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60c7562f702a9b08b618c87e | 10.26434/chemrxiv.14204834.v1 | 6,5-Fused Ring, C2-Salvinorin Ester, Dual Kappa and Mu Opioid Receptor Agonists as Analgesics Devoid of Anxiogenic Effects | Analgesia
is commonly mediated through the mu or kappa opioid receptor agonism.
Unfortunately, selective mu or kappa receptor agonists often cause harmful side
effects. Recently, ligands exhibiting dual agonism to the opioid receptors,
such as to mu and kappa, or to mu and delta, have been suggested to temper
undesirable adverse effects while retaining analgesic activity. Herein we report
an introduction of various 6,5-fused rings to C2 of the salvinorin scaffold <i>via</i> an ester linker. <i>In vitro</i> studies
showed that some of these compounds have dual agonism on kappa and mu opioid
receptors, while some have triple agonism on kappa, mu, and delta. <i>In
vivo </i>studies on the lead dual kappa and mu opioid receptor agonist,
compound <b>10</b>, showed that it<b> </b>produced
analgesic activity while avoiding anxiogenic effects in murine models, thus
providing further strong evidence for the therapeutic advantages of dual opioid
receptor agonists over selective opioid receptor agonists. | Nicholas S. Akins; Nisha Mishra; Hannah M. Harris; Narendar Dudhipala; Seong Jong Kim; Adam W. Keasling; Soumyajit Majumdar; Jordan K. Zjawiony; Nicole Ashpole; Hoang V. Le | Drug Discovery and Drug Delivery Systems | CC BY NC ND 4.0 | CHEMRXIV | 2021-03-16 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/60c7562f702a9b08b618c87e/original/6-5-fused-ring-c2-salvinorin-ester-dual-kappa-and-mu-opioid-receptor-agonists-as-analgesics-devoid-of-anxiogenic-effects.pdf |
64f2a6e1dd1a73847ffea193 | 10.26434/chemrxiv-2023-hjnxh | Native Mass Spectrometry Dissects the Structural Dynamics of an Allosteric Heterodimer of SARS-CoV-2 Nonstructural Proteins | Structure-based drug design, which relies on precise understanding of the target protein and its interaction with the drug candidate, is dramatically expedited by advances in computational methods for candidate prediction. Yet, the accuracy needs to be improved with more structural data from high throughput experiments, which are challenging to generate, especially for dynamic and weak associations. Herein, we applied native mass spectrometry (native MS) to rapidly characterize ligand binding of an allosteric heterodimeric complex of SARS-CoV-2 two nonstructural proteins (nsp) nsp10 and nsp16 (nsp10/16). Native MS showed that the dimer is in equilibrium with monomeric states in solution. Consistent with literature, well characterized small co-substrate, RNA substrate and product bind with high specificity and affinity to the dimer but not the free monomers. Unsuccessfully designed ligands bind indiscriminately to all forms. Using neutral gas collision, the nsp16 monomer with bound co-substrate can be released from the holo dimer complex, confirming the binding to nsp16 as revealed by the crystal structure. However, an unusual migration of the endogenous zinc ions bound to nsp10 to nsp16 after collisional dissociation was observed, and can be suppressed using an alternative surface collision method at reduced precursor charge states. This highlighted the importance of careful optimization of experimental techniques. Overall, with minimal sample input (~µg), native MS can rapidly detect ligand binding affinities and locations in dynamic multi-subunit protein complexes, demonstrating the potential of an “all-in-one” native MS assay for rapid structural profiling of protein-to-AI-based compound systems to expedite drug discovery. | Stephanie Thibert; Deseree Reid; Jesse Wilson; Rohith Varikoti; Natalia Maltseva; Katherine Schultz; Agustin Kruel; Gyorgy Babnigg; Andrzej Joachimiak; Neeraj Kumar; Mowei Zhou | Biological and Medicinal Chemistry; Analytical Chemistry; Analytical Chemistry - General; Mass Spectrometry; Drug Discovery and Drug Delivery Systems | CC BY NC ND 4.0 | CHEMRXIV | 2023-09-04 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/64f2a6e1dd1a73847ffea193/original/native-mass-spectrometry-dissects-the-structural-dynamics-of-an-allosteric-heterodimer-of-sars-co-v-2-nonstructural-proteins.pdf |
