annulene.pdf |
66e71746cec5d6c14226da73 | 10.26434/chemrxiv-2024-t80qn | Investigations of Enteric-Coated Propyl Gallate-induced Nephrotoxicity in Beagles and Human and Dog Renal Proximal Tubule Epithelial Cells | Permeability plays a major role in oral biotherapeutic delivery and permeation enhancers can improve the intestinal permeability of poorly absorbed active pharmaceutical ingredients such as peptides. As part of nonclinical development of an oral formulation for a glucagon-like peptide-1 (GLP-1) receptor agonist, MEDI7219, toxicology studies revealed that one of the formulation excipients, propyl gallate (PG), when administered in enteric-coated tablets, led to nephrotoxicity in beagles. While PG has been widely used in food and cosmetics as an anti-oxidant, understanding of its toxicology, metabolism and disposition has been rarely discussed. To elucidate the nephrotoxicity observed after administration of PG in an enteric coated tablet formulation, we employed dog and human renal proximal tubule epithelial cells (RPTEC). We observed greater cytotoxicity to PG in dog RPTEC compared to human cells. We also observed greater increases in response to PG treatment of glutathione in human cells compared to dog cells. Glutathione elevation is a common response to detoxify xenobiotics, especially ones that produce free radicals such as PG. Thus, we hypothesize that glutathione in human RPTECs was elevated to detoxify PG, but not in dog RPTECs, leading to greater cytotoxicity for dog RPTECs. Furthermore, to characterize disposition and metabolism of PG in both humans and dogs we developed a 10-plex, highly sensitive and robust LC-MS/MS-based quantification method of PG and its phase-I and phase-II metabolites in dog and human plasma. The methods were employed to support clinical study (NCT03362593) and preclinical dog studies to evaluate safety, pharmacokinetics and tolerability of PG to support its use in an oral formulation for MEDI7219. | Si Mou; Brian Timothy Hummer; Jiaqi Yuan; Yue Huang; Meina Liang; Raffaella Faggioni; Lorin K. Roskos; Anton I. Rosenbaum | Biological and Medicinal Chemistry; Analytical Chemistry; Biochemical Analysis; Mass Spectrometry; Chemical Biology | CC BY 4.0 | CHEMRXIV | 2024-09-17 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/66e71746cec5d6c14226da73/original/investigations-of-enteric-coated-propyl-gallate-induced-nephrotoxicity-in-beagles-and-human-and-dog-renal-proximal-tubule-epithelial-cells.pdf |
649f548c6e1c4c986b9be140 | 10.26434/chemrxiv-2023-3fjl6 | Unexpected metabolic rewiring of CO2 fixation in H2-mediated materials-biology hybrids | A hybrid approach combining water-splitting electrochemistry and H2-oxidizing, CO2-fixing microorganisms offers a viable solution of producing value-added chemicals from sunlight, water, and air. The classic wisdom without thorough examination to date assumes that the electrochemistry in such a H2-mediated process is innocent of altering microbial behavior. Here we report unexpected metabolic rewiring induced by water-splitting electrochemistry in H2-oxidizing acetogenic bacterium Sporomusa ovata that challenges such a classic view. We found that the planktonic S. ovata is more efficient in utilizing reducing equivalent for ATP generation and hence CO2 fixation in the materials-biology hybrids, supported by our metabolomic and proteomic studies. These observations unravel previously underappreciated materials’ impact on microbial metabolism in seemingly simply H2-mediated charge transfer between biotic and abiotic components. Such a deeper understanding at the materials-biology interface will foster advanced design of hybrid systems for sustainable chemical transformation. | Yongchao Xie; Sevcan Erşan; Xun Guan; Jingyu Wang; Jihui Sha; Shuangning Xu; James A. Wohlschlegel; Junyoung O. Park; Chong Liu | Biological and Medicinal Chemistry; Catalysis; Microbiology; Biocatalysis; Electrocatalysis; Materials Chemistry | CC BY NC ND 4.0 | CHEMRXIV | 2023-07-05 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/649f548c6e1c4c986b9be140/original/unexpected-metabolic-rewiring-of-co2-fixation-in-h2-mediated-materials-biology-hybrids.pdf |
64829c3d4f8b1884b70a2c92 | 10.26434/chemrxiv-2023-7qf49 | Influence of carbon fiber topographical roughness in epoxy based composite interfaces | The interface between carbon fiber and polymer matrix is a critical aspect of ultimate mechanical performance in carbon fiber reinforced composites. Molecular dynamics simulations have been instrumental in elucidating molecular-level details of the fiber-matrix interface, and have informed surface treatments that enhance interfacial shear strength. Almost all prior simulation efforts used few-layer graphite as a carbon fiber surrogate, and hence have yet to predict realistic mechanical response under shear load conditions for realistic pristine fiber-matrix interfaces. Here, atomistic carbon fiber surface models that feature intrinsic topographical complexity are interfaced with a typical epoxy resin to capture the influence of surface roughness at the composite interface. Both the lengthscale and character of carbon fiber surface roughness is found to affect the structuring of the liquid precursor epoxy, leading to changes in the cured network. Substrate displacement simulations of rough composites yield physically reasonable values of interfacial shear stress compared with previously published data for functionalized composite interfaces, providing a benchmark for future simulation work. The results suggest that treatments such as oxidation and functionalization may be impacted by the presence of intrinsic carbon fiber surface roughness, and should be accounted for in future simulations. | Filip Vuković; Tiffany R. Walsh | Materials Science; Composites; Fibers | CC BY NC 4.0 | CHEMRXIV | 2023-06-09 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/64829c3d4f8b1884b70a2c92/original/influence-of-carbon-fiber-topographical-roughness-in-epoxy-based-composite-interfaces.pdf |
60c742524c891973dcad242b | 10.26434/chemrxiv.8256035.v1 | Henderson Hasselbalch Relationship and Weak Acid Titration | Henderson-Hasselbalch relation is generally the simplified theoretical framework used to introduce students to acid-base titration. However, it is not always valid and its limitations should be made clear to chemistry students. The appropriate parameter to evaluate its validity is K a /C 0 , in connection with Ostwald dilution law. For more advanced students, it is possible to deduce analytical expressions that always fit accurately acid-base titrations and allow an evaluation of Henderson Hasselbalch relation. Gran plot appears as a particularly sensitive technique to the breakdown of Henderson Hasselbalch relation. | Marc Blétry | Chemical Education - General | CC BY NC ND 4.0 | CHEMRXIV | 2019-06-12 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/60c742524c891973dcad242b/original/henderson-hasselbalch-relationship-and-weak-acid-titration.pdf |
