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60c75516702a9bfc3618c61b | 10.26434/chemrxiv.14039738.v1 | A Method for the Growth of Uniform Silica Shells on Different Size and Morphology Upconversion Nanoparticles | Lanthanide-doped upconversion nanoparticles have emerged as attractive candidates for biomedical applications. This is due to their excitation and emission wavelengths, which lay the foundation for deeper penetration depth into biological tissue, higher resolution due to reduced scattering and improved imaging contrast as a result of a decrease in autofluorescence background. Usually, their encapsulation within a biocompatible silica shell is a requirement for their dispersion within complex media or for further functionalization of the upconversion nanoparticle surface. However, the creation of a silica shell around upconversion nanoparticles can be often challenging, many times resulting in partial silica coating or nanoparticle aggregation, as well as the production of a large number of silica particles as a side product. In this work we demonstrate a method to accurately predict the experimental conditions required to form a high yield of silica-coated upconversion nanoparticles, regardless of their shape and size. | Elena Ureña-Horno; Maria Eleni Kyriazi; Antonios Kanaras | Nanostructured Materials - Nanoscience | CC BY NC ND 4.0 | CHEMRXIV | 2021-02-17 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/60c75516702a9bfc3618c61b/original/a-method-for-the-growth-of-uniform-silica-shells-on-different-size-and-morphology-upconversion-nanoparticles.pdf |
632daf2dcf38293d96af670d | 10.26434/chemrxiv-2022-hngnn | The structure of a pentachromium(II) extended metal atom chain at 3 K: Cotton’s conjecture proven
| We provide definitive experimental proof that prototypical string-like compound [Cr5(tpda)4(NCS)2] has alternating long and short Cr-Cr separations in the solid state, as conjectured by F. A. Cotton, rather than essentially equally spaced Cr atoms, as initially claimed (H2tpda = N2,N6-di(pyridin-2-yl)pyridine-2,6-diamine). Single-crystal X-ray data collected from 292 to 3 K revealed that the misinterpretation is caused by pseudo-merohedral twinning and that bond length alternation is enhanced at low temperature. | Andrea Cornia; Alessio Nicolini; Charles J. McMonagle; Michael R. Probert | Inorganic Chemistry; Coordination Chemistry (Inorg.); Crystallography – Inorganic | CC BY NC 4.0 | CHEMRXIV | 2022-09-26 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/632daf2dcf38293d96af670d/original/the-structure-of-a-pentachromium-ii-extended-metal-atom-chain-at-3-k-cotton-s-conjecture-proven.pdf |
618115d98ac7a284c364f8ef | 10.26434/chemrxiv-2021-v7v6g | Naive Bayes classification model for isotopologue
detection in LC-HRMS data | Isotopologue identification or removal is a necessary step to reduce the number of features that need to be identified in samples analyzed with non-targeted analysis. Currently available approaches rely on either predicted isotopic patterns or an arbitrary mass tolerance, requiring information on the molecular formula or instrumental error, respectively. Therefore, a Naive Bayes isotopologue classification model was developed that does not depend on any thresholds or molecular formula information. This classification model uses elemental mass defects of six elemental ratios and can successfully identify isotopologues in both theoretical isotopic patterns and wastewater influent samples, outperforming one of the most commonly used approaches (i.e., 1.0033 Da mass difference method - CAMERA). | Denice van Herwerden; Jake O'Brien ; Phil Choi; Kevin Thomas; Peter Schoenmakers; Saer Samanipour | Analytical Chemistry; Earth, Space, and Environmental Chemistry; Chemoinformatics; Environmental Analysis; Mass Spectrometry | CC BY 4.0 | CHEMRXIV | 2021-11-03 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/618115d98ac7a284c364f8ef/original/naive-bayes-classification-model-for-isotopologue-detection-in-lc-hrms-data.pdf |
60c746c2842e65b988db2886 | 10.26434/chemrxiv.11400405.v1 | Intrinsic Stacking Interactions of Natural and Artificial Nucleobases | The intrinsic (gas-phase) stacking energies of natural and artificial nucleobases were explored using density functional theory (DFT) and correlated ab initio methods. Ranking the stacking strength of natural nucleobase dimers revealed a preference in binding partner similar to that seen from experiments, namely G > C > A > T > U. Decomposition of these interaction energies using symmetry-adapted perturbation theory (SAPT) showed that these dispersion dominated interactions are modulated by electrostatics. Artificial nucleobases showed a similar stacking preference for natural nucleobases and were also modulated by electrostatic interactions. A robust predictive multivariate model was developed that quantitively predicts the maximum stacking interaction between natural and a wide range of artificial nucleobases using molecular descriptors based on computed electrostatic potentials (ESPs) and the number of heavy atoms. This model should find utility in designing artificial nucleobase analogs that exhibit stacking interactions comparable to those of natural nucleobases. Further analysis of the descriptors in this model unveil the origin of superior stacking abilities of certain nucleobases, including cytosine and guanine. | Drew P. Harding; Laura J. Kingsley; Glen Spraggon; Steven Wheeler | Computational Chemistry and Modeling | CC BY NC ND 4.0 | CHEMRXIV | 2019-12-23 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/60c746c2842e65b988db2886/original/intrinsic-stacking-interactions-of-natural-and-artificial-nucleobases.pdf |
60c73d93842e654937db17c9 | 10.26434/chemrxiv.5950327.v1 | Remarkable Sensing Behavior of Pyrazole-based Chemosensor Towards Cu(II) Ion Detection: Synthesis, Characterization and Theoretical Investigations | We report the synthesis of a new imine based
ligand, 3-((3-methoxybenzylidene)amino)-1H-pyrazol-5-ol (<b>HL</b>) and its Cu(II) complexes in 2:1 (<b>HL</b>:metal) and 1:1:1 (<b>HL</b>:metal:<b>HQ</b>) stoichiometric ratio using
8-hyroxyquinoline (<b>HQ</b>) as an
additional bidentate ligand. The synthesized ligand (<b>HL</b>) and its Cu(II) complexes (<b>1</b>
and <b>2</b>) are structurally
characterized using FT-IR, electronic absorption and emission, NMR, MS and TGA
techniques. Furthermore, the complexation of Cu<sup>2+</sup> with <b>HL</b> leads to the immediate formation of
brown colored solution which indicates that <b>HL</b> can act as simple colorimetric sensor for Cu<sup>2+ </sup>ions.
We further investigated that the sensor could selectively bind to the Cu<sup>2+
</sup>ions even in the presence of competitive ions such as Mn<sup>2+</sup>, Fe<sup>2+</sup>,
Co<sup>2+</sup>, Ni<sup>2+</sup>, Zn<sup>2+</sup>, Ag<sup>+</sup> and Na<sup>+ </sup>ions
in aqueous solutions which was studied by electronic absorption spectroscopy.
The <b>HL</b> ligand and corresponding
Cu(II) complexes have been investigated for their reactive properties by
density functional theory (DFT) calculations. Quantum molecular descriptors
describing local reactive properties have been calculated in order to identify
the most reactive molecule sites of title compounds. DFT calculations
encompassed <a></a><a></a><a>molecular electrostatic potential (MEP), local average ionization
energies (ALIE), Fukui functions and bond dissociation energies for hydrogen
abstraction (H-BDE)</a>. | Nagaraj Nayak; Shiva Prasad Kollur; Renjith Raveendran Pillai; Stevan Armaković; Sanja J. Armaković | Coordination Chemistry (Inorg.); Ligands (Inorg.); Spectroscopy (Inorg.); Theory - Inorganic; Theory - Computational | CC BY NC ND 4.0 | CHEMRXIV | 2018-03-06 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/60c73d93842e654937db17c9/original/remarkable-sensing-behavior-of-pyrazole-based-chemosensor-towards-cu-ii-ion-detection-synthesis-characterization-and-theoretical-investigations.pdf |
6719ed0b98c8527d9e2a8bd2 | 10.26434/chemrxiv-2024-s6gmv | Photocatalytic Multiple Deuteration of Polyethylene Glycol Derivatives using Deuterium Oxide | Deuterated molecules are of growing interest because of the specific characteristics of deuterium, such as stronger C–D bonds being stronger than C–H bonds. Polyethylene glycols (PEGs) are widely utilized in scientific fields (e.g., drug discovery and material sciences) as linkers and for the improvement of various properties (solubility in water, stability, etc.) of mother compounds. Therefore, deuterated PEGs can be used as novel tools for drug discovery. Although the H/D exchange reaction (deuteration) is a powerful and straightforward method to produce deuterated compounds, the deuteration of PEGs bearing many unactivated C(sp3)–H bonds has not been developed. Herein, we report the photocatalytic deuteration of multiple PEGs using tetra-n-butylammonium decatungstate (TBADT) and D2O as inexpensive deuterium sources. This deuteration can be adapted to PEG derivatives bearing various substituents ((hetero)aryl, benzoyl, alkyl, etc.) at the terminal oxygen atoms of PEGs. The deuteration efficiencies of the alpha-oxy C(sp3)–H bonds at the terminal positions of the PEGs were strongly influenced by the substituents. These reactivities were elucidated by density functional theory calculations of the reaction barriers towards the formation of radical intermediates, induced by the excited state of TBADT and the PEG substrate. In addition, the applicability of deuterated PEGs to internal standard experiments and Raman spectroscopy was demonstrated. | Riku Ogasahara; Miyu Mae; Keisuke Matsuura; Sota Yoshimura; Takayoshi Ishimoto; Taro Udagawa; Kazuo Harada; Hiroyoshi Fujioka; Mako Kamiya; Rio Asada; Hiromasa Uchiyama; Yuichi Tozuka; Shuji Akai; Yoshinari Sawama | Organic Chemistry; Catalysis | CC BY NC ND 4.0 | CHEMRXIV | 2024-10-25 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/6719ed0b98c8527d9e2a8bd2/original/photocatalytic-multiple-deuteration-of-polyethylene-glycol-derivatives-using-deuterium-oxide.pdf |
60c7428f567dfe1a9cec3f67 | 10.26434/chemrxiv.8304524.v1 | Investigating the Mechanism of Post-Treatment on PEDOT:PSS via Single-Particle Absorption Spectroscopy | The conductive polymer PEDOT:PSS, widely used in optoelectronic devices, exhibits improved conductivity upon post-treatment, but the mechanism of this improvement is difficult to fully ascertain. The effects of thermal annealing and DMSO post-treatment on PEDOT:PSS, from the nano- to mesoscale, are studied using single-particle absorption spectroscopy. An average decrease in size and apparent increase in rotational order of individual particles are observed with both treatments, including unexpected correlations between change in rotational order and initial properties. Simulation of these transformations and correlations occurring during the annealing process reveal that the effects of DMSO-post treatment can be explained by oligomer depletion and do not explicitly require conformational changes including oligomer rotation. | Morgan Rea; Feng Pan; Erik Horak; Kassandra Knapper; Hoang Nguyen; Cecilia Vollbrecht; Randall Goldsmith | Polymers; Spectroscopy (Physical Chem.) | CC BY NC ND 4.0 | CHEMRXIV | 2019-06-24 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/60c7428f567dfe1a9cec3f67/original/investigating-the-mechanism-of-post-treatment-on-pedot-pss-via-single-particle-absorption-spectroscopy.pdf |
60c74da9337d6c77b7e27e16 | 10.26434/chemrxiv.12647033.v1 | Critical Benchmarking of the G4(MP2) Model, the Correlation Consistent Composite Approach and Popular Density Functional Approximations on a Probabilistically Pruned Benchmark Dataset of Formation Enthalpies | First-principles calculation of the standard formation enthalpy, $\Delta H_f^0$~(298K), in such large scale as required by chemical space explorations, is amenable only with density functional approximations (DFAs) and some composite wave function theories (cWFTs). Alas, the accuracies of popular range-separated hybrid, `rung-4' DFAs, and cWFTs that offer the best accuracy-vs.-cost trade-off have as yet been established only for datasets predominantly comprising small molecules, hence, their transferability to larger datasets remains vague. In this study, we present an extended benchmark dataset of over two-thousand values of $\Delta H_f^0$ for structurally and electronically diverse molecules. We apply quartile-ranking based on boundary-corrected kernel density estimation to filter outliers and arrive at Probabilistically Pruned Enthalpies of 1908 compounds (PPE1908). For this dataset, we rank the prediction accuracies of G4(MP2), ccCA and 23 popular DFAs using conventional and probabilistic error metrics. We discuss systematic prediction errors and highlight the role an empirical higher-level correction (HLC) plays in the G4(MP2) model. Furthermore, we comment on uncertainties associated with the reference empirical data for atoms and systematic errors introduced by these that grow with the molecular size. We believe these findings to aid in identifying meaningful application domains for quantum thermochemical methods. | sambit kumar das; Sabyasachi Chakraborty; Raghunathan Ramakrishnan | Theory - Computational | CC BY NC ND 4.0 | CHEMRXIV | 2020-07-14 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/60c74da9337d6c77b7e27e16/original/critical-benchmarking-of-the-g4-mp2-model-the-correlation-consistent-composite-approach-and-popular-density-functional-approximations-on-a-probabilistically-pruned-benchmark-dataset-of-formation-enthalpies.pdf |
6456df3007c3f0293753c26c | 10.26434/chemrxiv-2023-f5gck | Low-Temperature, Single-Source, Chemical Vapor Deposition of Molybdenum Nitride Thin Films | The 1,4-di-tert-butyl-1,3-diazabutadiene adduct of bis(tert-butylimido)dichloro-molybdenum(VI), (tBuN)2MoCl2·dad, was used as a single-source precursor for the chemical vapor deposition of molybdenum nitride from 350 – 600ºC. Deposition at 400 ºC had a growth rate of 55 nm·h−1 and was comprised of a mixture of Mo2N and MoN, based on X-ray photoelectron spectroscopy and grazing-incidence X-ray diffraction results. The films are essentially featureless and are as smooth as the underlying substrate, based on atomic force microscopy measurements. Because the depositions could be carried out at a low temperature there was minimal carbon (1.4%) inclusion in the film as shown by XPS. | Michael Land; Justin Lomax; Sean Barry | Inorganic Chemistry; Coordination Chemistry (Inorg.); Transition Metal Complexes (Inorg.); Materials Chemistry | CC BY NC ND 4.0 | CHEMRXIV | 2023-05-08 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/6456df3007c3f0293753c26c/original/low-temperature-single-source-chemical-vapor-deposition-of-molybdenum-nitride-thin-films.pdf |
6294899fd50adf0bd5e45fa7 | 10.26434/chemrxiv-2021-39nhv-v3 | A thermalized electrokinetics model including stochastic
reactions suitable for multiscale simulations of reaction-advection-diffusion systems | We introduce a scheme to simulate the spatial and temporal evolution of the densities of charged species, taking into account diffusion, thermal fluctuations, coupling to a carrier fluid, and chemical reactions. To this end, the diffusive fluxes in the electrokinetic model by Capuani et al. [1] are supplemented with thermal fluctuations. Chemical reactions are included via an additional source term in the mass balance equation. The diffusion-reaction model is then coupled to a solver for fluctuating hydrodynamics based on the lattice Boltzmann method. This combination is particularly useful for soft matter simulations, due to the ability to couple particles to the lattice-Boltzmann fluid. These could, e.g., be charged colloids or polymers, which then interact with an ion distribution. We describe one implementations based on the automatic code generation tools pystencils and lbmpy, and another one that is contained in the molecular dynamics package ESPResSo and that allows for an easy coupling of particles to the density fields. We validate our implementations by comparing to several known analytic results. Our method can be applied to coarse-grained catalysis problems as well as to many other multi-scale problems that require the coupling of explicit-particle simulations to flow fields, diffusion, and reaction problems in arbitrary geometries. | Ingo Tischler; Florian Weik; Robert Kaufmann; Michael Kuron; Rudolf Weeber; Christian Holm | Theoretical and Computational Chemistry; Physical Chemistry; Theory - Computational; Transport phenomena (Physical Chem.) | CC BY NC 4.0 | CHEMRXIV | 2022-05-30 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/6294899fd50adf0bd5e45fa7/original/a-thermalized-electrokinetics-model-including-stochastic-reactions-suitable-for-multiscale-simulations-of-reaction-advection-diffusion-systems.pdf |
60c74477702a9b78d018a842 | 10.26434/chemrxiv.9808391.v1 | Water in Hydration Shell of an Azide Ion: Structure and Dynamics of Solute-water Hydrogen Bonds and Vibrational Spectral Diffusion from First Principles Simulations At Supercritical Condition | <p>A series of ab initio MD simulations has been carried out for aqueous azide (N<sub>3</sub><sup>-</sup>) ion solutions at three different densities and at supercritical condition (673 K) using Car-Parrinello molecular dynamics simulation. The time dependent trajectories at three different densities have been used to analyze the hydrogen bond dynamics, residence dynamics, dangling OD bond dynamics and spectral diffusion and underlying connections between them. The time dependent frequency of both the OD and NN stretching mode has been calculated using the time series analysis of the wavelet method. The population correlation function approach has been used to compute the hydrogen bond dynamics, dangling OD bond and residence dynamics of the Sc-water both inside and outside the solvation shell of the ion. The faster hydrogen bond dynamics has been observed in the vicinity of the azide ion, however the calculated OD stretching frequency is found to show red shift in the vicinity of the azide ion indicative to the formation of stronger ion-water hydrogen bond even at the supercritical condition. The overall hydrogen bond dynamics at the supercritical condition was faster with respect to the aqueous azide ion solutions at the ambient condition.</p> | Anwesa Karmakar | Theory - Computational | CC BY NC ND 4.0 | CHEMRXIV | 2019-09-13 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/60c74477702a9b78d018a842/original/water-in-hydration-shell-of-an-azide-ion-structure-and-dynamics-of-solute-water-hydrogen-bonds-and-vibrational-spectral-diffusion-from-first-principles-simulations-at-supercritical-condition.pdf |
60c759bc567dfe0b20ec6abb | 10.26434/chemrxiv.13653203.v2 | Validating the CHARMM36m Protein Force Field with LJ-PME Reveals Altered Hydrogen Bonding Dynamics under Elevated Pressures | <p>The pressure-temperature phase diagram is important to our understanding of the physics of biomolecules. Compared to studies on temperature effects, studies of the pressure dependence of protein dynamic are rather limited. Molecular dynamics (MD) simulations with fine-tuned force fields (FFs) offer a powerful tool to explore the influence of thermodynamic conditions on proteins. Here we evaluate the transferability of the CHARMM36m (C36m) protein force field at varied pressures compared with NMR data using ubiquitin as a model protein. The pressure dependences of J couplings for hydrogen bonds and order parameters for internal motion are in good agreement with experiment. We demonstrate that the C36m FF combined with the LJ-PME method is suitable for simulations in a wide range of temperature and pressure. As the ubiquitin remains stable up to 2500 bar, we identify the mobility and stability of different hydrogen bonds in response to pressure. Based on those results, C36m is expected to be applied to more proteins in the future to further investigate protein dynamics under elevated pressures.</p> | You Xu; Jing Huang | Bioinformatics and Computational Biology; Biophysics; Computational Chemistry and Modeling; Theory - Computational | CC BY NC ND 4.0 | CHEMRXIV | 2021-06-01 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/60c759bc567dfe0b20ec6abb/original/validating-the-charmm36m-protein-force-field-with-lj-pme-reveals-altered-hydrogen-bonding-dynamics-under-elevated-pressures.pdf |
61662be22aca53490f61d08f | 10.26434/chemrxiv-2021-477kn | Capturing the Most Active State of a Palladium(0) Cross-Coupling Catalyst | Zerovalent palladium complexes are ubiquitous active species in modern cross-coupling reactions that comprise many premier methods for the construction of C–C and C–heteroatom bonds in organic synthesis. While palladium(0) complexes stabilized by two or more dative ligands are widely known, the most active form of Pd(0) coordinated by a single ancillary ligand (“monoligated Pd(0)”) has long eluded direct characterization. We report the synthesis and unambiguous solution- and solid-state characterization of functionally 12-electron Pd(0) complexes coordinated by a single tri(1-adamantyl)phosphine (PAd3) ligand. Access to these fleeting intermediates was achieved by enabling B-to-Pd transmetalation reactions that occur at cryogenic temperature. This work opens new avenues to experimentally interrogate highly reactive on-cycle Pd(0) catalysts and their structure-dependent reactivity and speciation, which should be broadly informative in continuing studies of catalytic processes featuring the prevalent Pd(0)/Pd(II) redox couple. | Sii Hong Lau; Liye Chen; Illia Kevlishvili; Katherine Davis; Peng Liu; Brad Carrow | Organic Chemistry; Catalysis; Organometallic Chemistry; Catalysis; Coordination Chemistry (Organomet.); Kinetics and Mechanism - Organometallic Reactions | CC BY NC ND 4.0 | CHEMRXIV | 2021-10-13 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/61662be22aca53490f61d08f/original/capturing-the-most-active-state-of-a-palladium-0-cross-coupling-catalyst.pdf |
66fee45012ff75c3a153662a | 10.26434/chemrxiv-2024-pz7dv | Detection of Putative Ligand Dissociation Pathways in Proteins using Site-Identification by Ligand Competitive Saturation | Drug efficacy often correlates better with dissociation kinetics than binding affinity alone. To study binding kinetics computationally, it is necessary to identify all possible ligand dissociation pathways. The site identification by ligand competitive saturation (SILCS) method involves the pre-computation of a set of maps (FragMaps), which describe the free energy landscapes of typical chemical functionalities in and around a target protein or RNA. In the current work, we present and implement a method to use SILCS to identify ligand dissociation pathways. The A* pathfinding algorithm is utilized to enumerate ligand dissociation pathways between the ligand binding site and the surrounding bulk solvent environment defined on evenly spaced points around the protein based on a Fibonacci lattice. The cost function for the A* algorithm is calculated using the SILCS exclusion maps and the SILCS grid free energy scores thereby identifying paths that account for local protein flexibility and potential favorable interactions with the ligand. By traversing all evenly distributed bulk solvent points around the protein, all possible dissociation pathways are located and clustered to identify general ligand unbinding pathways. The procedure is verified using proteins studied previously with enhanced sampling MD techniques and is shown to be capable of capturing important ligand dissociation routes in a highly computationally efficient manner. The identified pathways will act as the foundation for determining ligand dissociation kinetics using SILCS free energy profiles, which will be described in a subsequent manuscript. | Wenbo Yu; David Weber; Alex MacKerell | Theoretical and Computational Chemistry; Biological and Medicinal Chemistry; Biophysics; Drug Discovery and Drug Delivery Systems; Computational Chemistry and Modeling | CC BY NC ND 4.0 | CHEMRXIV | 2024-10-07 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/66fee45012ff75c3a153662a/original/detection-of-putative-ligand-dissociation-pathways-in-proteins-using-site-identification-by-ligand-competitive-saturation.pdf |