60c74fcdf96a006583287cf4 | 10.26434/chemrxiv.12948494.v1 | Tricyclic 2-Aminopyridinium Derivatives with Aggregation-Induced Emission for Concomitant Bacterial Discrimination and Inhibition | The development of new ionic compounds with
aggregation-induced emission (AIE) has been widely noticed. They can not only
effectively solve the problem of aggregation-caused quenching (ACQ) encountered
in conventional fluorescent dyes, but also exhibit promising applications in
biological imaging, diagnosis and therapy, etc. However, such AIE system should be further
developed. In this work, <a>a series of</a><a> novel cationic </a>AIE luminogens (AIEgens) of
tricyclic 2-aminopyridinium derivatives <a>with
seven-membered rings</a> were designed and
synthesized <a>via a simple multi-component reaction</a>,
which exhibit the ability to <a>specifically</a> stain
gram-positive bacteria. Meanwhile, they also <a>possess
excellent bacteriostatic ability for <i>S.
aureus</i> in liquid medium and solid agar plates</a>, of which the minimum
inhibitory concentration (MIC) value is between 4 and 8 µg/mL. In addition,
these molecules showed mitochondria-targeting capability in hydrophilic AIEgens
and specific staining lysosomes in lipophilic AIEgens by wash-free process in
living cells. These AIEgens with bacteriostatic activity hold great promise for
distinguishing bacteria and inhibiting bacterial infection in clinical trial. | Bingnan Wang; Haozhong Wu; Rong Hu; Xiaolin Liu; zhiyang liu; Zhiming Wang; Anjun Qin; Ben Zhong Tang | Biological Materials | CC BY NC ND 4.0 | CHEMRXIV | 2020-09-14 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/60c74fcdf96a006583287cf4/original/tricyclic-2-aminopyridinium-derivatives-with-aggregation-induced-emission-for-concomitant-bacterial-discrimination-and-inhibition.pdf |
67175daa12ff75c3a12bd78e | 10.26434/chemrxiv-2024-tkvrh | FEP-SPell-ABFE: An Open-Source Automated
Alchemical Absolute Binding Free Energy
Calculation Workflow for Drug Discovery | The binding affinity between a drug molecule and its target, measured by absolute binding free energy (ABFE), is a crucial factor in the lead discovery phase of drug development. Recent research has highlighted the potential of in silico ABFE predictions to directly aid drug development by allowing for the ranking and prioritization of promising candidates. This paper introduces an open-source Python workflow called FEP-SPell-ABFE, designed to automate ABFE calculations with minimal user involvement. The workflow requires only three key inputs: a receptor protein structure in PDB format, candidate ligands in SDF format, and a configuration file (config.yaml) that governs both workflow and molecular dynamics simulation parameters. It produces a ranked list of ligands along with their binding free energies in Comma-Separated Values (CSV) format. The workflow leverages SLURM (Simple Linux Utility for Resource Management) for automating task execution and resource allocation across modules. A usage example and several benchmark systems for validation are provided. The FEP-SPell-ABFE workflow, along with a practical example, is publicly accessible on GitHub at https://github.com/freeenergylab/FEP-SPell-ABFE, distributed under the MIT License. | Pengfei Li; Tingting Pu; Ye Mei | Theoretical and Computational Chemistry; Computational Chemistry and Modeling | CC BY NC ND 4.0 | CHEMRXIV | 2024-10-23 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/67175daa12ff75c3a12bd78e/original/fep-s-pell-abfe-an-open-source-automated-alchemical-absolute-binding-free-energy-calculation-workflow-for-drug-discovery.pdf |