60c75801337d6cd172e29130 | 10.26434/chemrxiv.14485224.v1 | Benzodithiophene Fused Cyclopentannulated Aromatics via a Palladium-Catalyzed Cyclopentannulation and Scholl Cyclodehydrogenation Strategy | We report the synthesis of a new class of cyclopenta-fused polyaromatic hydrocarbon (CP-PAH) incorporating fused benzodithiophene subunits. These CP-PAHs were prepared utilizing a two-step process involving a palladium catalyzed cyclopentannulation followed by a Scholl cyclodehydrogenation. This work broadens the scope of annulation chemistry by employing 1,2-bis(5-hexylthiophen-3-yl)ethyne and dibromoaryl derivatives based on anthracene, pyrene and perylene to give 4,4',4'',4'''-(cyclopenta[hi]aceanthrylene-1,2,6,7-tetrayl)tetrakis(2-hexylthiophene) , 4,4',4'',4'''-(dicyclopenta[cd,jk]pyrene-1,2,6,7-tetrayl)tetrakis(2-hexylthiophene) and 1,2,7,8-tetrakis(5-hexylthiophen-3-yl)-1,2,7,8-tetrahydrodicyclopenta[cd,lm]perylene. Scholl cyclodehydrogenation of the pendant thiophene units provided access to the -extended polyaromatic systems 2,5,11,14-tetrahexylrubiceno[5,4-b:6,7-b':12,11-b'':13,14-b''']tetrathiophene, 2,5,11,14-tetrahexyldithieno-[4,5:6,7]indeno[1,2,3-cd]dithieno[4,5:6,7]indeno-[1,2,3-jk]pyrenes, and 2,9,12,19-tetrahexyldithieno[4,5:6,7]indaceno[1,2,3-cd]dithieno[4,5:6,7]indaceno[1,2,3-lm]perylene that possess helicene-like fragments. The anthracene-based CP-PAH was contorted owing to [5]helicene-like arrangements while the pyrene and perylene-based systems were essentially planar. The fully conjugated small molecules give low optical gaps (1.7 - 2.1 eV) with broad light absorption. The HOMO and LUMO energies of the CP-PAHs were found to be in the range of -5.48 to -5.05 eV and -3.48 to -3.14 eV, respectively. Finally, the anthracene-based CP-PAH was found to be a p-type semiconductor when tested in an organic field effect transistor. | Waseem A. Hussain; Kyle Plunkett | Organic Synthesis and Reactions; Physical Organic Chemistry | CC BY NC ND 4.0 | CHEMRXIV | 2021-04-28 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/60c75801337d6cd172e29130/original/benzodithiophene-fused-cyclopentannulated-aromatics-via-a-palladium-catalyzed-cyclopentannulation-and-scholl-cyclodehydrogenation-strategy.pdf |
6385a5ae0949e1130d59dbc0 | 10.26434/chemrxiv-2022-m6nv8-v2 | Photosensitizer Free Visible Light Synthesis of Multifunctional Coumarins from Trans-hydroxy acrylates | A photosensitive and transition metal-free technique without inert gas shielding is reported for the facile synthesis of multifunctional coumarins. The current proce-dure avoids the inherent drawbacks of the previous coumarin production protocol in the presence of transition metal. The prominent aspects of the methodology also include the absence of photocatalyst, the absence of external additives including transition metals, and the employment of a straightforward precursor. Additionally, we went into great detail on the mechanistic investigation and utilization of multi-functional coumarins. | Niladri Sekhar Roy; Biswajit Das; Debayan Sarkar | Organic Chemistry; Catalysis; Homogeneous Catalysis; Photocatalysis | CC BY NC ND 4.0 | CHEMRXIV | 2022-11-29 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/6385a5ae0949e1130d59dbc0/original/photosensitizer-free-visible-light-synthesis-of-multifunctional-coumarins-from-trans-hydroxy-acrylates.pdf |
634df1da339972ffdd8ea13d | 10.26434/chemrxiv-2022-dnf52 | Size dependence of optical nonlinearity for H-capped carbon chains, H-(C≡C)n-H: Analysis of its nature and prediction for long chains | Based on the computational approach that can accurately describe their geometric structures and electronic spectra, we have theoretically studied the nonlinear optical (NLO) properties of H-capped carbon chains, H-(C≡C)n-H, for the first time. Special attention was paid to the size dependence of the molecular (hyper)polarizability of these species through nonlinear fitting of the data, which was thoroughly discussed at the electronic structure level by in-depth wavefunction analyses. The results are expected to provide theoretical guidance for the property prediction of arbitrarily long carbon chains not yet synthesized. | Zeyu Liu; Jiaojiao Wang; Qing Zhou; Tian Lu; Xia Wang; Xiufen Yan; Mengdi Zhao; Aihua Yuan | Theoretical and Computational Chemistry; Computational Chemistry and Modeling | CC BY 4.0 | CHEMRXIV | 2022-10-19 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/634df1da339972ffdd8ea13d/original/size-dependence-of-optical-nonlinearity-for-h-capped-carbon-chains-h-c-c-n-h-analysis-of-its-nature-and-prediction-for-long-chains.pdf |
6630f32821291e5d1d16e271 | 10.26434/chemrxiv-2024-z8lqq | Organocatalytic hydroboration of carbonyl compounds promoted by choline-based ionic liquids | The organocatalytic activity of choline-based ionic liquids in the hydroboration of ketones, aldehydes and carboxylic acids with pinacolborane was investigated. The method employed was based on a simple, inexpensive, biobased, reusable and environmentally friendly [Cho][OAc] catalyst. Detailed studies on catalyst screening, the optimization of reaction conditions, and substrate scope were carried out. [Cho][OAc] showed excellent tolerance to various functional groups and chemoselectivity towards C=O hydroboration, which occurred under mild conditions. Furthermore, it was shown that the reaction can be carried out under repetitive batch modes, allowing effective catalyst recycling and improving process productivity. | Barbara Krupa; Mateusz Nowicki; Paweł Huninik; Jakub Szyling; Jedrzej Walkowiak | Organic Chemistry; Catalysis; Organometallic Chemistry; Homogeneous Catalysis; Organocatalysis | CC BY NC ND 4.0 | CHEMRXIV | 2024-05-02 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/6630f32821291e5d1d16e271/original/organocatalytic-hydroboration-of-carbonyl-compounds-promoted-by-choline-based-ionic-liquids.pdf |