65f9adfce9ebbb4db9095c8f | 10.26434/chemrxiv-2024-nkzks-v2 | Synthesis of Iso-Dimethyltryptamines and Biological Analysis in a Model of Light-Induced Retinal Degeneration | IsoDMT analogs with heterocyclic substitutions at the indole C(3) were prepared in a hydrogen-autotransfer (HA) alkylation and tested in combination with natural and unnatural clavine alkaloids in a model of light-induced retinal degeneration for protection against retinal degeneration. As assessed with OCT and ERG, three compounds showed better efficacy than positive-control bromocriptine at equivalent systemically administered doses. These studies provide further insight into the role that 5-HT receptors play in ocular diseases. | Ethan Pazur; Anna Kalatanova; Nikhil Tasker; Katri Vainionpää; Henri Leinonen; Peter Wipf | Biological and Medicinal Chemistry; Organic Chemistry; Natural Products; Organic Synthesis and Reactions; Drug Discovery and Drug Delivery Systems | CC BY NC ND 4.0 | CHEMRXIV | 2024-03-20 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/65f9adfce9ebbb4db9095c8f/original/synthesis-of-iso-dimethyltryptamines-and-biological-analysis-in-a-model-of-light-induced-retinal-degeneration.pdf |
6386003e94ff6039ba43bc5d | 10.26434/chemrxiv-2022-gdqvc | The Interaction between TEMPO Radicals and Gold Surfaces | Organic radical molecules are, due to their relevance for spintronics and fundamental interest, studied in mechanically controlled break junctions. It is often assumed that organic radicals are anchored to the gold electrodes by designated linker thiol groups, with the radical substituents far from the electrodes. However, the interaction between a radical substituent and gold, in addition to the functional groups designed for anchoring the molecule, could influence the interaction between the whole molecule and the surface. Although some relevant experiments have been reported, the findings are inconsistent. To elucidate a possible influence, we discuss the interaction between a commonly used nitroxyl radical, (2,2,6,6-tetramethylpiperidin-1-yl)oxidanyl (TEMPO), with gold electrode surfaces by density functional theory methods, combined with empirical dispersion corrections. Within the uncertainty inherent in this methodology, our results suggest that the interaction between TEMPO and gold is made up of two competitive and complementary contributions: direct binding between the nitroxyl and gold adatoms, and dispersion interactions between bulky methyl groups and the surface (which is more pronounced for clean Au(111) surfaces but also prevents direct binding in case). Importantly, the overall interaction is not negligible and is even comparable to some commonly used anchoring groups (e.g., amino groups). This may have consequences for interpreting conductance and magnetoresistance data on organic radicals in molecular junctions. | Haitao Zhang; Carmen Herrmann | Theoretical and Computational Chemistry; Physical Chemistry; Nanoscience; Theory - Computational; Physical and Chemical Properties; Surface | CC BY NC ND 4.0 | CHEMRXIV | 2022-11-30 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/6386003e94ff6039ba43bc5d/original/the-interaction-between-tempo-radicals-and-gold-surfaces.pdf |
63037035d858fb3fca57fc0c | 10.26434/chemrxiv-2022-nq1wn-v2 | Neither too little nor too much: finding the ideal proportion of excipients | Excipient’s homogeneity is of paramount importance during the development of pharmaceutical formulations due to its relation to stability, safety and efficacy. A direct and unique approach to evaluate such property is 3D Raman imaging. This technique characterizes the surface and inner part of preformulation samples, allowing to determine phase separation in the early stages of pharmaceutical development. Aiming to promote controlled release of the local anesthetic butamben (BTB), confocal 3D Raman microscopy was used to obtain its optimal proportion in Apifil®, Capryol® 90 and Transcutol®. Even if the microscopic images of some samples displayed very homogeneous surfaces, analysis of 3D maps showed that chemical distribution throughout the material was different. To investigate how concentration affects the homogeneity, mixture experimental design (DoE) was employed. From this analysis, it was revealed that correct amount of Capryol® 90 enhances both miscibility and solubility. Furthermore, suitable miscibility was observed in two ratio proportions of excipients: Solution 1: Apifil® 30.00%, Capryol 20.00% and Transcutol 10.00% (w/w), with a desirability of 0.783; and Solution 2: Apifil® 25.00%, Capryol 25.00% and Transcutol 10.00% (w/w), with 0.742 desirability. These results unequivocally demonstrated that confocal Raman microscopy combined to DoE can bring pharmaceutical development to a higher level. | Hery Mitsutake; Gustavo Henrique Rodrigues da Silva; Márcia Cristina Breitkreitz; Eneida de Paula; Heloisa Nunes Bordallo | Materials Science; Analytical Chemistry; Imaging; Microscopy; Spectroscopy (Anal. Chem.) | CC BY NC ND 4.0 | CHEMRXIV | 2022-08-22 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/63037035d858fb3fca57fc0c/original/neither-too-little-nor-too-much-finding-the-ideal-proportion-of-excipients.pdf |
6688085c01103d79c51d2892 | 10.26434/chemrxiv-2024-296c0 | Atomic-Precision Non-van der Waals 2D Structures: Superconductivity in π-d Conjugated Coordination Polymers | Two-dimensional conjugated coordination polymers (2D c-CPs) exhibit exceptional charge transport properties. Among them, copper-based benzenehexathiol coordination polymer (Cu-BHT) is a rare superconductor. However, the precise atomic structure of Cu-BHT remains elusive, hindering the understanding of the origin of superconductivity in 2D c-CPs. Here, single crystals of Cu3BHT with the high crystallinity have been achieved, revealing a quasi-2D kagome structure with non-van der Waals interlayer Cu-S covalent bonds. Cu3BHT single crystal exhibits intrinsic metallic behavior, with conductivity reaching 10E3 S/cm at 300 K and 10E4 S/cm at 2 K. Notably, superconductivity in Cu3BHT crystals was observed for the first time at 0.25 K, attributed to the enhanced electron-electron interactions and electron-phonon coupling induced by non-van der Waals 2D structures. The discovery of this clear correlation between atomic-precise crystal structure and electrical properties lays a crucial foundation for the emergence of new superconductor CPs, aiming for revolutionizing the future quantum devices. | Zhichao Pan; Xing Huang; Yunlong Fan; Shaoze Wang; Yiyu Liu; Xuzhong Cong; Tingsong Zhang; Shichao Qi; Ying Xing; Yu-Qing Zheng; Jian Li; Xiaoming Zhang; Wei Xu; Lei Sun; Jian Wang; Jin-Hu Dou | Physical Chemistry; Materials Science; Hybrid Organic-Inorganic Materials; Physical and Chemical Properties; Materials Chemistry; Crystallography | CC BY NC ND 4.0 | CHEMRXIV | 2024-07-08 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/6688085c01103d79c51d2892/original/atomic-precision-non-van-der-waals-2d-structures-superconductivity-in-d-conjugated-coordination-polymers.pdf |
67dd69b081d2151a0251d3c6 | 10.26434/chemrxiv-2025-rdq9k | Modulating Electrostatic Interactions to Control the Analyte Transport in Nanochannels | Ion-receptor binding is a key mechanism for various biological responses that greatly inspire biomimetic approaches in technologies ranging from nanomedicine to energy storage and active membrane separation. Interaction between analytes and nanopores has been reported to either favour the transport (electrochemical studies performed in the millimolar concentration regime) or to slow down the diffusion in nanochannels (single molecule investigations in the nanomolar range). Here, we propose a simple and inexpensive fluorescence setup for monitoring sub-micromolar diffusion, which effectively bridges these two concentration regimes, and show that at micromolar concentration, electrostatic interactions between the analyte (Ru(bpy)32+) and nanochannel walls slow down the transport by ca. 20% due to hopping diffusive behavior. The occurrence of this mechanism was previously investigated with single molecule FCS techniques, and it is here confirmed even in bulk measurements conducted at micromolar concentration. Furthermore, we demonstrate that electrostatic interactions can be (i) switched off by changing the pH to acidic, or can be (ii) finely tuned by adding a competitor divalent cation (Ca2+), which effectively competes with the cationic analyte (Ru(bpy)32+) for the negatively charged walls, allowing smoother diffusion through the nanochannels. | H. Samet Varol; Matteo Cingolani; Francesco Casnati; Damiano Genovese | Physical Chemistry; Materials Science; Nanoscience; Nanostructured Materials - Materials; Nanofluidics; Transport phenomena (Physical Chem.) | CC BY NC ND 4.0 | CHEMRXIV | 2025-03-24 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/67dd69b081d2151a0251d3c6/original/modulating-electrostatic-interactions-to-control-the-analyte-transport-in-nanochannels.pdf |
61bce3975b23d4bd2601336f | 10.26434/chemrxiv-2021-4jl66 | Modeling and characterization of exciplexes in photoredox CO2 reduction: Insights from quantum chemistry and fluorescence spectroscopy | Interactions between excited state arenes and amines can lead to the formation of structures with distinct emission behavior. These excited state complexes or exciplexes can reduce the ability of the arene to participate in other reactions, such as CO2 reduction, or increase the likelihood of degradation via Birch reduction. Exciplex geometries are necessary to understand photophysical behavior and probe degradation pathways but are challenging to calculate. We establish a detailed computational protocol for calculation, verification, and characterization of exciplexes. Using fluorescence spectroscopy, we first demonstrate the formation of exciplexes between excited state oligo-(p-phenylene) (OPP), shown to successfully carry out CO2 reduction, and triethylamine (TEA). Time-dependent density functional theory (TDDFT) is employed to optimize the geometries of these exciplexes, which are validated by comparing both emission energies and their solvatochromism with experiment. Excited state energy decomposition analysis confirms the predominant role played by charge transfer interactions in the red-shift of emissions relative to the isolated excited state OPP*. We find that although the exciplex emission frequency depends strongly on solvent dielectric, the extent of charge separation in an exciplex does not. Our results also suggest that the formation of solvent-separated ionic radical states upon complete electron transfer competes with exciplex formation in higher dielectric solvents, thereby leading to
reduced exciplex emission intensities in fluorescence experiments. | Kareesa Kron; Jonathan Ryan Hunt; Jahan Dawlaty; Shaama Mallikarjun Sharada | Theoretical and Computational Chemistry; Organic Chemistry; Catalysis; Photochemistry (Org.); Computational Chemistry and Modeling; Redox Catalysis | CC BY NC ND 4.0 | CHEMRXIV | 2021-12-20 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/61bce3975b23d4bd2601336f/original/modeling-and-characterization-of-exciplexes-in-photoredox-co2-reduction-insights-from-quantum-chemistry-and-fluorescence-spectroscopy.pdf |
64a258b86e1c4c986bb87759 | 10.26434/chemrxiv-2023-r42hj | PFAS science and regulation should be reconsidered using fluorine-specific physical chemistry | Poly- and perfluoroalkyl substances (PFAS) have been widely used due to their unique properties, such as water and oil repellence, chemical and physical resistance, and surfactant nature. However, many studies have revealed unfavourable properties of PFAS, especially their long-range transport potential, environmental persistence and harmful effects on human health and ecosystems. Production and use of a few PFAS are restricted. Many alternatives have been introduced to the market, but some are as problematic as the original PFAS (i.e., regrettable substitution). This has led to discussions about regulation of PFAS as a chemical class, but a lack of PFAS-specific scientific knowledge on their physical properties prevents a detailed discussion on PFAS regulation. The Stratified Dipole-Arrays (SDA) theory provides fluorine-specific science to understand the unique properties of PFAS. It decisively reveals that the material properties of a single molecule and molecular aggregates are intrinsically different and therefore must be strictly discriminated. In addition, PFAS with longer fluoroalkyl chains containing seven or more carbon–fluorine (CF2) groups can self-aggregate due to the combinatorial effect of the dipole moment along the carbon–fluorine bond and the helical conformation around the molecular axis, which determines the properties of PFAS. The SDA theory also shows that shorter PFAS do not self-aggregate and act as single molecules with dipoles on their surfaces, which can interact with biological molecules. Expanding the SDA theory to incorporate the interaction between PFAS and biomolecules will improve understanding of the biological effects of PFAS. Comprehensive understanding of the nature of PFAS is required for their sound regulation, production and use. | Takeshi Hasegawa; Shoji Nakayama | Physical Chemistry; Materials Science; Earth, Space, and Environmental Chemistry; Thin Films; Interfaces; Surface | CC BY NC ND 4.0 | CHEMRXIV | 2023-07-05 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/64a258b86e1c4c986bb87759/original/pfas-science-and-regulation-should-be-reconsidered-using-fluorine-specific-physical-chemistry.pdf |
60c741aaf96a0023a72864ae | 10.26434/chemrxiv.8107772.v1 | Monitoring DNA-Ligand Interactions in Living Human Cells Using High-Resolution NMR Spectroscopy | High-resolution studies of DNA–ligand interactions in the cellular environment are problematic due to the lack of suitable biophysical tools. To address this issue, we developed an in-cell NMR-based approach for monitoring DNA–ligand interactions inside the nuclei of living human cells. Our method relies on the acquisition of high-resolution NMR data of cells electroporated with pre-formed DNA-ligand complex. The impact of the intracellular environment on the integrity of the complex is assessed on the basis of in-cell NMR signals from unbound and ligand-bound forms of a given DNA target. By using this technique, we studied complexes of model DNA fragments and four ligands, representative of DNA minor-groove binders (netropsin) or ligands binding to DNA pairing defects (naphthalenophanes). We demonstrate that some of the <i>in vitro</i> validated ligands retain their ability to form stable on-target DNA interactions <i>in situ</i>, while other<i> </i>lose this ability due to off-target interactions with genomic DNA as well as cellular metabolic components. Collectively, our data suggest that direct evaluation of behavior of drug-like molecules in the intracellular environment provides important insights for the design and development of DNA-binding ligands with the desired biological action and minimal side effects resulting from off-target binding.<br /><div><br /></div> | Michaela Krafcikova; Simon Dzatko; Coralie Caron; Anton Granzhan; Radovan Fiala; Tomas Loja; Marie-Paule Teulade-Fichou; Tomas Fessl; Rober Hansel-Hertsch; Jean-Louis Mergny; Silvie Foldynova-Trantirkova; Lukas Trantirek | Biochemistry; Biophysics; Cell and Molecular Biology; Drug Discovery and Drug Delivery Systems | CC BY NC ND 4.0 | CHEMRXIV | 2019-05-10 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/60c741aaf96a0023a72864ae/original/monitoring-dna-ligand-interactions-in-living-human-cells-using-high-resolution-nmr-spectroscopy.pdf |
60c740c8ee301c4aa3c78b00 | 10.26434/chemrxiv.7834940.v1 | Synthesis of Nitrile-Bearing Quaternary Centers via an Equilibrium-Driven Transnitrilation and Anion-Relay Strategy | The efficient preparation of nitrile-containing building blocks is of interest due to their utility as synthetic intermediates and their prevalence in pharmaceuticals. As a result, significant efforts have been made to develop methods to access these motifs which rely on safer and non-toxic sources of CN. Herein, we report that 2-methyl-2-phenylpropanenitrile is an efficient, non-toxic, electrophilic CN source for the synthesis of nitrile-bearing quaternary centers via a thermodynamic transnitrilation and anion-relay strategy. This one-pot process leads to nitrile products resulting from the gem-difunctionalization of alkyl lithium reagents.<br /> | Sebastien Alazet; Michael West; Purvish Patel; Sophie Rousseaux | Organic Compounds and Functional Groups; Organic Synthesis and Reactions; Drug Discovery and Drug Delivery Systems; Pharmaceutical Industry | CC BY NC ND 4.0 | CHEMRXIV | 2019-03-13 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/60c740c8ee301c4aa3c78b00/original/synthesis-of-nitrile-bearing-quaternary-centers-via-an-equilibrium-driven-transnitrilation-and-anion-relay-strategy.pdf |
67c011156dde43c908ad7530 | 10.26434/chemrxiv-2025-r09n8 | Enhancing Triplet Harvesting in Inverted Singlet-Triplet Gap Molecules through Mechanistic Understanding | Molecules with an inverted singlet-triplet gap violate Hund’s rule and offer promising applications in optoelectronics and photocatalysis. However, understanding the mechanistic factors governing electronic transitions is crucial for optimizing their performance. In this work, we employ the nuclear ensemble method combined with high-level electronic structure calculations to investigate the role of vibrational effects in four azaphenalene-based molecules. Our results reveal that maximizing the thermodynamic driving force for reverse intersystem crossing is not necessarily a desired strategy for efficient triplet harvesting. Nevertheless, due to the vibronic coupling, molecular cores with small negative gaps are a promising starting point as appropriate functionalization can decrease delayed fluorescence lifetimes despite the gap moving toward positive values. These findings provide new design principles for developing efficient triplet-harvesting materials, emphasizing the need to control vibrational and symmetry effects to balance radiative and non-radiative transitions effectively. | Laure de Thieulloy; Leonardo Evaristo de Sousa; Piotr de Silva | Theoretical and Computational Chemistry; Physical Chemistry; Photochemistry (Physical Chem.); Physical and Chemical Processes; Quasiparticles and Excitations; Materials Chemistry | CC BY NC ND 4.0 | CHEMRXIV | 2025-02-28 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/67c011156dde43c908ad7530/original/enhancing-triplet-harvesting-in-inverted-singlet-triplet-gap-molecules-through-mechanistic-understanding.pdf |
60c7442d9abda22119f8c2e4 | 10.26434/chemrxiv.9750764.v1 | Periodicity in Structure, Bonding, and Reactivity for P-Block Complexes of a Geometry-Constraining Triamide Ligand | The use of pincer ligands to access non-VSEPR
geometries at main-group centers is an emerging strategy for eliciting new
stoichiometric and catalytic reactivity. As part of this effort, several
different tridentate trianionic substituents have to date been employed at a
range of different central elements, providing a patchwork dataset that
precludes rigorous structure-function correlation. Here we report an analysis
of periodic trends in structure (solid, solution, and gas phase), bonding, and
reactivity based on systematic variation of the central element (P, As, Sb, or
Bi) with retention of a single tridentate triamide substituent. In this
homologous series, the central element can adopt either a bent or planar
geometry. The tendency to adopt planar geometries increases descending the
group with the phosphorus triamide (<b>1</b>) and its arsenic congener (<b>2</b>)
exhibiting bent conformations, and the antimony (<b>3</b>) and bismuth (<b>4</b>)
analogues exhibiting a predominantly planar structure in solution. This trend
has been rationalized using the energy decomposition analysis. A rare
phase-dependent dynamic covalent dimerization was observed for <b>3</b> and the
associated thermodynamic parameters were established quantitatively. Planar
geometries were found to engender lower LUMO energies and smaller band gaps as
compared to bent ones, resulting in different reactivity patterns. These
results provide a benchmark dataset to guide further research in this rapidly
emerging area. | Katherine Marczenko; Joseph A Zurakowski; Marcus B. Kindervater; Samantha Jee; Toren Hynes; Nicholas Roberts; Seoyeon Park; Ulrike Werner-Zwanziger; Michael Lumsden; David N. Langelaan; Saurabh Chitnis | Bonding; Coordination Chemistry (Inorg.); Ligands (Inorg.); Main Group Chemistry (Inorg.); Spectroscopy (Inorg.); Theory - Inorganic | CC BY NC ND 4.0 | CHEMRXIV | 2019-08-30 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/60c7442d9abda22119f8c2e4/original/periodicity-in-structure-bonding-and-reactivity-for-p-block-complexes-of-a-geometry-constraining-triamide-ligand.pdf |
60c74d27bb8c1ab7013db54e | 10.26434/chemrxiv.12593429.v1 | Novel Fidaxomicin Antibiotics through Site-Selective Catalysis | <div><div><div><p>Fidaxomicin (FDX) is a marketed antibiotic for the treatment Clostridium difficile infections (CDI). Although showing interesting antibacterial properties against many Gram-positive bacteria, the application of this antibiotic is currently limited to treatment of CDI. Semisynthetic modifications present a promising strategy to improve its pharmacokinetic properties and also circumvent resistance development by broadening the structural diversity of derivatives. Based on a rational design using a cryo-EM structure analysis, we implemented two strategic site- selective catalytic reactions with a special emphasis to study the role of the carbohydrate units. Site-selective introduction of various ester moieties on the noviose as well as a Tsuji-Trost type rhamnose cleavage allowed the synthesis of novel fidaxomicin analogs with promising antibacterial activities against C. difficile and M. tuberculosis.</p></div></div></div> | David Dailler; Andrea Dorst; Daniel Schäfle; Peter Sander; Karl Gademann | Natural Products; Organic Synthesis and Reactions; Drug Discovery and Drug Delivery Systems; Microbiology; Homogeneous Catalysis; Organocatalysis | CC BY NC ND 4.0 | CHEMRXIV | 2020-07-02 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/60c74d27bb8c1ab7013db54e/original/novel-fidaxomicin-antibiotics-through-site-selective-catalysis.pdf |