66a3f36301103d79c5c7f39a | 10.26434/chemrxiv-2024-ksftd | A Photothermocatalytic Reactor and Selective Solar Absorber for Sustainable Fuel Synthesis by Ethylene Oligomerization | Utilizing solar thermal energy for thermochemical processes enables sustainable generation of fuels and chemicals. Here, we present a scalable photothermocatalytic reactor with a selective solar absorber that converts sunlight into thermal energy for fuel synthesis. The fabricated absorber achieves a calculated maximum temperature of 249 °C under one sun illumination and 130 °C under ambient operating conditions (25 °C, 1 atm). The application of the photothermocatalytic reactor was demonstrated using an industrially relevant ethylene oligomerization reaction. A homogeneous reaction was performed in a batch mode and yielded a distribution of liquid hydrocarbon chains with 6 to 24 carbon atoms. A heterogeneous reaction was performed in a flowthrough configuration, yielding butene and hexene products. Finally, simulated results for a larger-scale reactor predict spatially uniform maximum temperatures up to 120 °C and 210 °C under one and three sun illumination, demonstrating the potential to generate fuels at bigger scales. | Magel P. Su; Aisulu Aitbekova; Matthew Salazar; Xueqian Li; Shuoyan Xiong; Matthew Espinosa; Jonas C. Peters; Theodor Agapie; Harry A. Atwater | Materials Science; Catalysis; Energy | CC BY NC ND 4.0 | CHEMRXIV | 2024-07-31 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/66a3f36301103d79c5c7f39a/original/a-photothermocatalytic-reactor-and-selective-solar-absorber-for-sustainable-fuel-synthesis-by-ethylene-oligomerization.pdf |
65804cec66c13817297d108b | 10.26434/chemrxiv-2023-dh131-v2 | Groebke Blackburn Bienaymé-mediated multi-component synthesis of selective HDAC6 inhibitors with anti-inflammatory properties | Histone deacetylases (HDACs) are a class of enzymes that cleave acyl groups from lysine residues of histone and non-histone proteins. There are 18 human HDAC isoforms with different cellular targets and functions. Among them, HDAC6 was found to be overexpressed in different types of cancer. However, when used in monotherapy, HDAC6 inhibition by selective inhibitors fails to show pronounced anti-cancer effects. The HDAC6 enzyme also addresses non-histone proteins like tubulin and cortactin, making it important for cell migration and angiogenesis. Recently, the NLRP3 inflammasome was identified as an important regulator of inflammation and immune responses and, importantly, HDAC6 is critically involved the activation of the inflammasome. We herein report the design, synthesis and biological evaluation of a library of selective HDAC6 inhibitors. Starting from the previously published crystal structure of MAIP-032 in complex with CD2 of zHDAC6, we performed docking studies to evaluate additional possible interactions of the cap group with the L1-loop pocket. Based on the results we synthesized 13 novel HDAC6 inhibitors via the Groebke Blackburn Bienaymé three component reaction as the key step. Compounds 8k (HDAC1 IC50: 5.87 μM; HDAC6 IC50: 0.024 μM; selectivity factor (SF1/6): 245) and 8m (HDAC1 IC50: 3.07 μM; HDAC6 IC50: 0.026 μM; SF1/6: 118) emerged as the most potent and selective inhibitors of HDAC6 and outperformed the lead structure MAIP-032 (HDAC1 IC50: 2.20 μM; HDAC6 IC50: 0.058 μM; SF1/6: 38) both in terms of inhibitory potency and selectivity. Subsequent immunoblot analysis confirmed the high selectivity of 8k and 8m for HDAC6 in a cellular environment. While neither 8k and 8m nor the selectivity HDAC6 inhibitor tubastatin A showed antiproliferative effects in the U 87 MG glioblastoma cell line, compound 8m attenuated cell migration significantly in wound healing assays in U-87 MG cells. Moreover, in macrophages compounds 8k and 8m demonstrated significant inhibition of LPS-induced IL1B mRNA expression and TNF release. These findings suggest that our imidazo[1,2-a]pyridine-capped HDAC6 inhibitors may serve as promising candidates for the development of drugs to effectively treat NLRP3 inflammasome-driven inflammatory diseases. | Fabian Kraft; Jana Enns; Irina Honin; Jonas Engelhardt; Andrea Schöler; Shannon Smith; Jens Meiler; Linda Schäker-Hübner; Günther Weindl; Finn Kristian Hansen | Biological and Medicinal Chemistry | CC BY NC 4.0 | CHEMRXIV | 2023-12-19 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/65804cec66c13817297d108b/original/groebke-blackburn-bienayme-mediated-multi-component-synthesis-of-selective-hdac6-inhibitors-with-anti-inflammatory-properties.pdf |