647a738ee64f843f4139ff97 | 10.26434/chemrxiv-2023-mjsz8 | Metabolomics reveals a unique CYP3A-mediated C(sp3)-C(sp2) bond cleavage via ipso-addition reaction in drug metabolism | Cytochrome P450-mediated carbon–carbon (C-C) cleavages are unusual, especially for mammalian drug metabolizing enzymes. Revealing the unusual reactions in biological system is very arduous and selectively oxidative C-C cleavage is also a long-standing challenge in chemistry and biology. We herein present a rapid and efficient metabolomic-based approach to uncover human CYP3A-mediated non-polar, unstrained C(sp2)-C(sp3) bond cleavage in the CSF-1R inhibitor pexidartinib. Using synthetic metabolites, 18O2, and H218O, we demonstrate that one unique cleavage is via the ipso-addition reaction. This is the first report of CYP3A-mediated ipso-addition reaction to the 5-alkylated N-protected pyridin-2-amines. We have expanded the range of substrates undergoing CYP3A-mediated ipso-addition reactions beyond para-phenols to include N-protected alkylated pyridine-2-amines. Our metabolomic-based approach also successfully discovered the CYP3A-mediated C(sp2)-C(sp3) bond cleavage of PEX analogs as well as the antidepressant nefazodone. This work established an efficient strategy to identify the uncommon reactions in drug metabolism using a metabolomic strategy. More importantly, the environmentally friendly conditions of CYP3A-catalyzed unusual ispo-addition reactions hold the potential to inspire future exploration of biomimetic P450-reprogramming methods for addressing the challenging task of unactivated C-C bond cleavage in the field. | Feng Li; Xuan Qin; Yong Wang ; Kevin Mackenzie; Qiuji Ye; John M. Hakenjos; Jin Wang; Mingxing Teng; Lei Guo; Zhi Tan; Damian W. Young | Biological and Medicinal Chemistry | CC BY NC 4.0 | CHEMRXIV | 2023-06-05 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/647a738ee64f843f4139ff97/original/metabolomics-reveals-a-unique-cyp3a-mediated-c-sp3-c-sp2-bond-cleavage-via-ipso-addition-reaction-in-drug-metabolism.pdf |
6438281108c86922ffeb681b | 10.26434/chemrxiv-2023-fcl8s-v2 | Predicting Magnetic Coupling and Spin-Polarization Energy in Triangulene Analogues | Triangulene and its analogue metal-free magnetic systems have garnered increasing attention since their discovery. Predicting the magnetic couplings and spin polarization energy with quantitative accuracy is beyond the predictive power of today’s density-functional theory (DFT) due to their intrinsic multi-reference character. Herein, we create a benchmark dataset of 25 magnetic systems with non-local spin densities, including the triangulene monomer, dimer, and their analogues. We calculate the magnetic coupling (J) and spin-polarization energy (ΔEspin) of these systems using complete active space self-consistent field (CASSCF) and coupled cluster methods as high-quality reference values. This reference data is then used to benchmark 22 DFT functionals commonly used in material science. Our results show that, while some functionals consistently correctly predict the qualitative character of the ground state, achieving quantitative accuracy with small relative errors is currently not feasible. PBE0, M06-2X, and MN15 are predicting the correct electronic ground state for all systems investigated here, and also have the lowest mean absolute error for predicting both ΔEspin (0.34 eV, 0.32 eV and 0.31 eV) and J (11.74 meV, 12.66 meV and 10.64 meV). They may therefore also serve as starting points for higher-level methods such as the GW or the random phase approximation. As other functionals fail for the prediction of the ground state, they cannot be recommended for metal-free magnetic systems. | Hongde Yu; Jianwei Sun; Thomas Heine | Theoretical and Computational Chemistry; Computational Chemistry and Modeling; Theory - Computational | CC BY 4.0 | CHEMRXIV | 2023-04-17 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/6438281108c86922ffeb681b/original/predicting-magnetic-coupling-and-spin-polarization-energy-in-triangulene-analogues.pdf |
640b3a6ee53eff1af3e800a9 | 10.26434/chemrxiv-2023-qlp1h | Post-synthetic Transformation of Imine- into Nitrone-linked Covalent Organic Frameworks for Atmospheric Water Harvesting at Decreased Humidity | Herein, we report a facile post-synthetic linkage conversion method giving synthetic access to nitrone-linked covalent organic frameworks from imine- and amine-linked COFs. The new, 2D nitrone-linked covalent organic frameworks, NO-PI-3-COF and NO-TTI-COF are obtained with high crystallinity and large surface areas. Nitrone-modified pore channels induce capillary condensation of water vapor at 20% lower humidity compared to their amine- or imine-linked precursor COFs. Thus, the topochemical transformation to nitrone linkages constitutes an attractive approach to post-synthetically fine-tune water adsorption properties in framework materials. | Lars Grunenberg; Gökcen Savasci; Sebastian Emmerling; Fabian Heck; Afonso Cima Bergesch; Christian Ochsenfeld; Bettina Lotsch | Organic Chemistry; Nanoscience; Supramolecular Chemistry (Org.); Nanostructured Materials - Nanoscience; Materials Chemistry | CC BY NC ND 4.0 | CHEMRXIV | 2023-03-13 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/640b3a6ee53eff1af3e800a9/original/post-synthetic-transformation-of-imine-into-nitrone-linked-covalent-organic-frameworks-for-atmospheric-water-harvesting-at-decreased-humidity.pdf |
61684497be107474529cb137 | 10.26434/chemrxiv-2021-585ks-v2 | Open Science Discovery of Oral Non-Covalent SARS-CoV-2 Main Protease Inhibitors
| The COVID-19 pandemic is a stark reminder that a barren global antiviral pipeline has grave humanitarian consequences. Future pandemics could be prevented by accessible, easily deployable broad-spectrum oral antivirals and open knowledge bases that derisk and accelerate novel antiviral discovery and development. Here, we report the results of the COVID Moonshot, a fully open-science structure-enabled drug discovery campaign targeting the SARS-CoV-2 main protease. We discovered a novel chemical scaffold that is differentiated to current clinical candidates in terms of toxicity and pharmacokinetics liabilities, and developed it into orally-bioavailable inhibitors with clinical potential. Our approach leverages crowdsourcing, high throughput structural biology, machine learning, and exascale molecular simulations. In the process, we generated a detailed map of the structural plasticity of the main protease, extensive structure-activity relationships for multiple chemotypes, and a wealth of biochemical activity data. In a first for a structure-based drug discovery campaign, all compound designs (>18,000 designs), crystallographic data (>500 ligand-bound X-ray structures), assay data (>10,000 measurements), and synthesized molecules (>2,400 compounds) for this campaign were shared rapidly and openly, creating a rich open and IP-free knowledgebase for future anti-coronavirus drug discovery. | The COVID Moonshot Consortium; John Chodera; Alpha Lee; Nir London; Frank von Delft | Biological and Medicinal Chemistry; Drug Discovery and Drug Delivery Systems | CC BY NC ND 4.0 | CHEMRXIV | 2021-10-19 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/61684497be107474529cb137/original/open-science-discovery-of-oral-non-covalent-sars-co-v-2-main-protease-inhibitors.pdf |