6331bd652984c95fb56dc2ed | 10.26434/chemrxiv-2022-dsl74-v2 | Statistical Mechanics of Dimerizations and its Consequences for Small Systems | Utilizing a statistical mechanics framework, we derive the expression of the equilibrium constant for dimerization reactions. An important feature arising from the derivation is the necessity to include two-body correlations between monomer's particles, reminiscent to those recently found crucial for binding reactions. However in (homo-) dimerizations, particles of the same type associate, and therefore, self-correlations are excluded. As a result, the mathematical form of the equilibrium constant differs from the well-known expression given in textbooks. For systems with large number of particles the discrepancy is negligible, whereas, for finite systems it is significant. Rationalized by collision probability between monomers, the bimolecular rate for dimer formation is proportional to concentration the same way correlations are accounted for. That is average of squared, and not square of averaged, monomer concentration should be considered in such a way that inconceivable collisions between a tagged particle with itself are excluded. Another consequence emerging from these two-body correlations, is an inhomogeneous function behavior of system's properties when scaling-down the system to a regime smaller than the thermodynamic limit. Thus, averages of properties observed at small systems are different than those observed at macroscopic systems. When applied to the size-dependent composition of the system, we further demonstrate the equilibrium concentration of the dimer (or monomer) can be obtained from only the magnitudes of fluctuations in the system. All predictions are verified by Monte Carlo and molecular dynamics simulations. | Ronen Zangi | Theoretical and Computational Chemistry; Physical Chemistry; Chemical Kinetics; Statistical Mechanics; Thermodynamics (Physical Chem.) | CC BY NC ND 4.0 | CHEMRXIV | 2022-09-27 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/6331bd652984c95fb56dc2ed/original/statistical-mechanics-of-dimerizations-and-its-consequences-for-small-systems.pdf |
615dc8540ad1ffee1c8c32bf | 10.26434/chemrxiv-2021-mvjqq-v2 | Using transient equilibria (TREQ) to measure the thermodynamics of slowly assembling supramolecular systems | Supramolecular chemistry involves the non-covalent assembly of monomers into materials with unique properties and wide-ranging applications. Thermal analysis is a key analytical tool in this field, as it provides quantitative thermodynamic information on both the structural stability and nature of the underlying molecular interactions. However there exist many supramolecular systems whose kinetics are so slow under conditions approaching equilibrium that thermodynamic data are inaccessible. We have developed a simple and rapid spectroscopic method for extracting thermodynamic parameters from these systems. It is based on repeatedly raising and lowering the temperature during assembly and identifying the points of transient equilibrium as they are passed on the up- and down-scans. In a proof-of-principle application to the co-assembly of polydeoxyadenosine containing 15 adenosines (polyA15) and cyanuric acid (CA), we found that roughly 30% of the CA binding sites on the polyA chains were unoccupied, with implications for the assembly of high-valence systems. | Christopher Hennecker; Christophe Lachance-Brais; Hanadi Sleiman; Anthony Mittermaier | Physical Chemistry; Analytical Chemistry; Biophysical Chemistry; Self-Assembly; Spectroscopy (Physical Chem.); Materials Chemistry | CC BY NC ND 4.0 | CHEMRXIV | 2021-10-15 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/615dc8540ad1ffee1c8c32bf/original/using-transient-equilibria-treq-to-measure-the-thermodynamics-of-slowly-assembling-supramolecular-systems.pdf |
63597bcccf6de9ddde23a4c4 | 10.26434/chemrxiv-2022-7r1k8 | Modular synthesis of nimbolide and its analogues as PARP1 trapping inducers | PARP1 inhibitors (PARPi) has reshaped the clinical treatment of cancer patients with germline BRCA1/2 mutations presumably due to their ability to induce PARP1 trapping. Since PARPi resistance is frequently observed, there is still an unmet need to develop next generation PARP1-targeting agents for a more complete and sustained therapeutic effect. Historically, natural products have played pivotal roles in anticancer drug development by providing novel targets and mechanism of actions. In our recent discovery20, a ring seco-C limonoid natural product, nimbolide, was found to inhibit a Poly-ADPRibosylation (PARylation)-dependent ubiquitin E3 ligase RNF114, and in doing so, induce the “super trapping” of both PARylated PARP1 and PAR-dependent DNA repair factors. Modular access to nimbolide and its analogues represents an opportunity to develop novel agents as the second generation PARP1-targeting agents for the treatment
of BRCA-deficient cancers. Here, we report a convergent synthesis of nimbolide through a pharmacophore-directed, late-stage coupling strategy. The broad generality of this route is demonstrated through the synthesis of a variety of analogues with their preliminary cellular cytotoxicity and PARP1 trapping activity reported. | Tian Qin; Heping Deng; Hejun Deng; Chiho Kim; Peng Li; Xudong Wang; Yonghao Yu | Organic Chemistry | CC BY NC ND 4.0 | CHEMRXIV | 2022-10-27 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/63597bcccf6de9ddde23a4c4/original/modular-synthesis-of-nimbolide-and-its-analogues-as-parp1-trapping-inducers.pdf |
6622898a418a5379b0325b80 | 10.26434/chemrxiv-2024-b0bbz | Exploring Extended Warheads of Reversible and Irreversible Cysteine-Targeted Covalent Kinase Inhibitors | In designing covalent kinase inhibitors (CKIs), the inclusion of electrophiles as attacking warheads demands careful choreography, ensuring not only their presence on the scaffold moiety but also their precise interaction with nucleophiles in the binding sites. Given the limited number of known electrophiles, exploring adjacent chemical space to broaden the palette of available electrophiles capable of covalent inhibition, is desirable. Here, we perform a systematic analysis of the characteristics of warheads and corresponding adjacent fragments for use in CKI design. We first collect all the released cysteine-targeted CKIs from multiple databases and create one CKI dataset containing 16,961 kinase-inhibitor data points from 12,381 unique CKIs covering 146 kinases with accessible cysteines in their binding pockets. Then we analyze this dataset, focusing on the extended warheads (i.e., warheads + adjacent fragments) — including 30 common warheads and 1344 unique adjacent fragments. Thus, we provide structural insights, and delineate chemical properties, and patterns in these extended warheads. Notably, we highlight the privileged patterns observed within reversible CKIs for the popular warheads cyanoacrylamide and aldehyde. This study provides medicinal chemists with novel insights into extended warheads and a comprehensive source of adjacent fragments, thus guiding the design, synthesis, and optimization of CKIs. | zheng zhao; Philip Bourne | Theoretical and Computational Chemistry; Biological and Medicinal Chemistry; Bioinformatics and Computational Biology; Drug Discovery and Drug Delivery Systems; Theory - Computational | CC BY NC ND 4.0 | CHEMRXIV | 2024-04-22 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/6622898a418a5379b0325b80/original/exploring-extended-warheads-of-reversible-and-irreversible-cysteine-targeted-covalent-kinase-inhibitors.pdf |
675073b4f9980725cf07b0ef | 10.26434/chemrxiv-2024-42pt6 | Sphingomyelin Slows Interfacial Hydrogen-bonding Dynamics in Lipid Membranes | Hydrogen bonding at lipid interfaces partly determines membrane structure, heterogeneity, and dynamics. Given the chemical diversity of lipids, it is important to understand the relationship between lipid composition and interfacial H-bond dynamics. Here we investigate the role of palmitoyl sphingomyelin (PSM) in modulating interfacial H-bond networks in binary mixtures with dipalmitoyl phosphatidylcholine (DPPC) using a combination of ultrafast two-dimensional infrared (2D IR) spectroscopy and molecular dynamics (MD) simulations. We find that analysis of 2D IR spectra of the amide carbonyl is subtle, requiring a careful accounting of the heterogeneous H-bond environment of the amide. The amide groups in PSM, acting as H-bond donors, partially replace water-mediated interactions at lipid carbonyls, with the number of lipid-lipid H-bonds constituting up to 20% of the total. These interactions create comparatively stable hydrogen-bond networks that significantly slow interfacial dynamics. The comparison between experiments and simulations reveals composition-dependent H-bond ensembles for ester and amide carbonyls, with increased H-bond populations and slower dynamics with higher PSM concentrations. 2D IR spectra show that interfacial H-bond dynamics slow by up to 45% in an equimolar mixture of the two lipids compared to DPPC alone. This study highlights PSM's dual role in H-bonding, which increases membrane viscosity and stabilizes lipid interfaces, providing molecular insights into the role of sphingolipids in cell membranes. These findings further emphasize the synergy of experimental and computational approaches for extracting molecular-level insights into interfacial lipid-lipid and lipid-water interactions in heterogeneous membranes. | Cong Xu; James Fitzgerald III; Edward Lyman; Carlos Baiz | Physical Chemistry; Biophysical Chemistry | CC BY NC ND 4.0 | CHEMRXIV | 2024-12-09 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/675073b4f9980725cf07b0ef/original/sphingomyelin-slows-interfacial-hydrogen-bonding-dynamics-in-lipid-membranes.pdf |
67dd920f81d2151a0255024c | 10.26434/chemrxiv-2025-4rdbn | Assessing Spin-flip Time-Dependent Density-Functional Based Tight-Binding For Describing Photoisomerisation Reactions | Photoisomerisation of molecular systems are important as building blocks for light driven molecular motors. Understanding the effect of chemical substitution on the underlying mechanisms and the isomerisation quantum yields is crucial for optimizing their functionality. In this study, we develop, implement and evaluate the performance of the spin-flip time-dependent density-functional based tight-binding (SF-TDDFTB) as a cost-effective approach for simulating the excited-state potential energy surfaces of several photoisomerising chromophores. By comparing the results with SF-TDDFTB with all-electron MRSF-TDDFT, we investigate the accuracy of the tight-binding formalism in capturing the correct potential energy surface leading to the photoisomerization pathways for well-known photoisomerisation reactions of a protonated Schiff base, an oxidondole molecular motor, the green fluorescent protein chromophore and a photodrug. Our findings demonstrate that the SF-TDDFTB method offers a balanced trade-off between computational efficiency and accuracy. These results pave the way for more efficient computational models for studying the photoisomerisation reactions of complex molecular systems. | Miquel Huix-Rotllant; Woojin Park; Mohsen Mazaherifar; Cheol Ho Choi | Theoretical and Computational Chemistry; Computational Chemistry and Modeling; Theory - Computational | CC BY 4.0 | CHEMRXIV | 2025-03-24 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/67dd920f81d2151a0255024c/original/assessing-spin-flip-time-dependent-density-functional-based-tight-binding-for-describing-photoisomerisation-reactions.pdf |
6206e2737a054a1a160a810a | 10.26434/chemrxiv-2022-x058p | Evidence for Low-valent Electronic Configurations in Iron–Sulfur Clusters | Although biological iron-sulfur (Fe–S) clusters perform some of the most difficult redox reactions in Nature, they are thought to be composed exclusively of Fe2+ and Fe3+ ions, as well as mixed-valent pairs with average oxidation states of Fe2.5+. We herein show that Fe–S clusters formally composed of these valences can access a wider range of electronic configurations—in particular, those featuring low-valent Fe1+ centers. We demonstrate that CO binding to a synthetic [Fe4S4]0 cluster supported by N-heterocyclic carbene ligands induces generation of Fe1+ centers via intracluster electron transfer, wherein a neighboring pair of Fe2+ sites reduces the CO-bound site to a low-valent Fe1+ state. Similarly, CO binding to an [Fe4S4]+ cluster induces electron delocalization with a neighboring Fe site to form a mixed-valent Fe1.5+Fe2.5+ pair in which the CO-bound site adopts partial low-valent character. These low-valent configurations engender remarkable C–O bond activation without having to traverse highly negative and physiologically inaccessible Fe2+/Fe1+ redox couples. | Alexandra Brown; Niklas Thompson; Daniel Suess | Inorganic Chemistry; Bioinorganic Chemistry; Bonding; Small Molecule Activation (Inorg.) | CC BY NC ND 4.0 | CHEMRXIV | 2022-02-14 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/6206e2737a054a1a160a810a/original/evidence-for-low-valent-electronic-configurations-in-iron-sulfur-clusters.pdf |
66033bf59138d23161602c69 | 10.26434/chemrxiv-2024-t5tfh-v2 | A Polarizable Valence Electron Density Based Force Field for High-Energy Interactions between Atoms and Molecules | High-accuracy molecular force field models suited for hot gases and plasmas are not as abundant as those geared towards ambient pressure and temperature conditions. Here we present an improved version of our previous electron- density based force field model that can account for polarization effects by adjusting the atomic valence electron contributions to match ab initio calculated Mulliken partial charges. Using a slightly modified version of the Hohenberg-Kohn theorem, we also present an improved theoretical formulation of our model when dealing with systems with degenerate ground states. Preliminary results obtained from this methodology for water dimer calculations using CCSD(T)/cc-pVTZ and CCSD(T)/CEP-31G level of theory are presented using an order ten approximation. Further improvements include the additional interaction components with fictitious non-spherically symmetric, yet atom-centered, electron densities and fitting the exchange and correlation coefficients against analytical expressions. The latter removes all unphysical oscillations that are observed in the previous non-polarizable variant of our force field. | José Romero; Paulo Limão-Vieira; Thana Maihom; Kersti Hermansson; Michael Probst | Theoretical and Computational Chemistry; Physical Chemistry; Computational Chemistry and Modeling; Theory - Computational; Chemoinformatics - Computational Chemistry | CC BY 4.0 | CHEMRXIV | 2024-03-27 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/66033bf59138d23161602c69/original/a-polarizable-valence-electron-density-based-force-field-for-high-energy-interactions-between-atoms-and-molecules.pdf |
631b5e635351a34068f490a5 | 10.26434/chemrxiv-2022-1m9q5 | Synthesis and characterization of colloidal quantum dot
superparticles - plasmonic gold nanoshell hybrid nanostructures | Coupling an ensemble of fluorescent emitters with a plasmonic resonator opens opportunities to
control their emission properties at the nanoscale. However, synthesis of such hybrid colloidal
nanostructures is challenging. In this manuscript, we report the synthesis of compact assemblies of
semiconductor quantum dots encapsulated into a gold nanoshell. We discuss how the synthesis
parameters enable full control of the architecture of the nanostructure. Optical properties are
discussed and compared to theoretical models. Coupling of the emitters to the gold layer is evidenced
by an acceleration of the photoluminescence decay and results in an improvement of the
photostability. | Alexandra Bogicevic; Xiangzhen Xu; Stéphanie Buil; Christophe Arnold; Jean-Pierre Hermier; Thomas Pons; Nicolas Lequeux | Nanoscience; Nanostructured Materials - Nanoscience; Plasmonic and Photonic Structures and Devices | CC BY NC ND 4.0 | CHEMRXIV | 2022-09-14 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/631b5e635351a34068f490a5/original/synthesis-and-characterization-of-colloidal-quantum-dot-superparticles-plasmonic-gold-nanoshell-hybrid-nanostructures.pdf |
66ffc4dccec5d6c1421e8745 | 10.26434/chemrxiv-2024-qwqzt | Experimental Study on the Control of Wire Pickling Solution Concentration | Using diffusion dialysis technology, hydrochloric acid pickling solution from wire surface treatment is recovered. By adding new hydrochloric acid, the pickling solution maintains the concentration necessary for regular production, allowing continuous recycling in wire pickling to reduce the consumption of new hydrochloric acid. This study investigates the effects of the water-to-acid flow ratio, hydrochloric acid concentration, ferric chloride concentration, and receiving solution on the acid recovery rate and ferric chloride retention rate. The results indicate:
(1) The water-to-acid flow ratio and receiving solution have little impact on acid recovery;
(2) As the hydrochloric acid concentration increases, the recovery rate gradually decreases from 92% to about 85%, while the retention rate conversely increases from 75% to around 83%;
(3) As the ferric chloride concentration increases, the recovery rate slowly rises, peaking at 92% when the ferric chloride concentration reaches 150 g/L, then slightly decreases, while the retention rate shows the opposite trend;
(4) Recovered acid with a concentration of 238 g/L effectively treats rusted wire. The experiment confirms that diffusion dialysis technology can effectively reduce production costs and improve efficiency.
| Yifei Ma | Chemical Engineering and Industrial Chemistry | CC BY NC ND 4.0 | CHEMRXIV | 2024-10-09 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/66ffc4dccec5d6c1421e8745/original/experimental-study-on-the-control-of-wire-pickling-solution-concentration.pdf |
60c749a8bb8c1a09943daea5 | 10.26434/chemrxiv.12094053.v1 | Synthetic Elaboration of Native DNA by RASS (SENDR) | The controlled, site-specific ligation of molecules to native DNA remains an unanswered challenge. Herein, we report a simple solution to achieve this ligation through the tactical combination of two recently developed technologies: One for the manipulation of DNA in organic media, and another for the chemoselective labeling of alcohols. Reversible Adsorption of Solid Support (RASS) is employed to immobilize DNA and facilitate its transfer into dry acetonitrile. Subsequent ligation with P(V)-based Ψ reagents takes place in high yield with exquisite selectivity for the exposed 3’ or 5’ alcohols on DNA. This two-stage process, dubbed SENDR for Synthetic Elaboration of Native DNA by RASS, can be applied to a multitude of DNA conformations and sequences with a variety of functionalized Ψ reagents to generate useful constructs. Such entities can address numerous longstanding challenges, including the selective single coupling of DNA to proteins, ASOs, and functional small molecules, and also can allow the synthesis of doubly-labeled congeners for novel probe constructs including ones of potential interest to COVID-19 research. Finally, a prototype for the industrialization of SENDR in a kit format is presented. | Dillon T. Flood; Kyle W. Knouse; Julien C. Vantourout; Brittany Sanchez; Emily J. Sturgell; Jason Chen; Phil Baran; Philip Dawson | Bioorganic Chemistry; Organic Synthesis and Reactions; Chemical Biology | CC BY NC ND 4.0 | CHEMRXIV | 2020-04-09 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/60c749a8bb8c1a09943daea5/original/synthetic-elaboration-of-native-dna-by-rass-sendr.pdf |
60c7569e4c89192c0cad4897 | 10.26434/chemrxiv.14273987.v1 | Templating Core-Shell Particles Using Metal Ion-Chelating Biosurfactants | <p>Designer
biosurfactants can be used to stabilise and functionalise interfaces. One
particularly promising use is the stabilisation of oil-in-water emulsions,
enabling fine tuning physical, chemical and biological surface properties. The
ability of emulsion systems to carry high payloads makes them attractive for
applications in medicine, food and fragrances, and cosmetics. However, they
have limited long-term stability. Here we sought to use the metal ion-chelating
ability of the biosurfactant peptide, AM1, to precipitate the formation of a
gold metal shell on AM1-stabilised emulsions by electroless plating. We found
that replacing the commonly used zinc(II) with palladium(II) for coordination
by histidine residues of adjacent AM1 peptides produced interfacial films that
maintained elasticity at acidic pH. Proton NMR suggested a coordination
mechanism independent of the imidazole ring of the histidines. Nevertheless. stabilisation
of emulsions at low pH enabled the deposition of a gold shell, albeit by an
unexpected mechanism. We propose that gold nanoparticles forming in bulk are
adsorbed onto the peptide-stabilised interface, accumulating into a particulate
coating. The resulting one-step method for nanoparticle precipitation and shell
formation will be useful for the creation of biocompatible core-shell particles
for applications where large payloads of hydrophobic active compounds require
stability over long time periods.</p> | Ching-min Yeh; Thomas Jarrett; Yuan Gao; Chun-Xia Zhao; Andrew Whittaker; Frank Sainsbury; Alison White | Biocompatible Materials; Core-Shell Materials; Surfactants; Biopolymers; Self-Assembly | CC BY NC ND 4.0 | CHEMRXIV | 2021-03-25 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/60c7569e4c89192c0cad4897/original/templating-core-shell-particles-using-metal-ion-chelating-biosurfactants.pdf |
6319c4dcbe03b222deee6785 | 10.26434/chemrxiv-2022-d6w1n | Proton-Donating and Chemistry-Dependent Buffering Capability of Amino Acids for the Hydrogen Evolution Reaction | The hydrogen evolution reaction (HER) has been widely demonstrated to have a strong dependence on pH and on the source of protons, where a clear kinetic advantage arises in acidic conditions over near-neutral and alkaline conditions due to the switch in reactant from H3O+ to H2O. Playing on the acid/base chemistry of aqueous systems can avoid the kinetic frailties, for example, buffer systems can be used to maintain proton concentration at intermediate pH driving H3O+ reduction over H2O. In light of this, we examine the influence of amino acids on HER kinetics at platinum surfaces using rotating disk electrodes. We demonstrate that Aspartic acid (Asp) and Glutamic acid (Glu) can act not only as proton donors, but also have sufficient buffering action to sustain H3O+ reduction even at large current density. Comparing with Histidine (His) and Serine (Ser), we reveal that the buffering capacity of amino acids occurs due to the proximity of their isoelectric point (pI) and their buffering pKa. This study further exemplifies HER’s dependence on pH and pKa and that amino acids can be used to probe this relationship. | John Brown; Alexis Grimaud | Organic Chemistry; Inorganic Chemistry; Electrochemistry; Materials Chemistry | CC BY NC ND 4.0 | CHEMRXIV | 2022-09-08 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/6319c4dcbe03b222deee6785/original/proton-donating-and-chemistry-dependent-buffering-capability-of-amino-acids-for-the-hydrogen-evolution-reaction.pdf |
60c742f20f50db9b09395e1b | 10.26434/chemrxiv.8866250.v1 | Theoretical Understanding of the Thermodynamics and Interactions in Transcriptional Regulator TtgR-Ligand Binding | <p> The transcriptional regulator TtgR belongs to the TetR family of transcriptional
repressors. It depresses the transcription of the TtgABC operon and itself and thus
regulates the extrusion of noxious chemicals with efflux
pumps in bacterial cells. As the ligand binding domain of TtgR is rather flexible, it
can bind with a number of structurally diverse ligands, such as antibiotics, flavonoids and aromatic solvents. In the current work, we perform equilibrium
and nonequilibrium alchemical free energy simulation to predict the binding
affinities of a series of ligands targeting the TtgR protein and the agreement
between the theoretical prediction and the experimental result is observed.