64bee6e5ae3d1a7b0d46b3a0 | 10.26434/chemrxiv-2023-hbqjd-v2 | Electrochemistry at the edge of a van der Waals heterostructure | Artificial van der Waals heterostructures, obtained by stacking layered two-dimensional materials, represent a novel material platform for investigating physicochemical phenomena and applications. Here, the electrochemistry at the one-dimensional edge of a graphene sheet, which is sandwiched between two hexagonal boron nitride (hBN) multilayer flakes, is reported. When such an hBN/graphene/hBN heterostructure is immersed in a solution, the basal plane of graphene is protected and isolated by the hBN stack, and the edge of the graphene sheet is exclusively available in the solution. This forms an electrochemical nanoelectrode, which enabled the investigation of electron transfer using several redox probes, e.g., ferrocene(di)methanol, hexaammineruthenium, methylene blue, dopamine and ferrocyanide. The relatively low capacitance of the van der Waals edge electrode facilitates cyclic voltammetry at very high scan rates (up to 1000 V/s). Using fast scan cyclic voltammetry imaging, redox species could be detected voltammetrically down to micromolar concentrations with sub-second time resolution at the sandwiched graphene edge, promoted by the rapid equilibration of analyte species in the diffusion layer. Furthermore, the nanoband nature of the edge electrode allows its operation directly in water in the absence of added electrolyte. Finally, two adjacent edge electrodes could be realized in a redox-cycling format. In all, the van der Waals edge electrode is unique among nanoelectrodes as it enables investigations of all the above-mentioned phenomena in the same device. Due to its versatility, it constitutes a new avenue for nanoscale electrochemistry, which will be useful for studying electron transfer mechanisms as well as for the detection of analyte species in ultralow sample volumes. | Aleksandra Plačkić; Tilmann J Neubert; Kishan Patel; Michel Kuhl; Kenji Watanabe; Takashi Taniguchi; Amaia Zurutuza; Roman Sordan; Kannan Balasubramanian | Materials Science; Analytical Chemistry; Nanoscience; Carbon-based Materials; Electrochemical Analysis; Nanofabrication | CC BY NC ND 4.0 | CHEMRXIV | 2023-07-25 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/64bee6e5ae3d1a7b0d46b3a0/original/electrochemistry-at-the-edge-of-a-van-der-waals-heterostructure.pdf |
6673e7585101a2ffa807f028 | 10.26434/chemrxiv-2024-9928b | A unified photocatalytic strategy for the cross coupling of alcohols with aryl halides enabled by synergistic nickel and iron LMCT catalysis | The use of alcohol feedstock as coupling partner in cross coupling reactions offers an extraordinary potential for the effi-cient synthesis of Csp3-rich complex molecular scaffolds. This prominent strategy relies on the generation of alkoxy radicals, which can react via various radical pathways to give carbon-centered radicals that can be engaged in C-C bond formation reactions. However, cross-coupling reactions involving catalytic generation of alkoxy radicals directly from native alcohols is highly challenging and the scope of existing catalytic methods remains particularly limited. Moreover, a unified strategy that can incorporate a broad range of alcohols in catalytic cross-coupling with aryl halides is currently unavailable. Herein, we report a general photocatalytic platform that combines nickel and iron ligand-to-metal charge transfer (LMCT) catalysis for the selective deconstructive Csp2-Csp3 bond cleavage and arylation of various unactivated alcohols. This protocol lever-ages the ability of photoinduced iron LMCT catalysis to generate radicals from diversely substituted alcohols, enabling im-plementation of various C-C bond-forming manifolds. These include dehydroxymethylative arylation of aliphatic alcohols, remote arylation of cyclic alcohols to yield alkyl ketones, and unprecedented use of tertiary alcohols for methylation of aryl halides. This methodology offers a practical and unified strategy for engaging a large variety of commercially available alcohols in cross-coupling reactions under mild conditions, using abundant nickel and iron catalysts. Mechanistic studies, including stoichiometric organometallic chemistry and cyclic voltammetry, provide unprecedented insights into