6698a98d01103d79c54ef88a | 10.26434/chemrxiv-2024-fvjn1-v3 | Ortho-functionalized pyridinyl-tetrazines - breaking the inverse correlation between click reactivity and cleavage yields in click-to-release | The bioorthogonal tetrazine-triggered cleavage of trans-cyclooctene(TCO)-linked payloads has strong potential for widespread use in drug delivery and in particular in click-cleavable ADCs, but clinical translation is hampered by an inverse correlation between click reactivity and payload release yield. This requires the use of high doses of relatively less reactive tetrazines to drive in vivo TCO reactions to completion and achieve sufficient payload release. Herein we report that the main cause for the low release when using the highly reactive bis-(2-pyridinyl)-tetrazine is the stability of the initially formed 4,5-dihydropyridazine product, precluding tautomerization to the releasing 1,4-dihydropyridazine tautomer. We demonstrate that efficient tautomerization and payload elimination can be achieved by ortho-substituting bis-pyridinyl-tetrazines with hydrogen-bonding hydroxyl or amido groups, thereby achieving a.o. release yields of 96 % with 18-fold more reactive tetrazines. Applied to on-tumor activation of a click-cleavable ADC in mice, the new tetrazines afforded near-quantitative ADC conversion at a ca. 10- to 20-fold lower dose than what was previously needed, resulting in a strong therapeutic response. | Ron Versteegen; Raffaella Rossin; Ivo Filot; Freek Hoeben; Arthur van Onzen; Henk Janssen; Marc Robillard | Biological and Medicinal Chemistry; Organic Chemistry; Bioorganic Chemistry; Chemical Biology; Drug Discovery and Drug Delivery Systems | CC BY NC ND 4.0 | CHEMRXIV | 2024-07-18 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/6698a98d01103d79c54ef88a/original/ortho-functionalized-pyridinyl-tetrazines-breaking-the-inverse-correlation-between-click-reactivity-and-cleavage-yields-in-click-to-release.pdf |
62e7d481d131b7625b089c5f | 10.26434/chemrxiv-2022-zb85t | Archaeal glycerolipids are recognized by C-type lectin receptor Mincle | Recently, various metabolites derived from host microbes have been reported to modulate the immune system, with potential involvement in health or diseases. Archaea, prokaryotic organisms, are present in the human body, but their connection with the host is largely unknown when compared with other microorganisms such as bacteria. This study focused on unique glycerolipids from symbiotic methanogenic archaea and evaluated their activities toward an innate immune receptor. The results revealed that archaeal lipids were recognized by the C-type lectin receptor Mincle and induced immune responses. A concurrent structure-activity relationship study identified key structural features of archaeal lipids required for recognition by Mincle. Subsequent gene expression profiling suggested qualitative differences between the symbiotic archaeal lipid and the pathogenic bacteria-derived lipid. These findings have broad implications for understanding the function and pathogenicity of symbiotic archaea to host health and diseases. | Shiori Oka; Miyuki Watanabe; Emi Ito; Ami Takeyama; Takuro Matsuoka; Norihito Arichi; Hiroaki Ohno; Sho Yamasaki; Shinsuke Inuki | Biological and Medicinal Chemistry; Chemical Biology | CC BY NC ND 4.0 | CHEMRXIV | 2022-08-02 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/62e7d481d131b7625b089c5f/original/archaeal-glycerolipids-are-recognized-by-c-type-lectin-receptor-mincle.pdf |
60c73f36469df4b23bf42a2c | 10.26434/chemrxiv.7275005.v1 | Large-Amplitude, High-Frequency Single-Molecule Switch | We use a scanning tunneling microscope to form and electrically interrogate metal - molecule - metal junctions. To form such junctions, molecules must be functionalised with suitable contact groups (e.g. thiols, thioethers, 4-pyridyls, amines) at each extremity. We show here that 2-(methylthio)thiophene units not only act as contact groups, but can reversibly switch between a monodentate configuration (MeS-only) and a bidentate configuration (MeS- and thienyl S) upon junction compression; as the junction is compressed the electrical conductance increases greatly with the increased molecule-contact interaction. This means that such molecules show a large-amplitude mechanical switching behavior; we also show that this is reversible and that switching can occur at a rate of at least 10 kHz. Control molecules with MeSC6H5 contact groups do not show this behavior. This, together with detailed theoretical and transport calculations on the compressed and extended molecular junctions, supports our contention that it is the thienyl S that is involved in the switching mechanism. <br /> | Nicolò Ferri; Norah Algethami; Andrea Vezzoli; Sara Sangtarash; Maeve McLaughlin; Hatef Sadeghi; Colin Lambert; Richard J. Nichols; Simon Higgins | Organic Synthesis and Reactions; Nanodevices; Theory - Computational; Interfaces; Quantum Mechanics; Surface | CC BY NC ND 4.0 | CHEMRXIV | 2018-10-31 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/60c73f36469df4b23bf42a2c/original/large-amplitude-high-frequency-single-molecule-switch.pdf |
60c7406bbdbb892e29a38182 | 10.26434/chemrxiv.7744175.v1 | Iridium-Catalyzed Silylation of C-H bonds in Unactivated Arenes: A Sterically-Encumbered Phenanthroline Ligand Accelerates Catalysis Enabling New Reactivity | We report a new system for the silylation of aryl C-H
bonds. The combination of [Ir(cod)(OMe)]<sub>2</sub> and 2,9-Me<sub>2</sub>-phenanthroline
(2,9-Me<sub>2</sub>phen) catalyzes the silylation of arenes at lower
temperatures and with faster rates than those reported previously, when the
hydrogen byproduct is removed, and with high functional group tolerance and
regioselectivity. Inhibition of reactions by the H<sub>2</sub> byproduct is
shown to limit the silylation of aryl C-H bonds in the presence of the most
active catalysts, thereby masking their high activity. Analysis of initial
rates uncovered the high reactivity of the catalyst containing the sterically hindered
2,9-Me<sub>2</sub>phen ligand but accompanying rapid inhibition by hydrogen.
With this catalyst, under a flow of nitrogen to remove hydrogen, electron-rich
arenes, including those containing sensitive functional groups, undergo
silylation in high yield for the first time, and arenes that underwent
silylation with prior catalysts react over much shorter times with lower
catalyst loadings. The synthetic value of this methodology is demonstrated by
the preparation of key intermediates in the synthesis of medicinally important
compounds in concise sequences comprising silylation and functionalization.