End-point methods of MM/PBSA and MM/GBSA are also employed for comparison. We
further study the interaction maps and identify important interactions in the
protein-ligand binding cases. The current work sheds light on atomic and
thermodynamic understanding on the TtgR-ligand interactions.</p> | Zhaoxi Sun; Xiaohui Wang; John Z. H. Zhang | Bioinformatics and Computational Biology; Theory - Computational; Biophysical Chemistry; Thermodynamics (Physical Chem.) | CC BY NC ND 4.0 | CHEMRXIV | 2019-07-15 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/60c742f20f50db9b09395e1b/original/theoretical-understanding-of-the-thermodynamics-and-interactions-in-transcriptional-regulator-ttg-r-ligand-binding.pdf |
60c75761337d6c782ae29004 | 10.26434/chemrxiv.14398259.v1 | Influence of Different Polymer Belts on Lipid Properties in Nanodiscs Characterized by CW EPR Spectroscopy | Polymeric DMPC-nanodiscs from three polymers are viable membrane models. The polymers change water penetration and lipid rotational mobility within DMPC vilayers. SMA and SMA-SB have a stronger effect on lipid order than DIBMA.<br /> | Matthias Hoffmann; Jana Eisermann; Florian A. Schöffmann; manabendra das; Carolyn Vargas; Sandro Keller; Dariush Hinderberger | Biocompatible Materials; Nanostructured Materials - Materials; Organic Polymers; Polyelectrolytes - Polymers; Nanodevices; Nanostructured Materials - Nanoscience; Biochemistry; Bioengineering and Biotechnology; Biophysics; Cell and Molecular Biology; Biophysical Chemistry; Interfaces; Self-Assembly; Thermodynamics (Physical Chem.) | CC BY NC ND 4.0 | CHEMRXIV | 2021-04-12 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/60c75761337d6c782ae29004/original/influence-of-different-polymer-belts-on-lipid-properties-in-nanodiscs-characterized-by-cw-epr-spectroscopy.pdf |
64f75229dd1a73847f3f28b6 | 10.26434/chemrxiv-2023-h8b9n | Machine learning-based peptide-spectrum match rescoring opens up the immunopeptidome | Immunopeptidomics is a key technology in the discovery of targets for immunotherapy and vaccine development. However, identifying immunopeptides remains challenging due to their non-tryptic nature, which results in distinct spectral characteristics. Moreover, the absence of strict digestion rules leads to extensive search spaces, further amplified by the incorporation of somatic mutations, pathogen genomes, unannotated open reading frames, and post-translational modifications. This inflation in search space leads to an increase in random high-scoring matches, resulting in fewer identifications at a given false discovery rate. Peptide-spectrum match rescoring has emerged as a machine learning-based solution to address challenges in mass spectrometry-based immunopeptidomics data analysis. It involves post-processing unfiltered spectrum annotations to better distinguish between correct and incorrect peptide-spectrum matches. Recently, features based on predicted peptidoform properties, including fragment ion intensities, retention time, and collisional cross section, have been used to improve the accuracy and sensitivity of immunopeptide identification. In this review, we describe the diverse bioinformatics pipelines that are currently available for peptide-spectrum match rescoring and discuss how they can be used for the analysis of immunopeptidomics data. Finally, we provide insights into current and future machine learning solutions to boost immunopeptide identification. | Charlotte Adams; Kris Laukens; Wout Bittremieux; Kurt Boonen | Theoretical and Computational Chemistry; Biological and Medicinal Chemistry; Analytical Chemistry; Mass Spectrometry; Bioinformatics and Computational Biology; Machine Learning | CC BY 4.0 | CHEMRXIV | 2023-09-06 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/64f75229dd1a73847f3f28b6/original/machine-learning-based-peptide-spectrum-match-rescoring-opens-up-the-immunopeptidome.pdf |
65f637829138d231619d21f6 | 10.26434/chemrxiv-2023-x8vxb-v2 | Liquid-Liquid Transition and Ice Crystallization in a Machine-Learned Coarse grained Water Model | Mounting experimental evidence supports the existence of a liquid-liquid transition (LLT) in high-pressure supercooled water. However, fast crystallization of supercooled water has impeded identification of the LLT line TLL(p) in experiments. While the most accurate all-atom (AA) water models display a LLT, their computational cost limits investigations of its interplay with ice formation. Coarse-grained (CG) models provide over 100-fold computational efficiency gain over AA models, enabling the study of water crystallization, but have not yet shown to have a LLT. Here we demonstrate that the CG machine-learned water model ML-BOP has a LLT that ends in a critical point at pc = 170±10 MPa and Tc = 181±3 K. The TLL(p) of ML-BOP is almost identical to the one of TIP4P/2005, adding to the similarity in the equation of state of liquid water in both models. Cooling simulations reveal that ice crystallization is fastest at the liquid-liquid transition and its supercritical continuation of maximum heat capacity, supporting a mechanistic relationship between the structural transformation of water to a low-density liquid and ice formation. We find no signature of liquid-liquid criticality in the ice crystallization temperatures. ML-BOP repli-cates the competition between formation of low-density liquid (LDL) and ice observed in ultrafast experiments of decompres-sion of the high-density liquid (HDL) into the region of stability of LDL. The simulations reveal that crystallization occurs prior to the coarsening of the HDL and LDL domains, obscuring the distinction between the highly metastable first order LLT and pronounced structural fluctuations along its supercritical continuation. | Debdas Dhabal; Rajat Kumar; Valeria Molinero | Theoretical and Computational Chemistry; Physical Chemistry; Theory - Computational; Thermodynamics (Physical Chem.) | CC BY NC ND 4.0 | CHEMRXIV | 2024-03-18 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/65f637829138d231619d21f6/original/liquid-liquid-transition-and-ice-crystallization-in-a-machine-learned-coarse-grained-water-model.pdf |
60c74b9d4c89191290ad34be | 10.26434/chemrxiv.12363069.v1 | Aggregation Induced Emission in the Tetraphenylthiophene Crystal: The Role of Triplet States | <p>Propeller-shaped molecules have received much attention due to their enhanced emission in the condensed phase (Aggregation Induced Emission, AIE) and their potential use in optoelectronic devices. In this contribution, we examine the excited state mechanisms of tetraphenyl-thiophene (TPT), one member of the family which features weaker AIE. We perform a detailed analysis of the potential energy surfaces with special focus on the role of triplet states considering the crystal structure, intermolecular interactions, exciton couplings and reorganisation energies in the vacuum and solid state. In contrast with other members of the propeller-shaped family, nonradiative decay in TPT is driven by bond breaking. Because of the significant spin-orbit couplings along the reaction coordinate, intersystem crossing plays an important role in the mechanism. Our calculations show that aggregation in the solid state hampers the access to internal conversion pathways, however, intersystem crossing is active in the crystal phase, which explains the weak AIE of this molecule. This new understanding of the role of triplet states on the relaxation mechanisms of AIEgens has implications for the design of solid state highly-emissive materials based on TPT.<br /></p> | Ljiljana Stojanovic; Rachel Crespo Otero | Computational Chemistry and Modeling; Photochemistry (Physical Chem.) | CC BY NC ND 4.0 | CHEMRXIV | 2020-05-26 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/60c74b9d4c89191290ad34be/original/aggregation-induced-emission-in-the-tetraphenylthiophene-crystal-the-role-of-triplet-states.pdf |
676078fd81d2151a02f75059 | 10.26434/chemrxiv-2024-0m10m | Implementing recyclable bio- and CO2-sourced synergetic dynamic matrices via precise control of curing and properties for natural fiber composites within industrially relevant resin transfer molding | Natural Fiber Composites (NFCs) offer significant environmental benefits. However, the use of thermoset matrices presents major challenges since they are oil-based, non-recyclable, and require energy-intensive curing processes, which diminishes their sustainability. Various proposed alternatives, particularly sustainable, dynamic matrices, have limited industrial applicability as they often lack the appropriate curing kinetics and viscosity needed for conventional composite processing techniques, such as Resin Transfer Molding (RTM). CO2-derived polyhydroxyurethanes (PHUs) show promise as NFC matrices but are hampered by poor processability and complex workup procedures, confining them mainly to laboratory settings. This study explores a synergetic copolymerization strategy that combines epoxy and PHU to allow fine-tuned polymerization kinetics and, thus, suitability for the RTM process. We demonstrate a synergetic catalytic effect that accelerates curing compared to each neat component. The formulation maintains a low viscosity (<5 Pa.s) at room temperature while curing within 30 minutes at 80°C—unattainable conditions with pure PHUs. The RTM-made composite achieves a fiber volume fraction of 58-60% and a porosity below 1%, making it ideal for high-quality NFCs. Moreover, the catalyst-free dynamic matrix allows the reshaping after curing, and flax fibers can be easily separated without toxic reagents from the polymer under mild conditions (60°C for 2 hours) and reused, retaining properties similar to those of virgin yarns. This strategy could broaden the application of PHU chemistry in sustainable NFC manufacturing while preserving both natural and fossil feedstock. | Guillem Seychal; Bernard Miranda Campos; Gabriel Perli; Vincent Placet; Bruno Grignard; Fanny Bonnet; Christophe Detrembleur; Haritz Sardon; Nora Aranburu; Jean-Marie Raquez | Materials Science; Polymer Science; Composites; Materials Processing; Cellulosic materials | CC BY NC ND 4.0 | CHEMRXIV | 2024-12-19 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/676078fd81d2151a02f75059/original/implementing-recyclable-bio-and-co2-sourced-synergetic-dynamic-matrices-via-precise-control-of-curing-and-properties-for-natural-fiber-composites-within-industrially-relevant-resin-transfer-molding.pdf |
66ed8b2951558a15ef948e5e | 10.26434/chemrxiv-2024-rk8q2-v2 | Mycobacterium tuberculosis Mce3R TetR-like Repressor Forms an Asymmetric Four-Helix Bundle and Binds a Non-Palindrome Sequence | Mycobacterium tuberculosis (Mtb), the causative agent of tuberculosis, is a major global health concern. TetR family repressors (TFRs) are important for Mtb's adaptation to the human host environment. Our study focuses on one notable Mtb repressor, Mce3R, composed of an unusual double TFR motif. Mce3R-regulated genes encode enzymes implicated in cholesterol metabolism, resistance against reactive oxygen species, lipid transport activities important for Mtb survival and persistence in the host, and for the cellular activity of a 6-azasteroid derivative. Here, we present the structure of Mce3R bound to its DNA operator, unveiling a unique asymmetric assembly previously unreported. We obtained a candidate DNA binding motif through MEME motif analysis, comparing intergenic regions of mce3R orthologues and identifying non-palindromic regions conserved between orthologues. Using an electrophoretic mobility shift assay (EMSA), we confirmed that Mce3R binds to a 123 bp sequence that includes the predicted motif. Using scrambled DNA and DNA oligonucleotides of varying lengths with sequences from the upstream region of the yrbE3A (mce3) operon, we elucidated the operator region to be composed of two Mce3R binding sites, each a 25 bp asymmetric sequence separated by 53 bp. Mce3R binds with higher affinity to the downstream site with a Kd of 2.4 ± 0.7 nM. The cryo-EM structure of Mce3R bound to the 123 bp sequence was refined to a resolution of 2.51 Å. Each Mce3R monomer comprises 21 α-helices (α1-α21) folded into an asymmetric TFR-like structure with a core asymmetric four-helix bundle. This complex has two non-identical HTH motifs and a single ligand-binding domain. The two non-identical HTHs from each TFR bind within the high-affinity, non-palindromic operator motif, with Arg53 and Lys262 inserted into the major groove. Site-directed mutagenesis of Arg53 to alanine abrogated DNA binding, validating the Mce3R/DNA structure obtained. Among 811,645 particles, 63% were Mce3R homodimer bound to two duplex oligonucleotides. Mce3R homodimerizes primarily through α15, and each monomer binds to an identical site in the DNA duplex oligonucleotide. | Navanjalee T. Panagoda ; Gábor Balázsi; Nicole S. Sampson | Biological and Medicinal Chemistry; Biochemistry; Chemical Biology; Microbiology | CC BY NC ND 4.0 | CHEMRXIV | 2024-09-23 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/66ed8b2951558a15ef948e5e/original/mycobacterium-tuberculosis-mce3r-tet-r-like-repressor-forms-an-asymmetric-four-helix-bundle-and-binds-a-non-palindrome-sequence.pdf |
65d1eae79138d2316161bd85 | 10.26434/chemrxiv-2024-4hksp | Cu(I)-Catalyzed Atropselective Heterobiaryl Coupling Employing Umpoled Indoles | Despite significant advances in the C-H/C-H coupling for the synthesis of axially chiral indolylaryl compounds, control over chemo-, regio-, and atropselectivity remains a significant challenge. We introduce herein N-carboxyindoles as an electrophilic partner that couple with a range of 2-naphthols and phenols in a highly chemo- and enantioselective manner (up to 96:4 er). Deuterium exchange and in-situ 1H NMR spectroscopy supports that the chirality is generated and transferred via dearomatized naphthol intermediates. Experiments with radical clocks, radical inhibitors and DFT computation suggested an outer-sphere attack of N-carboxyindole on Cu-bound naphthols, rather than through ligated naphthoxyl radical intermediates. | Nguyen H. Nguyen; Sanghyup Seo; Jiwon Jang; Hyunwoo Kim; Seunghoon Shin | Organic Chemistry; Organic Synthesis and Reactions | CC BY 4.0 | CHEMRXIV | 2024-02-23 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/65d1eae79138d2316161bd85/original/cu-i-catalyzed-atropselective-heterobiaryl-coupling-employing-umpoled-indoles.pdf |
61da007d828c2f6afcdc42be | 10.26434/chemrxiv-2022-12b8g-v3 | Abiotic Reactivity of De Novo Designed Artificial Copper Peptides (ArCuPs): The Case of C-H Activation | We report a series of de novo designed Artificial Cu Peptides (ArCuPs) that oxidize and peroxygenate C-H bonds of model abiotic substrates via electrochemically generated Cu-oxygen species using H2O2 as the terminal oxidant, akin to native Cu enzymes. Detailed assessment of kinetic parameters established the catalytic nature of the ArCuPs. Selective alteration of outer sphere steric at the d layers above and below the Cu site allows facilitated access of substrates, where a more pronounced effect on catalysis is observed when space is created at the d layer below the Cu site via Ile to Ala mutation producing a kcat of 6.2 s-1, TONmax of 14800 and catalytic proficiency (kcat/KM/kuncat) of 340 M-1 for the oxidation of benzyl alcohol. Independent spectroscopic studied revealed that the rate of formation of the Cu-oxygen species and the spectroscopic feature of the most active variant is distinct compared to the other ArCuPs. Systematic alteration of outer sphere hydrophobicity led to a correlated tuning of the T2 Cu site redox potentials by ~80 mV. The enhanced activity of the ArCuP variant is attributed to a combination of steric effect that allows easy access of substrates, the nature of Cu-oxygen species, and stability of this construct compared to others, where Ile to Ala mutation unexpectedly leads to a higher thermostability which is further augmented by Cu binding. | Divyansh Prakash; Suchitra Mitra; Morgan Murphy; Saumen Chakraborty | Inorganic Chemistry; Catalysis; Energy; Bioinorganic Chemistry; Small Molecule Activation (Inorg.); Biocatalysis | CC BY NC ND 4.0 | CHEMRXIV | 2022-01-10 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/61da007d828c2f6afcdc42be/original/abiotic-reactivity-of-de-novo-designed-artificial-copper-peptides-ar-cu-ps-the-case-of-c-h-activation.pdf |
60c75154bdbb8949dca3a09d | 10.26434/chemrxiv.12966725.v2 | Polymer Microarrays Rapidly Identify Competitive Adsorbents of Virus-like Particles (VLPs) | <p>The emergence of SARS-CoV-2 highlights the global need for platform technologies to enable rapid development of diagnostics, vaccines, treatments, and personal protective equipment (PPE). However, many current technologies require the detailed mechanistic knowledge of specific material-virion interactions before they can be employed, for example to aid in the purification of vaccine components, or in design of more effective PPE. Here we show that an adaption of polymer micro array method for screening bacterial-surface interactions allows for screening of polymers for desirable material-viron interactions. Non-pathogenic <i>virus like particles</i>including fluorophores are exposed to the arrays in aqueous buffer as a simple model of virons carried to the surface in saliva/sputum. Competitive binding of Lassa and Rubella particles is measured to probe the relative binding properties of a selection of copolymers. This provides the first step in the development of a method for discovery of novel materials with promise for viral binding, with the next being development of this method to assess absolute viral adsorption and assessment of the attenuation of the activity of live virus which we propose would be part of a material scale up step carried out in biological laboratory safety level 4 facilities and the use of more complex media to represent biological fluids.</p><p></p> | Andrew J. Blok; Pratik Gurnani; Alex Xenopoulos; Laurence Burroughs; Joshua Duncan; Richard Urbanowicz; Theocharis Tsoleridis; Helena Müller; Thomas Strecker; Jonathan Ball; Cameron Alexander; Morgan Alexander | Bioengineering and Biotechnology | CC BY NC 4.0 | CHEMRXIV | 2020-10-21 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/60c75154bdbb8949dca3a09d/original/polymer-microarrays-rapidly-identify-competitive-adsorbents-of-virus-like-particles-vl-ps.pdf |
67a125dd81d2151a0212bcc4 | 10.26434/chemrxiv-2025-vxgll | Designing reversible photoswitching azobenzene modified nucleotide for controlling biological function | RNA plays vital roles in numerous normal and diseased cellular functions and processes. Reversible photoregulation of oligonucleotide’s structure and function is a powerful strategy for both regulating biological processes and developing novel RNA-based therapeutics. Here, we designed an azobenzene modified cytidine phosphoramidite and synthesized a series of RNA oligonucleotides containing this photoswitchable residue. We validated the reversible photoisomerization in both nucleoside and oligonucleotide contexts, and studied the overall impact of this cytidine modification through all-atom molecular dynamics (MD) simulations and UV melting experiments. We also showed that the modified oligonucleotide can switch reverse transcription (RT) process upon light irradiation in the presence of various RT enzymes. In addition, the optical control mechanism of HIV reverse transcriptase mediated RT process was elucidated by MD simulation. This new chemical biology toolset enables reversible optical control of RNA structures and functions for gene regulation and novel drug development. | Juncheng Li; Jinxi Du; Weiwei He; Ibrahim Adelakun; Miao Zhong; Savia Boyer; Ya Ying Zheng; Qishan Lin; Serdal Kirmizialtin; Jia Sheng; Ting Wang | Biological and Medicinal Chemistry; Organic Chemistry; Bioorganic Chemistry; Chemical Biology | CC BY NC ND 4.0 | CHEMRXIV | 2025-02-05 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/67a125dd81d2151a0212bcc4/original/designing-reversible-photoswitching-azobenzene-modified-nucleotide-for-controlling-biological-function.pdf |
60c74db90f50db80a03970c5 | 10.26434/chemrxiv.12654536.v1 | Perovskite Oxides as Electrocatalyst for Glycerol Oxidation. | Glycerol is a co-product from Biodiesel production with high abundance and low market price. Its transformation into valuable products or as an alternative source of energy has driven the search for selective catalysts. Herein we present the first findings of perovskites as electrocatalysts for glycerol electrooxidation (GEOR). Alternatively to Pt and Pd based catalyst, perovskite oxides (LaNiO<sub>3</sub> and LaCoO<sub>3</sub>) demonstrated high catalytic performance with faradaic currents of ca. 18 mA mg<sup>-1</sup> at potentials higher than 1.6 V vs. RHE. Consecutive potential cycles exhibited the LaCoO<sub>3</sub> perovskite resistant to poisoning during GEOR. Based on FTIR and online HPLC experiments the GEOR on perovskite oxides yields formic acid and glycolic acid as final products, with no signal of CO<sub>2</sub> formation. Our results thus indicate that perovskites can be considered as an alternative for selectively oxidize glycerol, opening the door for a large variety of a new class of catalysts for polyols oxidation with efficiency in terms of current densities and poisoning stability. | Patrícia Santiago; Carlos C. Lima; José L. Bott-Neto; Pablo Fernández; Camilo A. Angelucci; Janaina Souza-Garcia | Electrochemistry - Mechanisms, Theory & Study | CC BY NC ND 4.0 | CHEMRXIV | 2020-07-15 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/60c74db90f50db80a03970c5/original/perovskite-oxides-as-electrocatalyst-for-glycerol-oxidation.pdf |