the crucial role of the ancillary ligand surrounding the iron catalyst in stabilizing high-valent photo-catalytically active intermediates. | Mohammad Jaber; Yasemin Ozbay; Gaël Tran; Abderrahmane Amgoune | Organic Chemistry; Catalysis; Organometallic Chemistry; Organic Synthesis and Reactions; Homogeneous Catalysis; Kinetics and Mechanism - Organometallic Reactions | CC BY NC ND 4.0 | CHEMRXIV | 2024-06-20 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/6673e7585101a2ffa807f028/original/a-unified-photocatalytic-strategy-for-the-cross-coupling-of-alcohols-with-aryl-halides-enabled-by-synergistic-nickel-and-iron-lmct-catalysis.pdf |
626a924cbdc9c20521e5f293 | 10.26434/chemrxiv-2022-brnzv | Spectral Trends in GC-EI-MS Data Obtained from the SWGDRUG Library and Literature: A Resource for the Identification of Unknown Compounds | Rapid identification of new or emerging psychoactive substances remains a critical challenge in forensic drug chemistry laboratories. Current analytical protocols are well-designed for confirmation of known substances yet struggle when new compounds are encountered. Many laboratories initially attempt to classify new compounds using gas chromatography mass spectrometry (GC-MS) data. Though there is a large body of research focused on analysis of illicit substances with GC-MS, there is little high-level discussion of mass spectral trends for different classes of drugs. This manuscript compiles literature information and performs simple exploratory analyses on evaluated GC-MS data to investigate trends of electron ionization (EI) mass spectra on the most reported illicit substance classes. Additionally, this work offers other important aspects: brief discussions of how each class of drugs is used; descriptions of proposed fragmentation pathways of commonly observed ions in EI-MS data; and summaries of mass spectral trends that can help an analyst classify new illicit compounds. | William Feeney; Arun Moorthy; Edward Sisco | Analytical Chemistry; Analytical Chemistry - General; Mass Spectrometry | CC BY NC ND 4.0 | CHEMRXIV | 2022-05-02 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/626a924cbdc9c20521e5f293/original/spectral-trends-in-gc-ei-ms-data-obtained-from-the-swgdrug-library-and-literature-a-resource-for-the-identification-of-unknown-compounds.pdf |
60c746409abda2147ff8c704 | 10.26434/chemrxiv.11259437.v1 | Toward an Optical and Electrochemical Method for Marijuana Detection: A Simple Electrochemical Oxidation of Δ9-THC | Marijuana has long remained one of the most commonly used illicit drugs in the United States and other countries. Recently, it has been estimated that 55 million Americans use this psychoactive drug, with growing usage being attributed to the legalization of marijuana in several states. A concerning implication of increased marijuana use is the alarming number of individuals who report driving under the influence of the drug. It is estimated that nearly 12 million people in the US alone have driven a vehicle while being under the influence of marijuana. To counterbalance the growing use of marijuana and potential associated dangers, it is imperative to develop detection technologies for marijuana usage. An electrochemical-based detection technology, akin to the alcohol breathalyzer, would provide an attractive solution to this growing societal problem. The first step toward this goal is to develop a fundamental reaction that converts tetrahydrocannabinol (THC), the primary psychoactive substance in marijuana, to a derivative with diagnostic spectroscopic changes. We report the development of a mild electrochemical method for the oxidation of THC to its corresponding <i>p</i>-quinone isomer. The photophysical and electrochemical properties of the resultant quinone show a dramatic shift in comparison to THC. This exceedingly simple protocol provides a foundational step toward the development of an electrochemical-based marijuana breathalyzer. | Evan Darzi; Neil Garg | Organic Compounds and Functional Groups | CC BY NC ND 4.0 | CHEMRXIV | 2019-12-03 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/60c746409abda2147ff8c704/original/toward-an-optical-and-electrochemical-method-for-marijuana-detection-a-simple-electrochemical-oxidation-of-9-thc.pdf |