Mechanistic studies demonstrate that the cleavage of the aryl C-H bond is
reversible and that the higher rates observed with the 2,9-Me<sub>2</sub>phen
ligand is due to a more thermodynamically favorable oxidative addition of aryl
C-H bonds. | Caleb Karmel; Zhewei Chen; John Hartwig | Organic Compounds and Functional Groups; Organic Synthesis and Reactions; Homogeneous Catalysis | CC BY NC ND 4.0 | CHEMRXIV | 2019-02-21 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/60c7406bbdbb892e29a38182/original/iridium-catalyzed-silylation-of-c-h-bonds-in-unactivated-arenes-a-sterically-encumbered-phenanthroline-ligand-accelerates-catalysis-enabling-new-reactivity.pdf |
678a68916dde43c908f1e9b1 | 10.26434/chemrxiv-2025-2gc7v | Butyl-methylimidazolium functionalized resorcinol-formaldehyde resins: synthesis, properties, and applications to methylene blue removal | Two new imidazolium-functionalized resorcinol-formaldehyde resins RFs were synthesized, using butyl-methyl imidazolium resorcinate [C1C4Im][Res] as a new precursor or using a post-functionalization method. During its synthesis, [C1C4Im][Res] spontenaously co-crystallizes with resorcinol (in a 1 : 1 stoechiometry): the crystal structure shows H-bonds between resorcinol and resorcinate, and rarely observed π⁺-π⁻ and C-H -π interactions between imidazolium ring and resorcinate. New RFs presented substantial decreases of the band gap compared to unmodified RF (from 2.0 eV to 1.72 eV). The use of [C1C4Im][Res] significantly improves particle size uniformity compared to unmodified RF, whereas the post-functionalization method partially degrades their structure. As RF, the two new resins efficiently catalyse the photodegradation of the methylene blue cation, and the post-functionalised resin has excellent adsorption properties for this dye. | Martin Tiano; Sara Asad; Ning Zhang; Selene Charlemont; Elsa Manseur; Stéphane Daniele | Materials Chemistry | CC BY NC 4.0 | CHEMRXIV | 2025-01-23 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/678a68916dde43c908f1e9b1/original/butyl-methylimidazolium-functionalized-resorcinol-formaldehyde-resins-synthesis-properties-and-applications-to-methylene-blue-removal.pdf |
65b80b379138d23161fecb6c | 10.26434/chemrxiv-2024-mx605 | Isothiourea-Catalysed Acylative Dynamic Kinetic Resolution of Tetra-substituted Morpholinone and Benzoxazinone Lactols | The development of methods to allow the selective acylative dynamic kinetic resolution (DKR) of tetra-substituted lactols is a recognised synthetic challenge. In this manuscript, a highly enantioselective isothiourea-catalysed acylative DKR of tetra-substituted morpholinone and benzoxazinone-derived lactols is reported. The scope and limitations of this methodology have been developed, with high enantioselectivity and good to excellent yields (up to 89%, 99:1 er) observed across a broad range of substrate derivatives incorporating substitution at N(4) and C(2), di- and spirocyclic substitution at C(5)- and C(6)-position, as well as benzannulation (>35 examples in total). The DKR process is amenable to scale-up on a 1 g laboratory scale. The factors leading to high selectivity in this DKR process have been probed through computation, with an N-C=O•••isothiouronium interaction identified as key to producing ester products in highly enantioenriched form. | Haoxiang Zhu; Alejandro Manchado; Abdikani Omar Farah; Aidan McKay; David Cordes; Paul Ha-Yeon Cheong; Kevin Kasten; Andrew Smith | Theoretical and Computational Chemistry; Organic Chemistry; Catalysis; Organic Synthesis and Reactions; Stereochemistry; Organocatalysis | CC BY 4.0 | CHEMRXIV | 2024-01-31 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/65b80b379138d23161fecb6c/original/isothiourea-catalysed-acylative-dynamic-kinetic-resolution-of-tetra-substituted-morpholinone-and-benzoxazinone-lactols.pdf |
65b861cde9ebbb4db93f1996 | 10.26434/chemrxiv-2024-6tqm6 | On Validity of Constant pH Simulations | Constant pH (cpH) simulations are now a standard tool for investigating charge regulation in coarse-grained models of polyelectrolytes and colloidal systems. Originally developed for studying solutions with implicit ions, extending this method to systems with explicit ions or solvent presents several challenges. Ensuring proper charge neutrality within the simulation cell requires performing titration moves in sync with the insertion or deletion of ions -- a crucial aspect often overlooked in the literature. Contrary to prevailing views, cpH simulations are inherently grand-canonical, meaning that the controlled pH is that of the reservoir. The presence of the Donnan potential between the implicit reservoir and the simulation cell introduces significant differences between titration curves calculated for open and closed systems -- the pH of an isolated (closed) system is different from the pH of the reservoir, for the same protonation state of the polyelectrolyte. To underscore this point, in this paper we will compare the titration curves calculated using the usual cpH algorithm with those from the exact canonical simulation algorithm. In the latter case, titration moves adhere to the correct detailed balance condition, and pH is calculated using the recently introduced surface Widom insertion algorithm. Our findings reveal a very significant difference between the titration isotherms obtained using the standard cpH algorithm and the canonical titration algorithm, emphasizing the importance of using the correct simulation approach when studying charge regulation of polyelectrolyte, proteins, and colloidal particles. | Amin Bakhshandeh; Yan Levin | Physical Chemistry; Interfaces | CC BY 4.0 | CHEMRXIV | 2024-02-01 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/65b861cde9ebbb4db93f1996/original/on-validity-of-constant-p-h-simulations.pdf |
67174f7312ff75c3a12ade4e | 10.26434/chemrxiv-2024-nkkmr | Naphthalene Diimide-Embedded Donor-Acceptor Carbon Nanohoops: Photophysical, Photoconductive and Charge Transport Properties | Designing the architecture of donor−acceptor (D−A) pairs is an effective strategy to tailor the electronic structure of conjugated macrocycles for optoelectronic devices. Herein, we present the synthesis of three D−A nanohoops NDI-[n]CPP (n=7, 8, 9) containing naphthalene diimide (NDI) unit as an acceptor and [n]cycloparaphenylenes ([n]CPPs) moieties as donors. The D−A characteristics of NDI-[7~9]CPPs were substantiated through absorption and fluorescence spectroscopic studies, electrochemical investigations and computational analysis. The device investigations demonstrated that the D-A nanohoops NDI-[7~9]CPPs can serve as the photoconductive layer and demonstrate a significant generation of photocurrent with fast response upon exposure to light. The magnitude of photocurrent shows highly dependence on the size of their rings, with an increasing trendency as the ring size decreases. The generation of photocurrent in free acceptor-based CPP has rarely been reported in the previous literatures. Significantly, the C60 complexes of NDI-[7~9]CPPs exhibited a marked enhancement in photocurrent under identical conditions, in particular, the photocurrent of C60NDI-[7]CPP is ca 3.5 times greater than that of NDI-[7]CPP alone. Furthermore, the potential applications of NDI-[7~9]CPPs in electron- and hole-transport devices have been also explored, revealing the clear evidence of their bipolar behavior as an active charge transport layer. | Shengzhu Guo; Lin Liu; Linshan Liu; Yanqing Fan; Huiji Yang; Jing He; Ying Wang; Zhishan Bo; Xuebo Chen; Xinjun Xu; Hua Jiang | Organic Chemistry; Supramolecular Chemistry (Org.) | CC BY NC ND 4.0 | CHEMRXIV | 2024-10-23 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/67174f7312ff75c3a12ade4e/original/naphthalene-diimide-embedded-donor-acceptor-carbon-nanohoops-photophysical-photoconductive-and-charge-transport-properties.pdf |