60c7508e9abda23668f8da6f | 10.26434/chemrxiv.13055522.v1 | Coupling of Alternating Current to Transition-Metal Catalysis: Examples of Nickel-Catalyzed Cross-Coupling | This work demonstrates that periodic oxidation and
reduction of a catalyst by alternating current enable otherwise unfavorable
catalytic cycles. Nickel catalyzed amination, etherification, and
esterification were universally enabled by alternating current with yields and
selectivity strongly exciding these in the experiments with direct current
(DC). | Evgeniy Bortnikov; Sergey Semenov | Electrocatalysis; Homogeneous Catalysis; Redox Catalysis | CC BY NC ND 4.0 | CHEMRXIV | 2020-10-06 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/60c7508e9abda23668f8da6f/original/coupling-of-alternating-current-to-transition-metal-catalysis-examples-of-nickel-catalyzed-cross-coupling.pdf |
674dd654f9980725cfcbbd56 | 10.26434/chemrxiv-2024-xkt1j-v2 | Machine learning prediction of the most intense peak
of the absorption spectra of organic molecules
| Accurate knowledge of electronic molecular properties of excited states is fundamental for understanding the behavior of functional materials for organic electronics and sensors. In this work, we focus on determining the properties of the most intense peak in the electronic absorption spectra of organic molecules. For this purpose, we employed the quantum chemistry QM-symex dataset, which has approximately 173,000 organic molecules and time-dependent DFT (TD-DFT) data of the first ten electronic absorption transitions. Each one is identified by its Cartesian coordinates. From data in the original QM-symex, we built a new dataset named QM-symex-modif that contains molecules in Simplified Molecular Input Line Entry System (SMILES) format and properties related to the main electronic transition. We then employed twenty machine learning (ML) algorithms to investigate oscillator strengths, excitation energies, transition orbitals, and the highest occupied molecular orbitals (HOMOs). As inputs for the ML algorithms, we used several chemical descriptors for each molecule generated in the RDKit tool employing the corresponding SMILES format. The generated input descriptors significantly improved the accuracy of the ML predictions for these key photophysical properties. Very good mean absolute errors (MAEs) were obtained for the test set composed of 45,056 molecules, namely, an MAE of 0.035 for oscillator strengths, 0.09 eV for excitation energies, 1.24 and 0.62 for the initial and final transition molecular orbital (MO) numbers (i.e., for each molecule, their position in the MO listing) respectively, and 0.014 for HOMO numbers, with R² values consistently exceeding 0.94, thus demonstrating the accuracy of the models. Additionally, a Shapley additive explanation (SHAP) analysis was carried out to evaluate the importance of the input parameters for the investigated ML models. We found several interesting relationships involving the input parameters. In particular, molecular weight holds significant importance in our ML models for determining the target HOMO numbers and the transition orbitals. | Rubens Souza; Julio Duarte; Ronaldo Goldschmidt; Itamar Borges Jr | Theoretical and Computational Chemistry; Materials Science; Computational Chemistry and Modeling; Machine Learning; Chemoinformatics - Computational Chemistry | CC BY NC ND 4.0 | CHEMRXIV | 2024-12-03 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/674dd654f9980725cfcbbd56/original/machine-learning-prediction-of-the-most-intense-peak-of-the-absorption-spectra-of-organic-molecules.pdf |
670d348fcec5d6c1421ef3d1 | 10.26434/chemrxiv-2024-rrp4p | Batch and continuous synthesis of 5,5-diphenylhydantoin, an active pharmaceutical ingredient | A teaching laboratory protocol was developed for the implementation of an ultrasound-assisted continuous-flow synthesis of 5,5-diphenylhydantoin, a drug used for epilepsy and tonic-clonic seizures. This methodology allowed students to understand concepts of green chemistry, ultrasound irradiation, continuous flow chemistry and drug synthesis. | Filipa Siopa; Maria Perry; Ana P. Francisco,; Carlos Afonso | Organic Chemistry; Chemical Education; Organic Synthesis and Reactions | CC BY NC ND 4.0 | CHEMRXIV | 2024-10-16 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/670d348fcec5d6c1421ef3d1/original/batch-and-continuous-synthesis-of-5-5-diphenylhydantoin-an-active-pharmaceutical-ingredient.pdf |
634ee7d9de2a219c90aa6a71 | 10.26434/chemrxiv-2022-d9qxx | Fluorescent Dissolved Organic Matter Constituents as Surrogates for Disinfection Byproduct Formation in Drinking Water Treatment: A Critical Review | Disinfection byproduct (DBP) formation, prediction and minimization are a crucial issue for the domestic water supply industry, which needs to provide quality and safe drinking water to consumers. Fluorescence excitation−emission matrices-parallel factor analysis (EEM-PARAFAC), is used to characterize and quantify fluorescent dissolved organic matter (DOM) in aquatic systems. EEM-PARAFAC has been identified as a potential method to predict DBP formation in treated waters. However, the method ability for specific DBP classes or species prediction is uncertain. This critical review evaluates the published literature describing empirical relationships between DOM fluorophores identified by PARAFAC components and DBP formation obtained during water disinfection. From 42 selected peer-reviewed articles, 202 established linear relationships (R2 ≥0.5) with DBP classes or species were found. Trihalomethanes (THMs) and haloacetic acids (HAAs), as regulated compounds, were extensively investigated and exhibit a strong relationship. Overall, carbonaceous-DBP classes exhibited strong relationships with humic/fulvic-like components. Conversely, a relationship between nitrogenous-DBP classes and PARAFAC components was less clear, but it was shown to be preferential to protein-like PARAFAC components in the case of algae/bacterial DOM sources. This review highlights the challenges of transposing site-specific or DOM source-specific empirical relationship between PARAFAC component and DBPs formation potential to a global model. | Elena Fernandez-Pascual; Boris Droz; Jean O'Dwyer; Connie O'Driscoll; Emma Goslan; Simon Harrison; John Weatherill | Analytical Chemistry; Earth, Space, and Environmental Chemistry; Hydrology and Water Chemistry; Chemoinformatics; Environmental Analysis | CC BY NC ND 4.0 | CHEMRXIV | 2022-10-20 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/634ee7d9de2a219c90aa6a71/original/fluorescent-dissolved-organic-matter-constituents-as-surrogates-for-disinfection-byproduct-formation-in-drinking-water-treatment-a-critical-review.pdf |
60c749ee702a9b676318b1e8 | 10.26434/chemrxiv.12117558.v1 | Copper(II) and Zinc(II) Complexes of Mono- and Bis-1,2,3-Triazolesubstituted Heterocyclic Ligands | Chelating 1,4-disubstituted mono- (8a−8d) and bis-1,2,3-triazole-based (9a−11a) ligands were prepared by regioselective copper(I)-catalysed 1,3-dipolar cycloaddition of terminal alkynes with aromatic azides, together with bioconjugate 13a synthesized by amide coupling of L-phenylalanine methyl ester to 11a. Cu(II) and Zn(II) complexes were prepared and single crystal structures were determined for complexes 8aCu, 8dCu, 9cCu and 10cCu, as well as the free ligands 10a and 10c. The in situ prepared Zn(II) complexes were studied by NMR spectroscopy, while the stoichiometry of the Cu(II) complexes in solution was determined by UV-Vis titrations and confirmed by the electronic structure DFT calculations at the (SMD)/M05-2X/6-31+G(d)/LanL2DZ + ECP level of theory. | Natalija Pantalon Juraj; Marko Krklec; Tiana Novosel; Berislav Perić; Robert Vianello; Silvana Raić-Malić; Srećko Kirin | Bioinorganic Chemistry; Supramolecular Chemistry (Inorg.); Crystallography – Inorganic | CC BY NC ND 4.0 | CHEMRXIV | 2020-04-17 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/60c749ee702a9b676318b1e8/original/copper-ii-and-zinc-ii-complexes-of-mono-and-bis-1-2-3-triazolesubstituted-heterocyclic-ligands.pdf |
60c741eb702a9ba69818a35e | 10.26434/chemrxiv.8182088.v1 | Ultrastrong, Free-Standing and Large Nanofilms of Pyrenearamid | We introduce poly(1,6-pyrene terephthalamide) polymer (PPyrTA) as an aromatic polyamide analogue of poly(p-phenylene terephthalamide) (PPTA), also known as Kevlar®. This work shows that the incorporation of polycyclic aromatic pyrene moieties improves drastically the mechanical properties of the polymeric structure, increasing elastic nanoindentation-determined modulus and hardness by factors of 1.9 and 4.3, respectively. Liquid deprotonated dispersions of PPyrTA nanofibers were used as nanoscale building block for producing large-surface, free-standing polymer macroscopic nanofilms. This 2D assembly leads to further significant improvements in reduced modulus and hardness (more than twice) compared to the starting polymer macroscale fibres, due to a better re-organizational arrangement of the PPyrTA nanofibers in the nanofilms, formed under 2D spatial confinement. | Amalia Rapakousiou; Alejandro López-moreno; Belén Nieto-Ortega; M. Mar Bernal; Miguel A. Monclús; Santiago Casado; Cristina Navío; Luisa R. González; Juan P. Fernández-Blázquez; Juan J. Vilatela; Emilio Pérez | Nanostructured Materials - Materials; Nanostructured Materials - Nanoscience; Polymers | CC BY NC ND 4.0 | CHEMRXIV | 2019-05-28 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/60c741eb702a9ba69818a35e/original/ultrastrong-free-standing-and-large-nanofilms-of-pyrenearamid.pdf |
61093a157bf0c95fd4629f12 | 10.26434/chemrxiv-2021-z299p-v3 | The Effect of Particle Size on the Optical and Electronic Properties of MgO Nanoparticles | The quasiparticle states, fundamental gaps, optical gaps, exciton binding energies and UV-Vis spectra for a series of cuboidal nanoparticles of the prototypical oxide magnesium oxide (MgO), the largest of which has 216 atoms and edges of 1 nm, were predicted using many-body perturbation theory (evGW-BSE). The evolution of the properties with particle size was explicitly studied. It was found that while the highest occupied and lowest unoccupied quasiparticle states and fundamental gap change with particle size, the optical gap remains essentially fixed for all but the smallest nanoparticles, in line with what was previously observed experimentally. The explanation for these observations is demonstrated to be that while the optical gap is associated with an exciton that is highly localised around the particle’s corner atoms, the highest occupied and lowest unoccupied quasiparticle states, while primarily localised on the oxygen corner atoms (hole) and magnesium corner atoms -(electron), show significant delocalisation along the edges. The strong localisation of the exciton associated with the optical gap on the corner atoms is argued to also explain why the nanoparticles have a much smaller optical gaps and red-shifted spectra than bulk MgO. Finally, it is discussed how this non-quantum confinement behaviour, where the properties of the nanoparticles arise from surface defects rather than differences in localisation of edge or exciton states, appears typical of alkaline earth oxide nanoparticles, and that the true optical gap of bulk crystals of such materials is also probably the result of surface defects, even if unobservable experimentally. | Martijn Zwijnenburg | Theoretical and Computational Chemistry; Physical Chemistry; Nanoscience; Nanostructured Materials - Nanoscience; Clusters; Quasiparticles and Excitations | CC BY NC ND 4.0 | CHEMRXIV | 2021-08-04 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/61093a157bf0c95fd4629f12/original/the-effect-of-particle-size-on-the-optical-and-electronic-properties-of-mg-o-nanoparticles.pdf |
63a18f1304902a637f09c684 | 10.26434/chemrxiv-2022-9cq8q | trans-Haloboration of o-Alkynyl Phenols Generates Halogenated Bicyclic-Boronates Relevant to Broad Spectrum Beta-Lactamase Inhibitors | Benzoxaborinines are key intermediates on route to bicyclic boronates that are ultra-broad spectrum beta-lactamase inhibitors (BLIs). However, routes to benzoxaborinines are limited and substituents at C4 are not tolerated in the current key method. Herein, the haloboration of o-alkynyl-phenols using BX3 (X = Cl or Br) is disclosed as a simple route to form C4-halogenated benzoxaborinines. The functional group tolerance is excellent for an electrophilic borylation process, tolerating halides, ethers, esters, CF3 and an enolisable ketone. This methodology was extended to form benzoxaborinines with an ester at the C8 posi-tion (key for accessing highly active BLIs) in high yield by using BCl3 and [BCl4]−. The requirement for [BCl4]− as an exogenous chloride source indicated a switch in the haloboration mechanism and computational studies indicated that there are two similar in barrier mechanisms: (i) double alkyne haloboration followed by a retro-haloboration; (ii) concerted alkyne trans-haloboration with an exogenous chloride source ([BCl4]−). The C4-halide unit in these benzoxaborinines is useful, with a haloboration-Negishi cross coupling protocol used to form benzoxaborinines with an alkyl or an aryl group at C4. This simple trans-haloboration methodology represents a useful addition to the chemists toolbox for synthesizing bicyclic-boronates that are in-creasingly important active pharmaceutical ingredients. | Kang Yuan; Michael Ingleson | Organic Chemistry; Organic Compounds and Functional Groups; Organic Synthesis and Reactions | CC BY 4.0 | CHEMRXIV | 2022-12-21 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/63a18f1304902a637f09c684/original/trans-haloboration-of-o-alkynyl-phenols-generates-halogenated-bicyclic-boronates-relevant-to-broad-spectrum-beta-lactamase-inhibitors.pdf |
63f330899da0bc6b333d2812 | 10.26434/chemrxiv-2023-h9qdj | Physics-Inspired Machine Learning of Localized Intensive Properties | Machine learning (ML) has been widely applied to chemical property prediction, most prominently for the energies and forces in molecules and materials. The strong interest in predicting energies in particular has led to a local energy-based paradigm for modern atomistic ML models, which ensures size-extensivity and a linear scaling of computational cost with system size. However, many electronic properties (such as excitation energies or ionization energies) do not necessarily scale linearly with system size and may even be spatially localized. Using size-extensive models in these cases can lead to large errors. In this work, we explore different strategies for learning intensive and localized properties, using HOMO energies in organic molecules as a representative test case. In particular, we analyze the pooling functions that atomistic neural networks use to predict molecular properties, and suggest an orbital weighted average (OWA) approach that enables the accurate prediction of orbital energies and locations. | Ke Chen; Christian Kunkel; Bingqing Cheng; Karsten Reuter; Johannes T. Margraf | Theoretical and Computational Chemistry; Machine Learning; Artificial Intelligence | CC BY NC 4.0 | CHEMRXIV | 2023-02-21 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/63f330899da0bc6b333d2812/original/physics-inspired-machine-learning-of-localized-intensive-properties.pdf |
6489d308e64f843f41c7c701 | 10.26434/chemrxiv-2023-n0zz0 | Oxidative Cross Dehydrogenative Coupling of N-Heterocycles with Aldehydes through C(sp3)–H Functionalization | Existing methodologies for metal-catalyzed cross-couplings typically rely on pre-installation of reactive functional groups on both reaction partners. In contrast, C–H functionalization approaches offer promise in simplification of the requisite substrates, however, challenges from low reactivity and similar reactivity of various CH bonds introduce considerable complexity. Herein, the oxidative cross dehydrogenative coupling of alpha-amino C(sp3)–H bonds and aldehydes to produce ketone derivatives is described using an unusual reaction medium that incorporates the simultaneous use of di-tert-butyl peroxide as an oxidant and zinc metal as a reductant. The method proceeds with a broad substrate scope, representing an attractive approach for accessing -amino ketones through the formal acylation of unactivated CH bonds in N-heterocycles. A combination of experimental investigation and computational modelling provides evidence for a mechanistic pathway involving cross-selective nickel-mediated cross-coupling of -amino radicals and acyl radicals. | Mo Chen; Austin Ventura; Soumik Das; Paul Zimmerman; John Montgomery | Theoretical and Computational Chemistry; Organic Chemistry; Catalysis; Organic Synthesis and Reactions; Homogeneous Catalysis; Redox Catalysis | CC BY 4.0 | CHEMRXIV | 2023-06-15 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/6489d308e64f843f41c7c701/original/oxidative-cross-dehydrogenative-coupling-of-n-heterocycles-with-aldehydes-through-c-sp3-h-functionalization.pdf |
66b62e3e5101a2ffa8b856c7 | 10.26434/chemrxiv-2024-1csmc-v2 | Annulation Producing Diverse Heterocycles Promoted by Cobalt Hydride | This study demonstrates the efficient synthesis of various heterocycles using the metal hydrogen atom transfer (MHAT)/ radical-polar crossover (RPC) method, emphasizing its versatility under mild conditions with high functional group tolerance. By distinguishing between cyclization and annulation, we underscore the complexity and efficiency of this approach in constructing intricate molecular architectures. Notably, the incorporation of an acetone solvent in the formation of cyclic acetal dioxanes from homoallylic alcohols reveals a novel annulation mechanism. Extensive substrate scope analysis and density functional theory calculations provide insights into reaction pathways, highlighting the critical role of cationic alkylcobalt(IV) intermediates and collidine in product selectivity. This study elucidates the mechanisms of the MHAT/RPC method and showcases its potential as a robust alternative to conventional synthetic strategies. | Takuma Sugimura; Ren Yamada; Wataru Kanna; Tsuyoshi Mita; Satoshi Maeda; Bartłomiej Szarłan; Hiroki Shigehisa | Organic Chemistry; Catalysis; Organometallic Chemistry; Organic Synthesis and Reactions; Catalysis; Reaction (Organomet.) | CC BY NC ND 4.0 | CHEMRXIV | 2024-08-12 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/66b62e3e5101a2ffa8b856c7/original/annulation-producing-diverse-heterocycles-promoted-by-cobalt-hydride.pdf |
60c743a3bdbb897083a3867f | 10.26434/chemrxiv.9365870.v1 | Highly Strained, Radially π-Conjugated Porphyrinylene Nanohoops | <p>Small
π conjugated nanohoops are difficult to prepare, but offer an excellent
platform for studying the interplay between strain and optoelectronic
properties and increasingly, these shape persistent macrocycles find uses in
host guest chemistry and self assembly. We report the synthesis of a new family
of radially π conjugated porphyrinylene/phenylene nanohoops. The strain energy
in the smallest nanohoop [2]CPT is approx-imately 54 kcal mol<sup>-1</sup>,
which results in a narrowed HOMO LUMO gap and a red shift in the visible part
of the absorption spectrum. Due to its high degree of preorganization and a
diameter of ca. 13 Å, [2]CPT was found to accommodate C<sub>60</sub> with a
binding affinity exceeding 10<sup>8</sup> M<sup>-1</sup> despite the fullerene
not fully entering the cavity of the host (X Ray crystallography). Moreover,
the π extended nanohoops [2]CPTN , [3]CPTN and [3]CPTA (N for 1,4 naphthyl; A
for 9,10 anthracenyl) have been prepared using the same strategy, and [2]CPTN
has been shown to bind C<sub>70</sub> five times more strongly than [2]CPT. Our
failed synthesis of [2]CPTA highlights a limitation of the experimental
approach most commonly used to prepare strained nanohoops, because in this
particular case the sum of aromatization energies no longer outweighs the
buildup of ring strain in the final reaction step (DFT calculations). These
results indicate that forcing ring strain onto organic semiconductors is a
viable strategy to fundamentally influence both optoelectronic and
supramolecular properties.</p> | Youzhi Xu; Sebastian Gsänger; Martin B. Minameyer; Inhar Imaz; Daniel Maspoch; Oleksandr Shyshov; Fabian Schwer; Xavi Ribas; Thomas Drewello; Bernd Meyer; Max von Delius | Supramolecular Chemistry (Org.) | CC BY NC ND 4.0 | CHEMRXIV | 2019-08-08 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/60c743a3bdbb897083a3867f/original/highly-strained-radially-conjugated-porphyrinylene-nanohoops.pdf |