643d0e2a1d262d40eaa0f373 | 10.26434/chemrxiv-2023-2lwsh-v2 | Interpretable attribution assignment for octanol-water partition coefficient | With the increasing development of machine learning models, their credibility has become an important issue. In chemistry, attribution assignment is gaining relevance in designing molecules and debugging models. However, attention has been paid to which atoms are important in the prediction without considering whether the attribution is reasonable. In this study, we developed a graph neural network model, a high interpretable attribution model in chemistry, and modified the integrated gradients method. The credibility of our approach was confirmed by predicting the octanol--water partition coefficient (logP) and evaluating the three metrics --accuracy, consistency, and stability-- in the attribution assignment. | Daisuke Yokogawa; Kayo Suda | Theoretical and Computational Chemistry; Machine Learning | CC BY NC ND 4.0 | CHEMRXIV | 2023-04-19 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/643d0e2a1d262d40eaa0f373/original/interpretable-attribution-assignment-for-octanol-water-partition-coefficient.pdf |
66a258d901103d79c5a8e5d5 | 10.26434/chemrxiv-2024-8qj17 | Generation of Dual-Target Compounds Using a Transformer Chemical Language Model | Compounds with defined multi-target activity are candidates for the treatment of multi-factorial diseases. Such compounds are mostly discovered experimentally, for example, by multi-stage screening campaigns or target profiling. However, multi-target compounds are also topical in drug design. In medicinal chemistry, design of compounds with desired activity against two targets is typically attempted by pharmacophore fusion. In addition, machine learning models can be constructed for multi-task (target) prediction or virtually screening of compound libraries against arrays of single-target classifiers (computational target profiling). Furthermore, multi-target compounds can also be predicted by deep generative modeling. However, compared to pharmacophore approaches and classification models, generative design of multi-target compounds is still in its very early stages. Herein, we introduce transformer-based chemical language model variants for the design of dual-target compounds. Alternative models were pre-trained by learning mappings of single- to dual-target compounds of increasing similarity. Then, different models were optimized for generating compounds with defined activity against pairs of functionally unrelated targets using a new technique termed cross fine-tuning, applying compound similarity constraints corresponding to pre-training. Control models were devised to confirm that pre-trained and fine-tuned models indeed charted chemical space of dual-target compounds. As a stringent criterion for predictive performance, the final models were found to exactly reproduce known dual-target compounds excluded from model derivation. In addition, many structural analogues of such compounds were generated, thus lending credence to the design approach. | Sanjana Srinivasan; Jürgen Bajorath | Biological and Medicinal Chemistry | CC BY NC ND 4.0 | CHEMRXIV | 2024-07-26 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/66a258d901103d79c5a8e5d5/original/generation-of-dual-target-compounds-using-a-transformer-chemical-language-model.pdf |
60c7508eee301c63abc7a8b9 | 10.26434/chemrxiv.13055795.v1 | An Affordable Option to Au Single Crystals Through Cathodic Corrosion of a Wire: Fabrication, Electrochemical Behavior, and Applications in Electrocatalysis and Spectroscopy | Faceting and nanostructuring of polycrystalline gold electrodes by cathodic corrosion in concentrated potassium hydroxide electrolytes has been systematically studied at different electrode potentials. Current-potential curves for the restructured Au electrodes in 0.1 M H2SO4 show characteristic features of Au(111) facets in the double-layer and oxidation region. Thus, the modified Au electrodes adopt properties typically known for well-defined single crystal surfaces. Besides the preferential