677db89b6dde43c908aa23ed | 10.26434/chemrxiv-2025-5zs9m | Catechol chemistry unleashed: Spontaneous reactions in physiologically-relevant media | Catecholic compounds, characterized by their distinct dihydroxybenzene functional groups, are recognized for their diverse biological roles and emerging therapeutic potential. Despite significant advances in understanding their biotransformation and chemical reactivity, the potential for enzyme-independent reactions of catechols under physiologically relevant conditions remains underexplored. This study investigates the enzyme- and cell-free transformations of catechol in cell culture media and biocompatible buffers. In neutral to mildly alkaline (pH 7.0-8.0) phosphate buffer without additional additives, catechol transformed into dark-coloured, spectrally active species (“browning”) within 6 hours, in a temperature-dependent manner. The presence of amine-containing molecules – including amino acids (glycine, lysine, proline), biocompatible buffers (tris(hydroxymethyl)aminomethane, or Tris), and proteins (bovine serum albumin, or BSA) – dramatically accelerated browning rates in a pH-dependent manner, with visually detectable and spectrophotometrically quantifiable changes occurring within minutes. BSA-enhanced catechol browning also altered the protein's electrophoretic mobility, suggesting structural modifications induced by the browning reaction. These transformations may occur before cellular uptake or interaction with biological targets, potentially influencing the bioavailability and therapeutic efficacy of catecholic compounds. This work raises new questions about the structural-functional relationships of catecholic compounds and underscores the importance of accounting for their spontaneous reactivity in experimental design. | Christopher Dieni; Brett Spiess | Biological and Medicinal Chemistry; Biochemistry; Chemical Biology; Drug Discovery and Drug Delivery Systems | CC BY 4.0 | CHEMRXIV | 2025-01-09 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/677db89b6dde43c908aa23ed/original/catechol-chemistry-unleashed-spontaneous-reactions-in-physiologically-relevant-media.pdf |
67ac411f6dde43c908870384 | 10.26434/chemrxiv-2025-m8262 | DNA-Drug Conjugates (DDCs) for computed delivery | Antibody-drug conjugates (ADCs) offer the potential to deliver potent cytotoxics with unprecedented specificity with respect to a given biomarker. In parallel, development in DNA circuitry and DNA-protein conjugates provide opportunities to design systems that integrate inputs and compute outputs with the potential of amplified responses through hybridization chain reactions (HCRs). Herein, we report a system based on affinity miniproteins (affibodies)-DNA conjugates and aptamer-DNA conjugates to target specific cells via biomarker recognition, yielding a logic-gated response. We demonstrate that this system can be used to trigger HCRs conditionally either on the presence of two biomarkers or based on the density of a single biomarker. Additionally, we show that receptor-mediated uptake of the HCR-generated assemblies can be used to release a combination of payloads. This mechanism successfully achieves the targeted delivery of payloads through a cleavable linker in DNA-Drug conjugates (DDCs), in analogy to ADCs with an added amplification reaching above 100-fold. Crucially, we find that the nature of the drug in DDC is critical for the efficiency of this delivery and that a combination of drugs can be administered simultaneously. Finally, we show that biomarker-triggered HCRs can also be used to recruit generic antibodies. | Si-Kai Chen; Miguel LopezTena; Francesco Russo; Emma E. watson; Millicent Dockerill; Javier Cabellogarcia; Sofia Barluenga; Nicolas Winssinger | Biological and Medicinal Chemistry; Chemical Biology; Drug Discovery and Drug Delivery Systems | CC BY NC ND 4.0 | CHEMRXIV | 2025-02-14 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/67ac411f6dde43c908870384/original/dna-drug-conjugates-dd-cs-for-computed-delivery.pdf |
66ba1c3dc9c6a5c07a0106da | 10.26434/chemrxiv-2024-vcqgp | Homologous Lanthanide Nickel Silicides Based on Oligomeric Triangular Blocks: Crystal Structures and Physical Properties | Isostructural series of homologous silicides Lnn(n+1)+xNin(n+5)+ySi(n+1)(n+2)-z (n = 4–6) have been obtained with Ln = Ce, Pr and Gd at 1000 C. All of them crystallize in the hexagonal space group type P63/m, exhibit short unit cell c parameters and variable but strongly correlating a parameters (n = 4: a = 20.795–20.826(9), c = 3.994–4.041(1) Å; n = 5: a = 24.693–24.726(4), c = 4.000–4.066(1) Å, and n = 6: a = 28.716–28.760(1), c = 3.9983–4.0734(3) Å). The crystal structures are represented by fused oligomeric SrPtSb -type blocks – La-centered Ni6Si6 hexagonal prisms forming equilateral domains with the edge size equal to n. The polyanionic triangular motifs and the cationic components alternate along all crystallographic axes. The newly discovered compounds Lnn(n+1)+xNin(n+5)+ySi(n+1)(n+2)-z represent asymmetric higher-n Ni-rich compositional and structural mirrors to the rare reported Ln-rich representatives Ln(n+1)(n+2)Nin(n-1)+2Sin(n+1). Unit cell parameter trends and magnetic measurements suggest the intermediate valence character of the Ce atoms. | Davide Grilli; Volodymyr Smetana; Vitalii Shtender; Sheikh Jamil Ahmed; Marcella Pani; Pietro Manfrinetti; Anja-Verena Mudring | Physical Chemistry; Materials Science; Inorganic Chemistry; Alloys; Lanthanides and Actinides; Crystallography | CC BY 4.0 | CHEMRXIV | 2024-08-13 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/66ba1c3dc9c6a5c07a0106da/original/homologous-lanthanide-nickel-silicides-based-on-oligomeric-triangular-blocks-crystal-structures-and-physical-properties.pdf |