65ef590fe9ebbb4db978de64 | 10.26434/chemrxiv-2024-plshq-v2 | Getting the intermolecular forces correct: introducing the ASTA strategy for a water model | Having a force field for water providing good bulk properties is paramount for modern studies of most biological systems. Some of the most common three-site force fields are TIP3, SPC/ϵ or OPC3, providing a decent range of bulk properties. That does not mean though, that they have realistic inter- atomic forces. These force fields have been parameterized with a top-down approach, meaning, by fitting the force field parameters to the experimental bulk properties. This approach has been the governing strategy also for many variants of four- and more-site models. We test a bottom- up approach, in which the force field is parameterized by optimizing the non-bonded inter-atomic forces. Our philosophy is that correct inter-atomic forces lead to correct geometrical and dynamical properties. The first system we try to optimize with the accurately system tailored atomic (ASTA) approach is water, but we aim to eventually probe other systems in the future as well. We applied our ASTA strategy to find a good set of parameters providing accurate bulk properties for the simple three-site force field forms, and also for AMOEBA, a more detailed and polarizable force field. Even though our bottom-up approach did not provide satisfactory results for the simple three-site force fields (with fixed charges), for the case of the AMOEBA force field it led to a modification of the original strategy, giving very good intra- and inter-molecular forces, as compared to accurate quantum chemically calculated reference forces. At the same time, important bulk properties, in this study restricted to the density and diffusion, were accurately reproduced with respect to the experimental values. | Jiří Mareš; Pau Mayorga Delgado | Theoretical and Computational Chemistry; Computational Chemistry and Modeling | CC BY NC ND 4.0 | CHEMRXIV | 2024-03-12 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/65ef590fe9ebbb4db978de64/original/getting-the-intermolecular-forces-correct-introducing-the-asta-strategy-for-a-water-model.pdf |
60c7432a0f50db31ac395e56 | 10.26434/chemrxiv.8947427.v1 | An In-Depth Mechanistic Study of Ru Catalysed Aqueous Methanol Dehydrogenation and Prospects for Future Catalyst Design | Herein we provide mechanistic insights into the dehydrogenation of aqueous methanol catalysed by the [Ru(trop<sub>2</sub>dae)] complex (which is in-situ generated from [Ru(trop<sub>2</sub>dad)]), established by density functional theory based molecular dynamics (DFT-MD) and static DFT calculations incorporating explicit solvent molecules. The aqueous solvent proved to participate actively in various stages of the catalytic cycle including the catalyst activation process, and the key reaction steps involving C-H activation and hydrogen production. The aqueous solvent forms an integral part of the reactive system for the C-H activation steps in the [Ru(trop<sub>2</sub>dae)] system, with strong hydrogen bond interactions with the anionic oxygen (RO<sup>-</sup>, R = CH<sub>3</sub>, CH<sub>2</sub>OH, HCO) and hydride moieties formed along the reaction pathway. In contrast to the [Ru(trop<sub>2</sub>dad)] catalyst, C-H activation and hydrogen production does not proceed via a metal-ligand cooperative pathway for the [Ru(trop<sub>2</sub>dae)] system. The pK<sub>a</sub> of the coordinated amine donors in these complexes provides a rationale for the divergent reactivity, and the obtained mechanistic information provides new guidelines for the rational design of active and additive free catalytic systems for aqueous methanol dehydrogenation.<br /> | Nitish Govindarajan; V. Sinha; Monica Trincado; Hansjörg Grützmacher; E.J. Meijer; Bas de Bruin | Computational Chemistry and Modeling; Homogeneous Catalysis | CC BY NC ND 4.0 | CHEMRXIV | 2019-07-18 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/60c7432a0f50db31ac395e56/original/an-in-depth-mechanistic-study-of-ru-catalysed-aqueous-methanol-dehydrogenation-and-prospects-for-future-catalyst-design.pdf |
60c74d33bb8c1a6caa3db573 | 10.26434/chemrxiv.12588479.v1 | Where Is the Unmatched Transition Metal in Substoichiometric Diboride Line Compounds? | <div>The atomic structure and local composition of high quality epitaxial substoichiometric titanium</div><div>diboride (TiB<sub>1.9</sub>) thin film, deposited by unbalanced magnetron sputtering, were studied using</div><div>analytical high-resolution scanning transmission electron microscopy, density functional theory</div><div>and image simulations. The unmatched Ti is pinpointed to planar defects on {1-100} prismatic</div><div>planes and attributed to the absence of B between Ti planes that locally relaxes the structure.</div><div>This mechanism allows the line compound to accommodate the off-stoichiometry and remain</div><div>a line compound between defects. The planar defects are embedded in otherwise stoichiometric</div><div>TiB<sub>2</sub> and are delineated by insertion of dislocations. An accompanied decrease in Ti-Ti bond</div><div>lengths along and across the faults is observed.</div><div>Introduction</div> | Justinas Palisaitis; Martin Dahlqvist; Allen J. Hall; Jimmy Thörnberg; Ingemar Persson; Nils Nedfors; Lars Hultman; Joseph E Greene; Ivan Petrov; Johanna Rosen; Per Persson | Alloys; Coating Materials; Thin Films | CC BY NC ND 4.0 | CHEMRXIV | 2020-07-03 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/60c74d33bb8c1a6caa3db573/original/where-is-the-unmatched-transition-metal-in-substoichiometric-diboride-line-compounds.pdf |
60c7441f842e65ab32db23bb | 10.26434/chemrxiv.9576644.v1 | Rationalizing the “Diels-Alderase” Activity of Pd2L4 Self-Assembled Metallocages: Enabling the Efficient Prediction of Catalytic Scaffolds | Self-assembled cages have emerged as novel platforms to explore bio-inspired catalysis. While many different size and shape supramolecular structures are now readily accessible, only a few are proficient catalysts. Here we show that a simple and efficient DFT-based methodology i is sufficient to accurately reproduce experimental binding affinities (MAD = 1.9 kcal mol-1) and identify the catalytic and non-catalytic Diels-Alder proficiencies (>90 % accuracy) of two homologous Pd2L4 metallocages with a variety of substrates. We demonstrate how subtle structural differences in the cage framework affect binding and catalysis, highlighting the critical role of structural dynamics and flexibility on catalytic activity. This flexibility manifests in a smaller transition state distortion energy for the catalytic cage compared to the inactive structure. To facilitate the computational exploration of novel Pd2L4 systems, we introduce an open-source Python module cgbind, which largely automates the screening of novel architectures. | Tom A. Young; Vicente Martí-Centelles; Jianzhu Wang; Paul J. Lusby; Fernanda Duarte | Supramolecular Chemistry (Org.); Computational Chemistry and Modeling | CC BY NC ND 4.0 | CHEMRXIV | 2019-08-30 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/60c7441f842e65ab32db23bb/original/rationalizing-the-diels-alderase-activity-of-pd2l4-self-assembled-metallocages-enabling-the-efficient-prediction-of-catalytic-scaffolds.pdf |
669ff44001103d79c5617f1d | 10.26434/chemrxiv-2024-6nl51-v3 | Uncovering Chemical Homology of Superheavy Elements: A Close Look at Astatine | The fascination with superheavy elements (SHE) spans the nuclear physics, astrophysics, and theoretical chemistry communities. Extreme relativistic effects govern these elements' chemistry and challenge the traditional notion of the periodic law. The experimental quest for SHE critically depends on theoretical predictions of these elements' properties, especially chemical homology, which allows for successful prototypical experiments with more readily available lighter homologs of SHE. This work is a comprehensive quantum-chemical investigation into astatine (At) as a non-intuitive homolog of element 113, nihonium (Nh). Combining relativistic coupled-cluster and density functional theory approaches, we model the behavior of At and AtOH in thermochromatographic experiments on a pristine gold surface. Insights into the electronic structure of AtOH and NhOH and accurate estimates of At–gold and AtOH–gold adsorption energies rationalize recent experimental findings and justify the use of At as a chemical homolog of Nh for the successful design of future experiments on Nh detection and chemical characterization. | Yuriy Demidov; Alexander Shalaevsky; Alexander Oleynichenko; Alexander Rusakov | Theoretical and Computational Chemistry; Computational Chemistry and Modeling; Theory - Computational | CC BY NC ND 4.0 | CHEMRXIV | 2024-07-25 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/669ff44001103d79c5617f1d/original/uncovering-chemical-homology-of-superheavy-elements-a-close-look-at-astatine.pdf |
63edd67f1d2d184063959d98 | 10.26434/chemrxiv-2023-r4480 | Visible Light Induced Catalyst-free Deaminative C-2 Alkylation of Heterocyclic-N-Oxides using Katritzky salts. | HEREIN, AN UNPRECEDENTED DIRECT C-2 ALKYLATION OF QUINOLINE-N-OXIDES WITH KATRITZKY SALTS VIA VISIBLE-LIGHT INDUCED CATALYST-FREE DEAMINATIVE APPROACH WAS DEVELOPED. MECHANISTIC STUDIES REVEALED THAT KATRITZKY SALTS AND BASE WERE INVOLVED TO GENERATE AN EDA COMPLEX, WHICH UNDERWENT INTERMOLECULAR SINGLE ELECTRON TRANSFER (SET) TO GIVE ALKYL RADICAL INTERMEDIATE. FINALLY, ALKYL RADICAL INTERMEDIATE FURTHER UNDERWENT-ADDITION WITH QUINOLINE-N-OXIDE SUBSTRATES TO ACCESS THE DESIRED ADDUCTS IN EXCELLENT YIELD. | Anuj Sharma; Nihal Singh; Shivani Sharma | Organic Chemistry; Organic Synthesis and Reactions | CC BY NC ND 4.0 | CHEMRXIV | 2023-02-17 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/63edd67f1d2d184063959d98/original/visible-light-induced-catalyst-free-deaminative-c-2-alkylation-of-heterocyclic-n-oxides-using-katritzky-salts.pdf |
672518847be152b1d0b15e6c | 10.26434/chemrxiv-2024-cqzpr-v2 | A review of methane emissions source types, characteristics, rates, and mitigation across U.S. and Canadian cities | Cities are major aggregate sources of methane (CH₄) emissions and play a critical role in mitigating near-term global temperature rise. However, characterizing urban CH₄ emissions remains challenging due to the diversity and spatial distribution of sources. Furthermore, limited synthesis and integration of the literature has led to a poor understanding of the characteristics and contributions of different sources, with implications for policies and mitigation. This review consolidates findings from 103 peer-reviewed articles on CH₄ emissions from cities in the U.S. and Canada, highlighting key research priorities. We find that top-down (TD) estimates of total city-level CH₄ emissions exceed bottom-up (BU) inventory estimates by a factor of 0.7 to 4.9 in 34 studies. In city-level studies that disambiguated emissions by source, natural gas distribution and use, and landfills, dominated urban CH₄ footprints. The mean natural gas loss rate in cities of 1.8% ± 0.9% suggests a broader natural gas supply chain loss rate of 4.0% ± 0.9%. Notably, TD estimates of CH₄ emissions from six select U.S. landfills were, on average, 2.6 (± 1.8) times greater than self-reported estimates, suggesting that preferred calculation methods for reporting may systematically underestimate emissions and miss fugitive point sources. A limited number of studies examined mitigation but indicate that measurement is essential to identify mitigation opportunities and verify reductions. We raise questions and highlight challenges around existing BU inventories, urban natural gas loss rates, combustion slip, landfill emissions estimation techniques, and mitigation effectiveness. We conclude with recommendations on research priorities to address key knowledge gaps: (i) new source-level measurement datasets and modeling approaches for BU emissions estimation; (ii) more granular investigations to understand the specific sources and causes of CH4 emissions from urban natural gas infrastructure and end use; (iii) a better coupling between measurement and modeling of landfill CH4 emissions; (iv) mitigation-focused studies. | Coleman Vollrath; Zhenyu Xing; Chris Hugenholtz; Thomas Barchyn; Jennifer Winter | Earth, Space, and Environmental Chemistry; Chemical Engineering and Industrial Chemistry; Atmospheric Chemistry; Environmental Science | CC BY 4.0 | CHEMRXIV | 2024-11-05 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/672518847be152b1d0b15e6c/original/a-review-of-methane-emissions-source-types-characteristics-rates-and-mitigation-across-u-s-and-canadian-cities.pdf |
62997986dd1809f936f3e0be | 10.26434/chemrxiv-2022-9ftjt | 2D HETCOR Solid-State NMR Spectroscopy for
Multiphase Materials with Mobility Contrast
| Two-dimensional heteronuclear chemical shift correlation experiments (HETCOR) under magic angle spinning (MAS) can provide the isotropic chemical shift and the proximity of different nuclei. The establishment of heteronuclear correlation is mainly achieved via cross polarization (CP) in solid samples, relying on the through-space dipolar couplings. As a result, such experiment typically suffers from severe limitations for the multiphase materials containing rigid and mobile components with significant mobility contrast, where the signals of mobile components in HETCOR spectra are often lost due to the efficient averaging of dipolar couplings by the fast molecular motions. Herein, we propose novel 1D and 2D HETCOR experiments, enabling sequential acquisition of 1D 13C and 2D HETCOR spectra of both rigid and mobile components in a single experiment, respectively. Particularly, CP and heteronuclear Overhauser effect is used for 1H13C polarization transfer in rigid and mobile components, respectively, both enabling achieving signal enhancement as well as remote heteronuclear chemical shift correlations. The proposed experiments were firstly demonstrated on the small molecular model system, glycine and adamantane mixture, and then on two typical polymer systems, including PMMA/PB blend (poly(methyl methacrylate)/polybutadiene) and PU (polyurethane). Due to the dynamic selectivity of this experiment, it can also be used for the fast chemical shift resonance assignment and dynamics based spectral editing of multiphase materials. We envisage that such an approach can be quite useful for the structural elucidation and thus revealing the interplay of structures and dynamics in multiphase materials. | Zhiwei Yan; Rongchun Zhang | Physical Chemistry; Spectroscopy (Physical Chem.) | CC BY NC ND 4.0 | CHEMRXIV | 2022-06-06 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/62997986dd1809f936f3e0be/original/2d-hetcor-solid-state-nmr-spectroscopy-for-multiphase-materials-with-mobility-contrast.pdf |
64362fa70784a63aeef63ac1 | 10.26434/chemrxiv-2022-lh8kl-v3 | Adaptive Language Model Training for Molecular Design | The vast size of chemical space necessitates computational approaches to automate and accelerate the design of molecular sequences to guide experimental efforts for drug discovery. Genetic algorithms provide a useful framework to incrementally generate molecules by applying mutations to known chemical structures. Recently, masked language models have been applied to automate the mutation process by leveraging large compound libraries to learn commonly occurring chemical sequences (i.e., using tokenization) and predict rearrangements (i.e., using mask prediction). Here, we consider how language models can be adapted to improve molecule generation for different optimization tasks. We use two different generation strategies for comparison, fixed and adaptive. The fixed strategy uses a pre-trained model to generate mutations; the adaptive strategy trains the language model on each new generation of molecules selected for target properties during optimization. Our results show that the adaptive strategy allows the language model to more closely fit the distribution of molecules in the population. Therefore, for enhanced fitness optimization, we suggest the use of the fixed strategy during an initial phase followed by the use of the adaptive strategy. We demonstrate the impact of adaptive training by searching for molecules that optimize both heuristic metrics, drug-likeness and synthesizability, as well as predicted protein binding affinity from a surrogate model. Our results show that the adaptive strategy provides a significant improvement in fitness optimization compared to the fixed pre-trained model, empowering the application of language models to molecular design tasks | Andrew Blanchard ; Debsindhu Bhowmik ; Zachary Fox ; John Gounley ; Jens Glaser ; Belinda S Akpa; Stephan Irle | Theoretical and Computational Chemistry; Biological and Medicinal Chemistry; Chemical Engineering and Industrial Chemistry; Bioinformatics and Computational Biology; Artificial Intelligence; Chemoinformatics - Computational Chemistry | CC BY NC ND 4.0 | CHEMRXIV | 2023-04-12 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/64362fa70784a63aeef63ac1/original/adaptive-language-model-training-for-molecular-design.pdf |
60c7488bbb8c1a05553dacb7 | 10.26434/chemrxiv.11920485.v1 | IDM-1, a New Zeolite with Intersecting Medium and Extra-Large Pores Built as an Expansion of Zeolite MFI | <p>
IDM-1
is a new silica zeolite with an ordered and well-defined framework
constructed by alternating pentasil layers and interrupted layers,
giving rise to an intersecting system of straight medium pores and
undulating extra-large lobed pores. This unique structure was solved
by rotation electron diffraction and refined against synchrotron
powder X-ray diffraction data. Despite the presence of both
Si(OSi)<sub>3</sub>(OH)
and Si(OSi)<sub>2</sub>(OH)<sub>2</sub>
sites, this new zeolite presents high thermal stability, withstanding
calcination even to 1000ºC. The location of defects at specific
sites of the structure results in alternating hydrophobic SiO<sub>2</sub>
and hydrophilic SiO<sub>(2-x)</sub>(OH)<sub>2x</sub>
intracrystalline regions. This peculiar combination of intersecting
medium and extra-large pores and alternating regions of different
chemical character may provide this zeolite with unique catalytic
properties.</p> | Luis Angel Villaescusa; Jian Li; Zihao Gao; Junliang Sun; Miguel Camblor | Catalysts | CC BY NC ND 4.0 | CHEMRXIV | 2020-03-03 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/60c7488bbb8c1a05553dacb7/original/idm-1-a-new-zeolite-with-intersecting-medium-and-extra-large-pores-built-as-an-expansion-of-zeolite-mfi.pdf |
6724fa397be152b1d0ae5ca6 | 10.26434/chemrxiv-2024-0b89h | Multi-Gram Scale Synthetic Routes to Solvent-Free Common Secondary Dialkylphosphines and Chlorodialkylphosphines | Secondary dialkylphosphines and chlorodialkylphosphines are some of the most common starting points in ligand synthesis, however sourcing these synthons can be troublesome. In this paper we present scalable synthetic routes to the iso-propyl, tert-butyl and cyclohexyl derivatives, starting either from PCl3 or HP(O)(OEt)2. Detailed experimental procedures are given to allow for ease of synthesis. | Amanda Fogh; Sara Belazregue; Andrew Ashley; Mark Chadwick | Inorganic Chemistry; Ligands (Inorg.) | CC BY NC ND 4.0 | CHEMRXIV | 2024-11-05 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/6724fa397be152b1d0ae5ca6/original/multi-gram-scale-synthetic-routes-to-solvent-free-common-secondary-dialkylphosphines-and-chlorodialkylphosphines.pdf |
66be517cf3f4b05290fa5645 | 10.26434/chemrxiv-2024-k11sz | OPEN DUMPING AND BURNING: AN OVERLOOKED SOURCE OF TERRESTRIAL MICROPLASTICS IN UNDERSERVED COMMUNITIES | Open dumping and burning of solid waste are widely practiced in underserved communities lacking access to solid waste management facilities; however, the generation of microplastics from these sites has been overlooked. We report elevated concentrations of microplastics (MPs) in soil of three solid waste open dump and burn sites: a single-family site in Tuttle, Oklahoma, USA, and two community-wide sites in Crow Agency and Lodge Grass, Montana, USA. We extracted, quantified, and characterized MPs from two soil depths (0-9 cm and 9-18 cm). The abundance of particles found at the three sites (35,000 to 69,200 particles kg-1 soil) equals or exceeds reported concentrations from currently understood sources of MPs including biosolids application and other agricultural practices. Attenuated total reflectance Fourier transformed infrared (ATR-FTIR) identified polyethylene as the dominant polymer across all sites (46.2%-84.8%). We also detected rayon (≤11.5%), polystyrene (up to 11.5%), polyethylene terephthalate (≤5.1), polyvinyl chloride (≤4.4%), polyester (≤3.1), and acrylic (≤2.2%). Burned MPs accounted for 76.3 to 96.9% of the MPs found in both community wide dumping sites. These results indicate that solid waste dumping and burning activities are a major source of thermally oxidized MPs for the surrounding terrestrial environment with potential to negatively affect underserved communities. | Kendra Z. Hess; Kyle Forsythe; Xuewen Wang; Gwen Tipling; Jesse Jones; Melissa Mata; Victoria Hughes; Christine Martin; John Doyle; Justin Scott; Matteo Minghetti; Andrea Jilling; Jose M. Cerrato; Eliane El Hayek; Jorge Gonzalez-Estrella | Earth, Space, and Environmental Chemistry; Environmental Science; Wastes | CC BY NC 4.0 | CHEMRXIV | 2024-08-22 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/66be517cf3f4b05290fa5645/original/open-dumping-and-burning-an-overlooked-source-of-terrestrial-microplastics-in-underserved-communities.pdf |
60c758434c89198600ad4b5e | 10.26434/chemrxiv.14529585.v1 | Equation-of-Motion Coupled-Cluster Protocol for Calculating Magnetic Properties: Theory and Applications to Single-Molecule Magnets | The manuscript presents our recent methodological developments that enable calculations of macroscopic magnetic properties within the equation-of-motion coupled-cluster (EOM-CC) framework. The methodology is illustrated by applications to transition-metal compounds (single-molecule magnets, SMMs). <br /> | Maristella Alessio; Anna Krylov | Theory - Computational | CC BY NC ND 4.0 | CHEMRXIV | 2021-05-05 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/60c758434c89198600ad4b5e/original/equation-of-motion-coupled-cluster-protocol-for-calculating-magnetic-properties-theory-and-applications-to-single-molecule-magnets.pdf |