60c74f55f96a00358e287c11 | 10.26434/chemrxiv.12894818.v1 | The tmQM Dataset - Quantum Geometries and Properties of 86k Transition Metal Complexes | <div>We report the transition metal quantum mechanics dataset (tmQM), which contains the geometries and properties of a large transition metal-organic compound space. tmQM is comprised of 86,665 mononuclear complexes extracted from the Cambridge Structural Database, including Werner, bioinorganic and organometallic complexes based on a large variety of organic ligands and 30 transition metals (the 3d, 4d and 5d from groups 3 to 12). All complexes are closed-shell, and with a formal charge in the range {+1, 0, -1}e. The tmQM dataset provides the Cartesian coordinates of all metal complexes optimized at the DFTB(GFN2-xTB) level, and their molecular size, stoichiometry, and metal node degree. The quantum properties were computed at the DFT(TPSSh-D3BJ/def2-SVP) level, and include the electronic and dispersion energies, HOMO and LUMO orbital energies, HOMO-LUMO gap, dipole moment, and natural charge of the metal center; DFTB(GFN2-xTB) polarizabilities are also provided. Pairwise representations showed the low correlation between these properties, providing nearly continuous maps with unusual regions of the chemical space; e.g. complexes combining large polarizabilities with wide HOMO-LUMO gaps, and complexes combining low-energy HOMO orbitals with electron-rich metal centers. The</div><div>tmQM dataset can be exploited in the data-driven discovery of new metal complexes, including predictive models based on machine learning. These models may have a strong impact on the fields in which transition metal chemistry plays a key role; e.g. catalysis, organic synthesis, and materials science. tmQM is an open dataset that can be downloaded free of charge from https://github.com/bbskjelstad/tmqm</div> | David Balcells; Bastian Bjerkem Skjelstad | Computational Chemistry and Modeling; Machine Learning; Chemoinformatics - Computational Chemistry; Theory - Organometallic; Transition Metal Complexes (Organomet.) | CC BY NC ND 4.0 | CHEMRXIV | 2020-08-31 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/60c74f55f96a00358e287c11/original/the-tm-qm-dataset-quantum-geometries-and-properties-of-86k-transition-metal-complexes.pdf |
65e0717166c1381729d75bff | 10.26434/chemrxiv-2024-t6shw | Penta fever going on: conductive Penta-BCN4 with negative differential resistance (NDR) | Pentagonal 2D structures, surpassing conventional hexagonal sheets, are gaining increasing attention due to their exceptional properties and diverse applications. In this study, we investigate penta-BCN4, a ternary monolayer 2D penta structure with intrinsically exceptional properties. Using Density Functional Theory calculations, we found that penta-BCN4 is a conductive material with mechanical, thermal, and dynamic stability. Penta-BCN4 exhibits a high Young’s modulus and a small Poisson ratio, which are isotropic in different directions. In contrast, penta-BCN, which has been previously studied, is mechanically anisotropic. We also discovered that one of the most intriguing properties of penta-BCN4's band structure is the phenomenon of negative differential resistance (NDR). To assess NDR more precisely, we computed the transport in the direction of the N-N bond in addition to the throughput in the direction of the lattice vector (a). The intrinsic NDR of the penta-BCN4 monolayer, combined with its vanishing band gap, makes this material appealing for technological applications, as B, C, and N are abundant resources, light in mass, and environmentally safe. This research expands the possibilities of monolayer 2D penta structures into new avenues. | Mahdi Faghihnasiri; Aidin Ahmadi; Hatef Yousefi-Mashhour; Safwat Abdel-Azeim ; Oliver Kühn; Mohamed Shibl | Theoretical and Computational Chemistry | CC BY NC 4.0 | CHEMRXIV | 2024-03-01 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/65e0717166c1381729d75bff/original/penta-fever-going-on-conductive-penta-bcn4-with-negative-differential-resistance-ndr.pdf |
67617560fa469535b9e5c415 | 10.26434/chemrxiv-2024-nkqt1 | Terpene-derived polyester-block-polycarbonates using metal-free catalysis | Sustainable materials are a large research focus due to depleting resources and increasing environmental pollution. Therefore, bio-derived building blocks from renewable feedstocks are being pursued as an alternative to fossil-derivatives for producing polymers. Here, we have prepared a series of polyester and polyester-block-polycarbonate copolymers from a metal-free ring-opening copolymerization (ROCOP) of various terpene-derived cyclic anhydrides, epoxides (cyclohexene oxide (CHO) and propylene oxide (PO)), and carbon dioxide (CO2) under neat (solvent-free) conditions. Cyclic anhydrides were prepared via microwave-assisted Diels Alder reactions between terpenes and maleic anhydride (up to 90% yield). The ROCOP catalyst system consisted of triphenylborane (BPh3) with bis(triphenylphosphine)iminium chloride (PPNCl) and, after complete conversion of anhydride, resulted in polymers with moderate molecular weights (Mn up to 21 kDa), and good dispersities (between 1.05 and 1.75). Thermal analysis resulted in a single glass transition temperature (between 1.5 C and 101 C) indicating amorphic materials. 13C{1H} NMR spectroscopy revealed high stereoregularity with respect to substituent methyl groups and di-ester units and 2D DOSY NMR spectroscopy confirmed a single polymer chain was formed by sequential copolymerizations. Residual olefinic groups in the polymer backbone provides opportunity for post-polymerization functionalization and, therefore, further tailoring of macroscopic properties. | Mikhailey Wheeler; Allison Clark; Andrew Kinsman; Francesca Kerton | Inorganic Chemistry; Catalysis; Polymer Science; Polymerization (Polymers); Polymers; Homogeneous Catalysis | CC BY NC 4.0 | CHEMRXIV | 2024-12-20 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/67617560fa469535b9e5c415/original/terpene-derived-polyester-block-polycarbonates-using-metal-free-catalysis.pdf |
6196edc4b039f22340aa5bb7 | 10.26434/chemrxiv-2021-32gxb | Quasi-Relativistic Calculation of EPR g-Tensors with Derivatives of the Decoupling Transformation, Gauge-Including Atomic Orbitals, and Magnetic Balance | We present an exact two-component (X2C) ansatz for the EPR g-tensor using gauge-including atomic orbitals (GIAOs) and a magnetically balanced basis set expansion. In contrast to previous X2C and "fully" relativistic ansätze for the g-tensor, this implementation results in a gauge-origin invariant formalism. Furthermore, the derivatives of the relativistic decoupling matrix are considered to form the complete analytical derivative of the X2C Hamiltonian.
To reduce the associated computational costs, we apply the diagonal local approximation to the unitary decoupling transformation (DLU) and the (multipole-accelerated) resolution of the identity approximation. The X2C ansatz is compared to Douglas-Kroll-Hess theory and the zeroth-order regular approximation for 11 diatomic molecules. The impact of the relativistic Hamiltonian, the basis set, and the density functional approximation is subsequently assessed for a set of 17 transition-metal complexes to complement our previous work on the hyperfine coupling constant [DOI: 10.33774/chemrxiv-2021-wnz1v-v2]. In total, 24 basis sets and 22 density functional approximations are considered.
The quasi-relativistic X2C and DLU-X2C Hamiltonians accurately reproduce the results of the parent "fully"
relativistic four-component theory when accounting for two-electron picture-change effects with the modified screened nuclear spin-orbit approximation in the respective
one-electron integrals and integral derivatives. Generally, the uncontracted Dyall and segmented-contracted Karlsruhe x2c-type basis sets perform well when compared to large even-tempered basis sets. Moreover, (range-separated) hybrid density functional approximations are needed to match the experimental findings. Here, hybrids based on
the meta -generalized gradient approximation are not an
a priori improvement. Compared to the other computational parameters, the impact of the GIAOs and the magnetic balance on the actual results in standard calculations is less pronounced. Routine calculations of large molecules are possible with widely available and comparably low-
cost hardware as demonstrated for [Pt(C6Cl5)4]− with 3360 basis functions and three spin-(1/2) La(II) and Lu(II) compounds. Both approaches based on a common gauge
origin and GIAOs using triple- ζ basis sets lead to a good agreement with the experimental findings. The best agreement is found with hybrid functionals such as PBE0 and ωB97X-D. | Yannick J. Franzke; Jason M. Yu | Theoretical and Computational Chemistry; Physical Chemistry; Organometallic Chemistry; Theory - Computational; Quantum Mechanics; Spectroscopy (Physical Chem.) | CC BY NC ND 4.0 | CHEMRXIV | 2021-11-22 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/6196edc4b039f22340aa5bb7/original/quasi-relativistic-calculation-of-epr-g-tensors-with-derivatives-of-the-decoupling-transformation-gauge-including-atomic-orbitals-and-magnetic-balance.pdf |
618104a5ad7f7ccaf151f5c1 | 10.26434/chemrxiv-2021-c19nw | Phosphorescence Enables Identification of Electronic State for Acridinium Salt in Solutions | Understanding intermolecular interactions between Lewis acid and base pairs is of fundamental importance in predicting non-covalent bonding and chemical reactivity. Here we show that an acridinium derivative, a Lewis acid, exhibits various degrees of interactions with Lewis bases of increasing nucleophilicity, including water (HOH), methanol (CH3OH), tetrahydrofuran (ROR), amines (R3N) and t-butoxide (RO-). Each interaction appears to result in a different type of solution state: solvation (e.g., water), coordination (e.g., tetrahydrofuran), chemical bonding (e.g., triethylamine), and radicals (e.g., t-butoxide). The solvated and coordinated acridinium molecules exhibit almost identical 1H-NMR spectra, but possess drastically different UV absorption and luminescence emission, particularly phosphorescence; on the other hand, coordinated and chemically bonded acridinium species which are differentiated by heat calorimetry titration, share the same luminescence spectra but show two different sets of 1H-NMR peaks. These distinct solution states could only be revealed by a combination of NMR and molecular fluorescence/phosphorescence spectroscopic methods, which could provide important clues in the mechanistic understanding of many important processes such as photo-redox reactions. The current report serves as an example of using phosphorescence spectroscopy as a complementary tool for characterizing electronic structures for interaction between organic molecules. | Xiaolong Zhang; Jiajun Du; Fan Liao; Hao Su; Xuepeng Zhang ; Guoqing Zhang | Physical Chemistry; Physical and Chemical Properties | CC BY 4.0 | CHEMRXIV | 2021-11-03 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/618104a5ad7f7ccaf151f5c1/original/phosphorescence-enables-identification-of-electronic-state-for-acridinium-salt-in-solutions.pdf |
64d8881869bfb8925ada9909 | 10.26434/chemrxiv-2023-n7xbt-v2 | A larger basis set describes atomization energy core-valence correction better than a higher-order coupled-cluster method | The accuracy of coupled-cluster methods for the computation of core-valence correction to atomization energy was assessed. Truncation levels up to CCSDTQP were considered together with (aug-)cc-pwCVnZ (n = D, T, Q, 5) basis sets and three different extrapolation techniques (canonical and flexible Helgaker formula and Riemann zeta function extrapolation). With the exception of CCSD, a more accurate correction can be obtained from a larger basis set with a lower-level coupled-cluster method, and not vice versa. For the CCSD(T) level, it also implies faster computations with modern codes. We also discussed the importance of moving to higher-order or all-electron methods for geometry optimizations. The present study provides the general knowledge needed for the most accurate state-of-the-art computations. | Aleksandr Chamkin; Elena Chamkina | Theoretical and Computational Chemistry; Computational Chemistry and Modeling; Theory - Computational | CC BY NC ND 4.0 | CHEMRXIV | 2023-08-14 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/64d8881869bfb8925ada9909/original/a-larger-basis-set-describes-atomization-energy-core-valence-correction-better-than-a-higher-order-coupled-cluster-method.pdf |
60c7426ef96a0046de2865fc | 10.26434/chemrxiv.8230427.v2 | Improved Sampling in Ab Initio-Based Free Energy Calculations of Amino Acids at Solid-Liquid Interfaces: A Tight-Binding Assessment on TiO2 Anatase (101) | Atomistic simulations are powerful for probing molecules at bioinorganic interfaces and excellent complements to scarcely available experimental techniques. The free energy controls the adsorption behavior of molecules on nanosurfaces, and is therefore a quantity of particular importance. Advanced sampling techniques can efficiently explore the adsorption free energy landscape, but molecular simulations with classical (Newtownian) dynamics fail to capture charge transfer and polarization at the solid-liquid interface. First principle simulations do not suffer from this limitation but come with a heavy computational load. Here, we introduce an efficient protocol to explore the free energy of adsorption in the ab initio framework. This approach accurately models the complex phenomena at bio-inorganic surfaces on the nanoscale and properly samples the relevant thermodynamic properties. We present a case study of adsorption of the Lysine and Aspartate amino acids on the anatase (101) TiO<sub>2</sub> surface with the tight binding method. The high values of the calculated adsorption free energies highlight the importance of a proper description of the electronic state for surface binding processes. | Lorenzo Agosta; Erik G. Brandt; Alexander Lyubartsev | Bioinorganic Chemistry; Computational Chemistry and Modeling; Theory - Computational; Interfaces | CC BY NC ND 4.0 | CHEMRXIV | 2019-06-07 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/60c7426ef96a0046de2865fc/original/improved-sampling-in-ab-initio-based-free-energy-calculations-of-amino-acids-at-solid-liquid-interfaces-a-tight-binding-assessment-on-ti-o2-anatase-101.pdf |
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