677c0488fa469535b9fa119d | 10.26434/chemrxiv-2025-b3941 | Emerging concepts in immuno-oncology: Insights from natural language processing (NLP)-driven co-occurrence analysis | Immuno-oncology, a rapidly evolving field at the forefront of cancer research, leverages the body’s immune system to fight cancer. In this follow up report, we extend our natural language processing (NLP)-based analysis to pinpoint the context of emergence of the previously identified emerging concepts. To achieve this relational analysis, we devised a method to identify terms co-occurring in a single sentence in the title or abstract of >350,000 journal and patent publications. The focus of the current study was on inter-group co-occurrences, namely between therapeutic targets, biomarkers, types of therapy, and types of cancer. Our analysis indicates that co-occurring concept pairs tend to be scattered between two extremes – potentially emerging concept pairs with rapid growth in publications over the last few years but an overall small number of publications and more well-established concept pairs with modest growth in publications but an overall larger volume of publications. | Kavita A Iyer; Rumiana Tenchov; Julian M Ivanov; Qiongqiong Angela Zhou | Biological and Medicinal Chemistry; Biochemistry; Cell and Molecular Biology; Drug Discovery and Drug Delivery Systems | CC BY 4.0 | CHEMRXIV | 2025-01-08 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/677c0488fa469535b9fa119d/original/emerging-concepts-in-immuno-oncology-insights-from-natural-language-processing-nlp-driven-co-occurrence-analysis.pdf |
65b8bbf19138d23161075bb9 | 10.26434/chemrxiv-2024-h23vm | Chasing new targets to fight antimicrobial resistance: identification of small molecules affecting the interaction of human hemoglobin with the IsdB hemophore of Staphylococcus aureus | Human hemoglobin (Hb) is the preferred iron source of Staphylococcus aureus. This pathogenic bacterium exploits a sophisticated protein machinery called Iron-regulated surface determinant (Isd) system to bind Hb, extract and internalize heme and finally degrade it to complete iron acquisition. IsdB, the surface exposed Hb receptor, is a proven virulence factor of S. aureus and the inhibition of its interaction with Hb can be pursued as a strategy to develop new classes of antimicrobials. To identify small molecules able to disrupt IsdB:Hb protein-protein interactions (PPIs), we carried out a structure-based virtual screening campaign and developed an ad-hoc immunoassay to screen the retrieved set of commercially available compounds. Saturation-transfer difference (STD) NMR was applied to verify specific interactions of a sub-set of molecules, chosen based on their efficacy in reducing the amount of Hb bound to IsdB. Among molecules for which direct binding was verified, the best hit was submitted to ITC analysis to measure the binding affinity to Hb, which was found to be in the sub-micromolar range. The results demonstrate the viability of the proposed in silico/in vitro experimental pipeline to discover and test IsdB:Hb PPI inhibitors. The identified lead compound will be the starting point for future SAR and molecule optimization campaigns. | Monica Cozzi; Maria Cristina Failla; Eleonora Gianquinto; Sandra Kovachka; Valeria Buoli Comani; Carlotta Compari; Omar De Bei; Roberta Giaccari; Francesco Marchesani; Marialaura Marchetti; Luca Ronda; Barbara Rolando; Massimo Baroni; Gabriele Cruciani; Barbara Campanini; Stefano Bettati; Serena Faggiano; Loretta Lazzarato; Francesca Spyrakis | Biological and Medicinal Chemistry; Biochemistry; Drug Discovery and Drug Delivery Systems | CC BY NC ND 4.0 | CHEMRXIV | 2024-01-31 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/65b8bbf19138d23161075bb9/original/chasing-new-targets-to-fight-antimicrobial-resistance-identification-of-small-molecules-affecting-the-interaction-of-human-hemoglobin-with-the-isd-b-hemophore-of-staphylococcus-aureus.pdf |
6541215ea8b423585aa75410 | 10.26434/chemrxiv-2023-rwvkk | Screening and discovery of metal compound active sites for strong and selective adsorption of N2 in air | Photocatalytic nitrogen fixation has the potential to provide a greener route for producing nitrogen-based fertilizers under ambient conditions. Computational screening is a promising route to discover new materials for the nitrogen fixation process, but requires identifying "descriptors" that can be efficiently computed. In this work, we argue that selectivity toward the adsorption of molecular nitrogen and oxygen can act as a key descriptor. A catalyst that can selectively adsorb nitrogen and resist poisoning of oxygen and other molecules present in air has the potential to facilitate the nitrogen fixation process under ambient conditions. We provide a framework for active site screening based on multifidelity density functional theory (DFT) calculations for a range of metal oxides, oxyborides, and oxyphosphides. The screening methodology consists of initial low-fidelity fixed geometry calculations and a second screening in which more expensive geometry optimizations were performed. The approach identifies promising active sites on several TiO2 polymorph surfaces and a VBO4 surface, and the full nitrogen reduction pathway is studied with the BEEF-vdW and HSE06 functionals on two active sites. The findings suggest that meta-stable TiO2 polymorphs may play a role in photocatalytic nitrogen fixation, and that VBO4 may be an interesting material for further studies. | Nianhan Tian; Benjamin Comer; Andrew Medford | Theoretical and Computational Chemistry; Catalysis; Computational Chemistry and Modeling; Heterogeneous Catalysis; Photocatalysis | CC BY NC ND 4.0 | CHEMRXIV | 2023-11-01 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/6541215ea8b423585aa75410/original/screening-and-discovery-of-metal-compound-active-sites-for-strong-and-selective-adsorption-of-n2-in-air.pdf |
65cf299466c1381729c7086b | 10.26434/chemrxiv-2023-93gm5-v2 | Comprehensive Mass Spectrometric Metabolomic Profiling of a Chemically Diverse Collection of Plants of the Celastraceae Family | Natural products exhibit interesting structural features and significant biological activities. The discovery of new bioactive molecules is a complex process that requires high-quality metabolite profiling data to properly target the isolation of compounds of interest and enable their complete structural characterization. The same metabolite profiling data can also be used to understand chemotaxonomic links between species better. This Data Descriptor details a dataset resulting from the untargeted liquid chromatography-mass spectrometry profiling of 76 natural extracts of the Celastraceae family. The spectral annotation results and related chemical and taxonomic metadata are shared, along with proposed examples of data reuse. This data can be further studied by researchers exploring the chemical diversity of natural products. This can serve as a reference sample set for deep metabolome investigation of this chemically rich plant family. | Luis Quiros; Pierre-Marie Allard; Louis-Felix Nothias; Bruno David; Antonio Grondin; Jean-Luc Wolfender | Organic Chemistry; Analytical Chemistry; Chemoinformatics; Mass Spectrometry | CC BY 4.0 | CHEMRXIV | 2024-02-16 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/65cf299466c1381729c7086b/original/comprehensive-mass-spectrometric-metabolomic-profiling-of-a-chemically-diverse-collection-of-plants-of-the-celastraceae-family.pdf |
62b961a67da6ce1160220520 | 10.26434/chemrxiv-2022-20ts5 | Covalently Functionalized Egyptian Blue Nanosheets for Near-Infrared Bioimaging | Fluorophores emitting in the near-infrared (NIR) wavelength region present optimal characteristics for photonics and especially bioimaging. Unfortunately, only few NIR fluorescent materials are known and even fewer are biocompatible. For this reason, the scientific interest in designing novel NIR fluorophores is very high. Egyptian Blue (CaCuSi4O10, EB) is a NIR fluorescent layered silicate that can be exfoliated into fluorescent nanosheets (EB-NS). So far, its surface chemistry has not been tailored but this is crucial for colloidal stability and biological targeting. Here, we demonstrate covalent surface functionalization of EB nanosheets (EBfunc) via Si-H activation using hydrosilanes with variable functionalities. EB-NS were first grafted with the visible fluorescent pyrene (Pyr) moieties to prove conjugation by colocalization of the Vis/NIR fluorescence on the (single) EB-NS level. The same procedure was performed and validated with carboxyl group (COOH)-containing hydrosilanes. These groups can serve as generic handle for further (bio)functionalization of the EB-NS surface. Finally, folic acid (FA) was conjugated to these COOH-functionalized EB-NS to target folic acid receptor-expressing cancer cells. These results highlight the potential of this surface chemistry approach to modify EB-NS and enable targeted NIR imaging for biomedical applications. | Gabriele Selvaggio; Niklas Herrmann; Björn Hill; Riza Dervisoglu; Sebastian Jung; Milan Weitzel; Meshkat Dinarvand; Dietmar Stalke; Loren Andreas; Sebastian Kruss | Physical Chemistry; Biological and Medicinal Chemistry; Nanoscience; Bioengineering and Biotechnology; Optics; Surface | CC BY NC 4.0 | CHEMRXIV | 2022-06-28 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/62b961a67da6ce1160220520/original/covalently-functionalized-egyptian-blue-nanosheets-for-near-infrared-bioimaging.pdf |
666c330d5101a2ffa894bf11 | 10.26434/chemrxiv-2024-qp5bb | Germanium Distributions in Zeolites Derived from Neural Network Potentials. | Germanosilicate zeolites have played a pivotal role in the recent surge in synthesis of novel zeolite topologies. This success has been attributed to the combined effect of the high hydrolytic lability and specific distribution of germanium within the zeolitic framework, e.g., favoring the double four-ring (D4R) structural units. While experimental determination of germanium distributions remains limited, their in silico investigation has been hampered by the high computational cost of ab initio calculations. To overcome these limitations, we have developed neural network potentials (NNPs) that can efficiently explore a wide range of distributions in germanosilicate zeolites, while maintaining the accuracy of the ab initio (dispersion-corrected GGA DFT) training dataset. Through comprehensive screening of low-energy germanium distributions for five zeolite topologies (UTL, BEC, UOV, IWW and *CTH) across a broad range of Si/Ge ratios, we have identified a key factor governing the distribution of germanium in these D4R-containing zeolites, which is the tendency of germanium to cluster. The clustering initiates at the D4R units, leading to a preference to occupy these units at low to medium Ge loading (Si/Ge > 5). However, at high Ge loading, the Ge tends to phase separate into Ge-rich and Ge-poor regions, regardless of the specific structural unit. The zeolite topology was shown to be capable of modulating these trends in germanium distribution (e.g., UTL strongly favors D4R occupation even for low Si/Ge ratios), which suggests the possibility to develop design strategies for targeted zeolite synthesis. The NNPs presented herein enable rapid evaluation of these design strategies across a wide range of candidate zeolite structures and experimentally relevant Si/Ge ratios. | Indranil Saha; Andreas Erlebach; Petr Nachtigall; Christopher J. Heard; Lukáš Grajciar | Theoretical and Computational Chemistry; Materials Science; Catalysts; Nanostructured Materials - Materials; Machine Learning | CC BY 4.0 | CHEMRXIV | 2024-06-19 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/666c330d5101a2ffa894bf11/original/germanium-distributions-in-zeolites-derived-from-neural-network-potentials.pdf |
60c7550af96a004a8d288796 | 10.26434/chemrxiv.14029313.v1 | Air-Stable and Visible-Light-Active P-Type Organic Long-Persistent-Luminescence System by Using Organic Photoredox Catalyst | <p>Organic long-persistent-luminescent (OLPL) materials that exhibit hour-long
photoluminescence have advantages over inorganic materials, such as a sustainability,
flexibility, and processability. The OLPL materials store the absorbed energy
in an intermediate charge-separated state, but this charge-separated state is
unstable to oxygen and does not exhibit persistent luminescence in air. The
excitation wavelength of OLPL can be controlled by electron-donor and -acceptor
materials, but previous materials require absorption mainly in the ultraviolet region.</p><p>
Here, we show OLPL systems that exhibit a persistent luminescence in air
and can be excited by a wavelength from 300-nm to 600-nm. By using cationic
photoredox catalysts as an electron-accepting dopant, stable charge-separated
states are generated by the hole-diffusion
process, as opposed to previous OLPL systems that depend on electron diffusion.
By using a hole-diffusion mechanism and reducing the energy level of the lowest
unoccupied molecular orbital, the OLPL system becomes stable in air and can be
excited by visible light. The addition of hole-trapping material increases the
LPL duration..</p> | Kazuya Jinnai; Ryota Kabe; Zesen Lin; Chihaya Adachi | Photochemistry (Org.); Optical Materials; Photochemistry (Physical Chem.) | CC BY NC ND 4.0 | CHEMRXIV | 2021-02-16 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/60c7550af96a004a8d288796/original/air-stable-and-visible-light-active-p-type-organic-long-persistent-luminescence-system-by-using-organic-photoredox-catalyst.pdf |
62bea1887b3b30165c096b40 | 10.26434/chemrxiv-2022-7z27b | Human-in-the-loop assisted de novo molecular design | A de novo molecular design workflow can be used together with technologies such as reinforcement learning to navigate the chemical space. A bottleneck in the workflow that remains to be solved is how to integrate human feedback in the exploration of the chemical space to optimize molecules. A human drug designer still needs to design the goal, expressed as a scoring function for the molecules that captures the designer’s implicit knowledge about the optimization task. Little support for this task exists and, consequently, a chemist usually resorts to iteratively building the objective function of multi-parameter optimization (MPO) in de novo design. We propose a principled approach to use human-in-the-loop machine learning to help the chemist to adapt the MPO scoring function to better match their goal. An advantage is that the method can learn the scoring function directly from the user’s feedback while they browse the output of the molecule generator, instead of the current manual tuning of the scoring function with trial and error. The proposed method uses a probabilistic model that captures the user’s idea and uncertainty about the scoring function, and it uses active learning to interact with the user. We present two case studies for this: In the first use-case, the parameters of an MPO are learned, and in the second use-case a non-parametric component of the scoring function to capture human domain knowledge is developed. The results show the effectiveness of the methods in two simulated example cases with an oracle, achieving significant improvement in less than 200 feedback queries, for the goals of a high QED score and identifying potent molecules for the DRD2 receptor, respectively. We further demonstrate the performance gains with a medicinal chemist interacting with the system. | Iiris Sundin; Alexey Voronov; Haoping Xiao; Kostas Papadopoulos; Esben Jannik Bjerrum; Markus Heinonen; Atanas Patronov; Samuel Kaski; Ola Engkvist | Theoretical and Computational Chemistry; Computational Chemistry and Modeling; Machine Learning; Artificial Intelligence | CC BY 4.0 | CHEMRXIV | 2022-07-04 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/62bea1887b3b30165c096b40/original/human-in-the-loop-assisted-de-novo-molecular-design.pdf |
648bf29b4f8b1884b75f77b6 | 10.26434/chemrxiv-2023-fv8dp | Bridging the Gap Between Primitive and Modern Phase Separation | Liquid-liquid phase separation (LLPS) is a process that often occurs due to binding between oppositely charged biopolymers, and has gained increasing attention recently due to their ubiquity in biological systems and ability to direct essential cellular processes. For example, aberrant biological LLPS can lead to the emergence and progression of various diseases and disorders, and many significant advances have been made in the biological phase separation field. However, while these discoveries in biology are recent, the field of origins of life has been investigating LLPS for nearly 100 years, ever since the first suggestions by Oparin and Haldane that primitive LLPS could have been precursors to the first cells on Earth. Since then, a significant amount of work has been done to elucidate different primitive LLPS systems that could have been relevant as protocellular models. Given the structural similarities between primitive LLPS and modern membraneless organelles, there may even be an evolutionary link between the two, although this remains a question to be answered. Nevertheless, in order to answer this, a source that compares aspects of modern and primitive LLPS is necessary. Here, we first focus on the assembly of membraneless organelles from intrinsically disordered proteins (IDPs) and nucleic acids, and discuss an example by which aberrant LLPS can result in progression of a disease (tumorigenesis). Then, as a parallel, we explore assembly of primitive membraneless compartments from simple biopolymers such as short peptides and nucleic acids. This is followed by a discussion of how the first biomolecules on Earth may have originated, analyzing the environmental and chemical conditions that could have favored primitive LLPS processes. Finally, we directly compare various aspects of LLPS assembly from both a primitive and a modern perspective, further discussing the potential of primitive IDPs on early Earth, but also the evolution from membraneless to membrane-bound cells. This review aims to provide a comparison of modern and primitive phase separation, including assembly and function, in order to help researchers in both fields understand the current state of knowledge, how this knowledge evolved, and the current gaps that need to be further addressed. | Selene M.C. Cannelli; Ritvik Gupta; Tan Nguyen; Arunava Poddar; Srishti Sharma; Prachiti V. Vithole; Tony Z. Jia | Biological and Medicinal Chemistry; Polymer Science; Earth, Space, and Environmental Chemistry; Biopolymers; Biochemistry; Biophysics | CC BY 4.0 | CHEMRXIV | 2023-06-20 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/648bf29b4f8b1884b75f77b6/original/bridging-the-gap-between-primitive-and-modern-phase-separation.pdf |
638283f428c1646183593f99 | 10.26434/chemrxiv-2022-6nh2p | Dissolution of Soda-Lime Glass in Beverages | The objective of this experiment was to measure and analyze the effect of various beverages on
soda-lime silicate glasses. The beverages included milk, orange juice, and coca-cola. It was
hypothesized that these common beverages would have little effect on the glass particles by
causing minimal degradation. XRD on our samples revealed that our glass was amorphous. The
results of this experiment supported this hypothesis. The pH and weight-loss measurements both
changed very little over the course of the experiment, indicating that the soda-lime silicate
glasses did not dissolve very much in the beverages nor had much of an effect on them. It is
recommended that more beverages be tried with longer time durations to determine the aggregate
effect of acidic liquids on glass bottles and whether or not they are safe for drinking. | Vedant Badoni | Materials Science | CC BY NC 4.0 | CHEMRXIV | 2023-03-23 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/638283f428c1646183593f99/original/dissolution-of-soda-lime-glass-in-beverages.pdf |
60c74c9a0f50db023b396e96 | 10.26434/chemrxiv.12253277.v2 | Elucidating the Weakly Reversible Cs-Pb-Br Perovskite Nanocrystal Reaction Network with High-Throughput Maps and Transformations | <p>Advances
in automation and data analytics can aid exploration of the complex chemistry
of nanoparticles. Lead halide perovskite colloidal nanocrystals provide an
interesting proving ground: there are reports of many different phases and
transformations, which has made it hard to form a coherent conceptual framework
for their controlled formation through traditional methods. In this work, we systematically explore the portion of Cs-Pb-Br
synthesis space in which many optically distinguishable species are formed using high-throughput robotic synthesis to understand their formation reactions. We deploy an automated method
that allows us to determine the relative amount of absorbance that can be
attributed to each species in
order to create maps of the synthetic space. These in turn facilitate improved
understanding of the interplay between kinetic and thermodynamic factors that underlie which
combination of species are likely to be prevalent under a given set of
conditions. Based on these
maps, we test potential transformation routes between perovskite nanocrystals
of different shapes and
phases. We find that shape is determined kinetically, but many reactions between different phases show equilibrium behavior. We
demonstrate a dynamic equilibrium between complexes, monolayers and
nanocrystals of lead bromide, with substantial impact on the reaction outcomes.
This allows us to construct a chemical reaction
network that qualitatively explains our results as
well as previous reports and can serve as a guide for those seeking to prepare
a particular composition and shape. </p> | Jakob Dahl; Xingzhi Wang; Xiao Huang; Emory Chan; Paul Alivisatos | Nanostructured Materials - Nanoscience; Kinetics and Mechanism - Inorganic Reactions; Physical and Chemical Processes; Robotics | CC BY NC ND 4.0 | CHEMRXIV | 2020-06-12 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/60c74c9a0f50db023b396e96/original/elucidating-the-weakly-reversible-cs-pb-br-perovskite-nanocrystal-reaction-network-with-high-throughput-maps-and-transformations.pdf |
67c39135fa469535b985ff55 | 10.26434/chemrxiv-2025-tm4ff-v2 | An Efficient Workflow for Generation of Conformational Ensembles of Density Functional Theory Quality: Dimers of Polycyclic (Hetero-)Aromatics | Several composite density functional theory (DFT) methods, namely HF-3c, B97- 3c, PBEh-3c, r2SCAN-3c, and ωB97X-3c, were tested for accuracy and efficiency in computing binding energies of seven low-lying conformers of the pyrene homodimer, both in the gas phase and in toluene solution. The most promising method was B97-3c, with a Mean Absolute Deviation (MAD) for binding energies of 0.5 kJ/mol, relative to ωB97X-V/def2-TZVP results. Thus, B97-3c was used in a multi-tiered approach for generating conformational ensembles for a series of homodimers. The workflow involves six steps: (i) generate an initial ensemble, using the conformer-rotamer ensemble sam- pling tool (CREST), and its underlying GFN2-xTB method; (ii) reoptimize each mem- ber of the ensemble using B97-3c; (iii) discard duplicates and high-energy conformers; (iv) reoptimize the remaining conformers using ωB97X-D4/def2-SVP; (v) if needed, discard any high energy or duplicate conformers; (vi) compute vibrational frequencies using ωB97X-D4/def2-SVP and final single point energies using ωB97X-V/def2- QZVPP. The six-step workflow allows the generation of large DFT-quality ensembles efficiently, as demonstrated on the known pyrene dimer ensemble, and then applied to the homodimers of eight small polycyclic (hetero-)aromatic molecules related to asphaltenes: anthracene, phenanthrene, fluorenone, dibenzofuran, dibenzothiophene, dibenzothiophene oxide, N -methylcarbazole, and benzo[h]quinoline. The refined ensembles enabled an analysis of trends in dimerization structures and energies for these monomers, revealing a strong dependence for binding energy upon the magnitude of dipole cancellation. | Jessica J Ortlieb; Nathanael J King; Alex Brown | Theoretical and Computational Chemistry; Computational Chemistry and Modeling | CC BY 4.0 | CHEMRXIV | 2025-03-04 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/67c39135fa469535b985ff55/original/an-efficient-workflow-for-generation-of-conformational-ensembles-of-density-functional-theory-quality-dimers-of-polycyclic-hetero-aromatics.pdf |
65b9241ce9ebbb4db94c8b14 | 10.26434/chemrxiv-2024-s5sbs | Binding Affinity Prediction with 3D Machine Learning: Training Data and Challenging External Testing | Protein-ligand binding affinity prediction is one of the major challenges in computational assisted drug discovery. An active area of research uses machine learning (ML) models trained on 3D structures of protein ligand complexes to predict binding modes, discriminate active and inactives, or predict affinity. Methodological advances in deep learning, and artificial intelligence along with increased experimental data (3D structures and bioactivities) has led to many studies using different architectures, representation, and features. Unfortunately, many models do not learn details of interactions or the underlying physics that drive protein-ligand affinity, but instead just memorize patterns in the available training data with poor generalizability and future use. In this work we incorporate “dense”, feature rich datasets that contain up to several thousand analogue molecules per drug discovery target. For the training set, PDBbind dataset is used with enrichment from 8 internal lead optimization (LO) datasets and inactive and decoy poses in a variety of combinations. A variety of different model architectures was used and the model performance was validated using the binding affinity for 12 internal LO and 6 ChEMBL external test sets. Results show a significant improvement in the performance and generalization power, especially for virtual screening and suggest promise for the future of ML protein-ligand affinity prediction with a greater emphasis on training using datasets that capture the rich details of the affinity landscape. | Jose Carlos Gómez-Tamayo; Lili Cao; Mazen Ahmad; Gary Tresadern | 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 | 2024-02-01 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/65b9241ce9ebbb4db94c8b14/original/binding-affinity-prediction-with-3d-machine-learning-training-data-and-challenging-external-testing.pdf |
65aea5a166c1381729074278 | 10.26434/chemrxiv-2024-lh431 | AF4-MALS-SP ICP-ToF-MS analysis gives insight into nature of HgSe nanoparticles formed by cetaceans. | Cetaceans are known to accumulate very high levels of mercury (Hg) and unlike fish species, most of the mercury is not present as methylmercury (MeHg) but instead as inorganic Hg. It has been suggested this is a result of a detoxification process which involves the sequestering of Hg by Se-containing proteins, concluding with the formation of HgSe nanoparticles. However, their elemental compositions besides Hg and Se, as well as their genesis are unknown. We applied asymmetric flow-field flow fractionation - multiangle laser light scattering (AF4 -MALS) coupled to single particle inductively coupled plasma - time of flight - mass spectrometry (SP ICP-ToF-MS) for the size-dependant separation, counting and further elemental characterisation of of Hg/Se-containing nanoparticles in the liver and cerebellum of a sperm whale. Using a proteinase K digestion method, we isolated and identified particles which had size-independent masses of Hg and as well as a continuous molar ratio of Hg to Se. We also identified Cd and Sn on particles alongside Hg and Se, which indicated the detoxification process resulting in Hg/Se nanoparticles may not be specific to MeHg. This data indicates nanoclusters of toxic elements, bound to selenium, make up a nanoparticle core which is surrounded by a larger non-metal(loid) corona. | Lhiam Paton; Thebny Thaíse Moro; Thomas Lockwood; Tatiane de Andrade Maranhão; Gerhard Goessler; David Clases; Joerg Feldmann | Analytical Chemistry; Nanoscience; Earth, Space, and Environmental Chemistry | CC BY NC 4.0 | CHEMRXIV | 2024-01-24 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/65aea5a166c1381729074278/original/af4-mals-sp-icp-to-f-ms-analysis-gives-insight-into-nature-of-hg-se-nanoparticles-formed-by-cetaceans.pdf |
613fbd9aabeb630e3fd1aa8e | 10.26434/chemrxiv-2021-5twk7-v3 | Design, Synthesis and Biological Evaluation of Novel SARS-CoV-2 3CLpro Covalent Inhibitors | Severe diseases such as the ongoing COVID-19 pandemic, as well as the previous SARS and MERS outbreaks, are the result of coronavirus infections and have demonstrated the
urgent need for antiviral drugs to combat these deadly viruses. Due to its essential role in viral replication and function, 3CLpro> has been identified as a promising target for the development of antiviral drugs.
Previously reported SARS-CoV 3CLpro non-covalent inhibitors were used as a starting point for the development of covalent inhibitors of SARS-CoV-2 3CLpro. We report herein our efforts in design and synthesis which led to submicromolar covalent inhibitors when the enzymatic activity of the viral protease was used as a screening platform. | Julia Stille; Jevgenijs Tjutrins; Guanyu Wang; Felipe A. Venegas; Christopher Hennecker; Andres Mauricio Rueda; Itai Sharon; Nicole Blaine; Caitlin E. Miron; Sharon Pinus; Anne Labarre; Jessica Plescia; Mihai Burai Patrascu; Xiaocong Zhang; Alexander S. Wahba; Danielle Vlaho; Mitchell Huot; T. Martin Schmeing; Anthony K Mittermaier; Nicolas Moitessier | Biological and Medicinal Chemistry; Drug Discovery and Drug Delivery Systems | CC BY NC ND 4.0 | CHEMRXIV | 2021-09-14 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/613fbd9aabeb630e3fd1aa8e/original/design-synthesis-and-biological-evaluation-of-novel-sars-co-v-2-3c-lpro-covalent-inhibitors.pdf |
6154ba8d9e384038a344dd7b | 10.26434/chemrxiv-2021-64461 | The catalytic mechanism of the Suzuki-Miyaura reaction | Abstract: Experimental and theoretical 13C kinetic isotope effects are utilized to obtain atomistic insight into the catalytic mechanism of the Pd(PPh3)4 catalyzed Suzuki-Miyaura reaction of aryl halides and aryl boronic acids. Under catalytic conditions, we establish that oxidative addition of aryl bromides occurs to a 12-electron monoligated palladium complex (Pd(PPh3)). For aryl iodides, the first irreversible step in the catalytic cycle precedes oxidative addition and is shown to be binding of the iodoarene to Pd(PPh3). Our results suggest that the commonly proposed oxidative addition to the 14-electron Pd(PPh3)2 complex can occur only in the presence of excess added ligand or under stoichiometric conditions. The transmetalation step, under catalytic conditions, is shown to proceed via a tetracoordinate boronate (8B4) intermediate with a Pd-O-B linkage. | Juliet macharia; Chetan Joshi; Joseph Izzo; Victor Wambua; Sungjin Kim; Jennifer Hirschi; Mathew Vetticatt | Organic Chemistry; Catalysis; Organometallic Chemistry; Physical Organic Chemistry; Catalysis; Kinetics and Mechanism - Organometallic Reactions | CC BY NC 4.0 | CHEMRXIV | 2021-09-30 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/6154ba8d9e384038a344dd7b/original/the-catalytic-mechanism-of-the-suzuki-miyaura-reaction.pdf |
641e2c32647e3dca99750edf | 10.26434/chemrxiv-2023-5ht3d | High-throughput identification of crystalline natural products from crude extracts enabled by microarray technology and microED | The structural determination of natural products (NPs) can be arduous due to sample heterogeneity. This often demands itera-tive purification processes and characterization of complex molecules that may only be available in miniscule quantities. Microcrystal electron diffraction (microED) has recently shown promise as a method to solve crystal structures of NPs from nanogram quantities of analyte. However, its implementation in NP discovery remains hampered by sample throughput and purity requirements akin to traditional NP-discovery workflows. In the methods described herein, we leverage the resolving power of transmission electron microscopy (TEM) and the miniaturization capabilities of DNA microarray technology to address these challenges through the establishment of an NP screening platform, array electron diffraction (ArrayED). In this workflow, an array of HPLC fractions taken from crude extracts are deposited onto TEM grids in picoliter-sized droplets. This multiplexing of analytes on TEM grids enables 1200 or more unique samples to be simultaneously inserted into a TEM equipped with an autoloader. Selected area electron diffraction analysis of these microarrayed grids allows for rapid identification of crystalline metabolites. In this study, ArrayED enabled structural characterization of 14 natural products, including four novel crystal structures and two novel polymorphs, from 20 crude extracts. Moreover, we identify several chemical species that would not be detected by standard mass spectrometry (MS) or UV/Vis and crystal forms that would not be characterized using traditional methods. | David Delgadillo; Jessica Burch; Lee Joon Kim; Lygia de Moraes; Kanji Niwa; Jason Williams; Melody Tang; Vincent Lavallo; Bhuwan Chhetri; Christopher Jones; Isabel Hernandez Rodriguez; Joshua Signore; Lewis Marquez; Riya Bhanushali; Madison Greene; Sunmin Woo; Julia Kubanek; Cassandra Quave; Yi Tang; Hosea Nelson | Organic Chemistry; Natural Products; Organic Compounds and Functional Groups; Crystallography – Organic | CC BY NC ND 4.0 | CHEMRXIV | 2023-03-27 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/641e2c32647e3dca99750edf/original/high-throughput-identification-of-crystalline-natural-products-from-crude-extracts-enabled-by-microarray-technology-and-micro-ed.pdf |
60d9e4fcc622959f751b784e | 10.26434/chemrxiv-2021-sp390 | Local Electric Fields Dictate Function: The Different Product Selectivity Observed for Fatty Acids Oxidation by Two Deceptively Very Similar P450-Peroxygenases OleT and BSbeta | Cytochrome P450 peroxygenases use hydrogen peroxide to hydroxylate long-chain fatty acids by bypassing the use of O 2 and a redox partner. Among the peroxygenases, P450 OleT uniquely performs decarboxylation of fatty acids and production of terminal olefins. This root taken by P450 OleT is intriguing, and its importance is augmented by the practical importance of olefin production. As such, this mechanistic choice merits elucidation. To address this puzzle we use hybrid QM/MM calculations and MD simulations for the OleT enzyme as well as for the structurally analogous enzyme, P450 BSβ . The study of P450 OleT reveals that the protonated His85 in the wild-type P450 OleT , plays a crucial role in steering decarboxylation activity by stabilizing the corresponding hydroxoiron(IV) intermediate (Cpd II). In contrast, for P450 BSβ in which Q85 replaces H85, the respective Cpd II species is unstable and it reacts readily with the substrate radical by rebound, producing hydroxylation products. As we show, this single-site difference creates in P450 OleT a local electric field (LEF), which is significantly higher than that in P450 BSβ . In turn, these LEF differences are responsible for the different stabilities of the respective Cpd II/radical intermediates, and hence for different functions of the two enzymes. P450 BSβ uses the common rebound mechanism and leads to hydroxylation, whereas P450 OleT proceeds via decarboxylation and generates terminal olefins. Olefin production projects the power of a single residue to alter the LEF and the enzyme’s function! | Shalini Yadav; Sason Shaik; Shakir Ali Siddiqui; Surajit Kalita; Kshatresh Dubey | Theoretical and Computational Chemistry; Catalysis; Organometallic Chemistry; Computational Chemistry and Modeling; Biocatalysis; Kinetics and Mechanism - Organometallic Reactions | CC BY 4.0 | CHEMRXIV | 2021-06-29 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/60d9e4fcc622959f751b784e/original/local-electric-fields-dictate-function-the-different-product-selectivity-observed-for-fatty-acids-oxidation-by-two-deceptively-very-similar-p450-peroxygenases-ole-t-and-b-sbeta.pdf |
618a66fa7a002183bd4c320f | 10.26434/chemrxiv-2021-m73h6 | Tuning the Photocatalytic Activity of Layered Perovskite Niobates by Controlled Ion Exchange and Hydration | Dion-Jacobson type layered perovskite niobium oxides KCa2Nb3O10 and KSr2Nb3O10 were prepared via molten salt method, and the potassium cations were exchanged by protons using nitric acid. Different degrees of proton exchange were adjusted, and the dependence of photocatalytic activity for hydrogen evolution on proton exchange was investigated. Moreover, proton exchange leads to different amounts of water incorporated into the interlayer spaces, also influencing photocatalytic performance significantly. Decoupling water intercalation and proton exchange, the photocatalytic activity of proton exchanged KCa2Nb3O10 and KSr2Nb3O10 can be revealed and tailored for maximum activity. | Calin Ladasiu; Natalia Kulischow; Roland Marschall | Materials Science; Catalysis; Energy; Photocatalysis | CC BY NC ND 4.0 | CHEMRXIV | 2021-11-10 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/618a66fa7a002183bd4c320f/original/tuning-the-photocatalytic-activity-of-layered-perovskite-niobates-by-controlled-ion-exchange-and-hydration.pdf |
663c999191aefa6ce18f812d | 10.26434/chemrxiv-2024-v5g2s | Iridium-Catalyzed Enantioselective Vinylogous and Bisvinylogous Allenylic Substitution | Compared to the widely explored enol silanes, applicability of their extended variants especially as bisvinylogous nucleophile in enantioselective catalysis has been sparse. Herein, we describe the first enantioselective vinylogous and bisvinylogous allenylic substitution using silyl dienol and trienol ethers, respectively, as nucleophile. With racemic allenylic alcohols as electrophile, these enantioconvergent reactions are cooperatively catalyzed by an Ir(I)/(phosphoramidite,olefin) complex and Lewis acidic La(OTf)3, and display remarkable regio- and diastereoselectivity in most cases. The ability of such extended silyl enol ethers in distant functionalization and creation of remote stereocenters is evident from the resulting γ- and ε-allenylic unsaturated ketones, bearing δ- and ζ-stereocenters respectively, which are obtained in moderate to high yield with good to excellent enantioselectivity. The synthetic utility of these unsaturated carbonyls bearing an allene moiety is demonstrated with several transformations, including controlled reductions and stereoselective olefinations which lead to products with desired degrees of unsaturation. | Sankash Mitra; Santanu Mukherjee | Organic Chemistry; Catalysis; Organic Synthesis and Reactions; Stereochemistry; Homogeneous Catalysis | CC BY NC ND 4.0 | CHEMRXIV | 2024-05-10 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/663c999191aefa6ce18f812d/original/iridium-catalyzed-enantioselective-vinylogous-and-bisvinylogous-allenylic-substitution.pdf |
668b4fabc9c6a5c07a9e4906 | 10.26434/chemrxiv-2024-920x2 | Trifluoroacetic Acid Mediated Additive-free Late-Stage Native Pep-tide Cyclization to Form Disulfide Mimetics via Thioketalization with Ketones | Peptide cyclization is often used to introduce conformational rigidity and enhance the physiological stability of the peptide. This study presents a novel late-stage cyclization method for creating thioketal cyclic peptides from bis-cysteine peptides and drugs. Symmetrical cyclic ketones and acetone were found to react with bis-cysteine unprotected peptides efficiently to form thioketal linkages in trifluoroacetic acid (TFA) without any other additive. The attractive features of this method include high chemoselec-tivity, operational simplicity, robustness. In addition, TFA as the reaction solvent can dissolve any unprotected peptide. As a showcase, the dimethyl thioketal versions of lanreotide and octreotide were prepared and evaluated, both of which showed much improved reductive stability and comparable activity. | Yisa XIAO; Haiyan ZHOU; Han Liu; Xuechen Li | Organic Chemistry | CC BY NC ND 4.0 | CHEMRXIV | 2024-07-09 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/668b4fabc9c6a5c07a9e4906/original/trifluoroacetic-acid-mediated-additive-free-late-stage-native-pep-tide-cyclization-to-form-disulfide-mimetics-via-thioketalization-with-ketones.pdf |
62583cfbbdc9c26845d47c58 | 10.26434/chemrxiv-2022-4wm4t | Site-Selective, Stereocontrolled Glycosylation Catalyzed by Bis-Thioureas | The identification of general and efficient methods for the construction of oligosaccharides stands as one of the great challenges for the field of synthetic chemistry. Selective glycosylation of unprotected sugars and other polyhydroxylated nucleophiles is a particularly significant goal, requiring not only control over the stereochemistry of the forming bond but also differentiation between similarly reactive nucleophilic sites in stereochemically complex contexts. Chemists have generally relied on multi-step protecting-group strategies to achieve site control in glycosylations, but practical inefficiencies arise directly from the application of such approaches. We describe here a new strategy for small-molecule-catalyst-controlled, highly stereo- and site-selective glycosylations of unprotected or minimally protected mono- and disaccharides using precisely designed bis-thiourea small-molecule catalysts. Stereo- and site-selective galactosylations and mannosylations of a wide assortment of polyfunctional nucleophiles is thereby achieved. Kinetic and computational studies provide evidence that site selectivity arises from stabilizing C–H/π interactions between the catalyst and the nucleophile, analogous to those documented in sugar-binding proteins. This work demonstrates that highly selective glycosylation reactions can be achieved through control of stabilizing noncovalent interactions, a potentially general strategy for selective functionalization of carbohydrates. | Qiuhan Li; Samuel M. Levi; Corin C. Wagen; Alison E. Wendlandt; Eric N. Jacobsen | Organic Chemistry; Catalysis; Organic Synthesis and Reactions; Organocatalysis | CC BY NC ND 4.0 | CHEMRXIV | 2022-04-15 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/62583cfbbdc9c26845d47c58/original/site-selective-stereocontrolled-glycosylation-catalyzed-by-bis-thioureas.pdf |
6657138321291e5d1d89ef7d | 10.26434/chemrxiv-2024-571sr | Uncovering pH-dependency and interfacial electron-transfer mechanisms of oxygen reduction reaction sites in nitrogen-doped carbon materials | Nitrogen-doped carbon materials (NCMs) are an important class of energy catalytic materials, which are also widely recognized for their excellent electrocatalytic performance, particularly in O2 reduction reaction (ORR). However, many NCMs face the pH-dependency problem in the ORR in that their electrocatalytic performance often changes drastically as the pH of the reaction environment is varied. The underlying interfacial reaction mechanisms and the pH-dependent activity origins for NCMs need to be clarified to put an on end to the long-standing controversy over these issues. In this study, we successfully prepared a set of NCM model catalysts to determine the active sites through a series of careful control experiments. By applying the spectroelectrochemistry-aided catalyst layer voltammetry study method in combination with density functional theory (DFT) calculations, we deeply revealed the roles of different active sites and their interfacial electron-transfer mechanisms in NCMs. Experimental results clearly show that both pyridinic-N and graphitic-N sites exhibited no significant ORR activity under strong acidic conditions. The 1,3-cyclopentadiene-like defects (i.e., edge pentagonal defects) were considered as the main pH-universal active site, due to their unique electronic structure and electrostatic effects, enabling effective adsorption and activation of O2 molecules under acidic, alkaline, and neutral conditions, particularly with the ability to directly dissociate O2 in acidic media. Finally, a pH-performance diagram for the various active sites in NCMs across a broad pH range was presented to understand the chemistry of pH-dependent ORR active sites in NCMs. | Peiyao Bai; Lang Xu | Catalysis; Energy; Electrocatalysis; Heterogeneous Catalysis; Fuel Cells; Materials Chemistry | CC BY NC ND 4.0 | CHEMRXIV | 2024-06-03 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/6657138321291e5d1d89ef7d/original/uncovering-p-h-dependency-and-interfacial-electron-transfer-mechanisms-of-oxygen-reduction-reaction-sites-in-nitrogen-doped-carbon-materials.pdf |
65681b9d29a13c4d4750d1f7 | 10.26434/chemrxiv-2023-1h2w8 | A Multitasking Photoredox-Catalysis for Stereoselective C‒N Bond Formation | A rare photoredox-mediated C‒N bond formation methodology has been developed integrating the concepts of [2+2]-photocycloaddition of styrene in combination with N-centered radical (NCR) generation. Highly significant enamines and imines have been produced in a stereoselective manner using a mild and bench-stable oxime-ester precursor as the N-linchpin. The key attraction is the multitasking catalysis of fac-Ir(ppy)3 involving energy transfer, N-O bond cleavage, N-centered radical generation, imine reduction and cyclobutane ring opening simultaneously in the same reaction pot. Preliminary mechanistic investigations have been performed to have an idea about the mechanism involving both energy transfer mediated cycloaddition and the photoredox mediated iminyl radical generation. Wide functionality tolerance with satisfactory yield and exclusive stereoselectivity are the salient features of this newly discovered methodology. | Biprajit Paul; Surajit Das; Indranil Chatterjee | Organic Chemistry; Catalysis; Organic Synthesis and Reactions; Homogeneous Catalysis; Photocatalysis | CC BY NC ND 4.0 | CHEMRXIV | 2023-12-07 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/65681b9d29a13c4d4750d1f7/original/a-multitasking-photoredox-catalysis-for-stereoselective-c-n-bond-formation.pdf |
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