surface faceting, the electrochemically active surface area (EASA) is enhanced as a function of potential, concentration and time. Scanning electron micrographs show the formation of well-defined triangular pits and nanostructures with a specific orientation confirming the formation of (111)-facets. In this way, the behavior of single crystals is accompanied with the properties of nanoparticles which are of utmost interest in electrocatalysis and surface enhanced Raman spectroscopy (SERS). The electrocatalytic activity of the newly formed “Au(111)” surface from an Au wire has been tested towards the hydrogen evolution reaction (HER) and for the formic acid oxidation reaction (FAOR). The study of electrocatalytic reactions at these nanostructured electrodes allows to identify active centers, which are absent for extended single crystal surfaces. Adsorbed pyridine on the nanostructured Au electrodes directly shows SERS activity, while untreated polycrystalline Au is SERS-inactive. The use of cathodic corrosion of simple wires is a paradigm of SERS-applications in electrochemistry with clean Au electrodes that provide properties of Au(111) single crystals. | Mohamed Elnagar; Johannes M. Hermann; Timo Jacob; Ludwig A. Kibler | Catalysts; Nanostructured Materials - Materials; Materials Chemistry | CC BY NC ND 4.0 | CHEMRXIV | 2020-10-06 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/60c7508eee301c63abc7a8b9/original/an-affordable-option-to-au-single-crystals-through-cathodic-corrosion-of-a-wire-fabrication-electrochemical-behavior-and-applications-in-electrocatalysis-and-spectroscopy.pdf |
64810c83be16ad5c579ead50 | 10.26434/chemrxiv-2023-xzrnb | Synthesis of clean hydrogen gas from waste plastic at zero net cost | Hydrogen gas (H2) is the primary storable fuel for pollution-free energy production, with over 90 million tonnes used globally per year. More than 95% of H2 is synthesized through metal-catalyzed steam methane reforming that produces 11 tonnes of CO2 per tonne H2. “Green H2” from water electrolysis using renewable energy produces sub-stoichiometric CO2, but costs 2-3x more, making it presently economically unviable. Here we report catalyst-free conversion of waste plastic into clean “flash H2” along with high purity graphene. The scalable procedure evolves no CO2 when deconstructing polyolefins and produces H2 in purities up to 94% at high mass yields. Sale of the graphene byproduct at just 5% of its current value yields H2 production at negative cost. Life-cycle assessment demonstrates a 39-84% reduction in emissions compared to other H2 production methods, suggesting the flash H2 process to be an economically viable, clean H2 production route. | Kevin Wyss; Karla Silva; Ksenia Bets; Wala Algozeeb; Carter Kittrell; Carolyn Teng; ChiHun Choi; Weiyin Chen; Jacob Beckham; Boris Yakobson; James Tour | Energy; Fuels - Energy Science | CC BY NC ND 4.0 | CHEMRXIV | 2023-06-08 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/64810c83be16ad5c579ead50/original/synthesis-of-clean-hydrogen-gas-from-waste-plastic-at-zero-net-cost.pdf |
64a5d9c8ba3e99daef95e4d5 | 10.26434/chemrxiv-2023-97041 | A Prodigious Behavior of Cycloalkyl Carboxylic Acid to Access 2D Space from 3D Space via Multifold C-H Activation | The dehydrogenation chemistry has long prevailed in the paradigm of organic synthesis. More common with carbonyl compounds, many classical reactions evolved around it. The emergence of the transition metal catalysis redefined the dehydrogenation chemistry with strategies such as transfer dehydrogenation, C-H activation and single electron transfer processes. These strategies have been extended to enable multiple dehydrogenations that had led to aromatization depending on the substrate class. On a contrary, dehydrogenative transformations of aliphatic carboxylic acids offers substantial challenges. Engineered ligands in conjunction with metal catalysis can effectuate the dehydrogenation in carboxylic acids initiated by C-H activation with subsequent functionalization or vice versa; however, the reactivity and product formation vary with the substrate structure. Herein, we have developed a catalytic system that enables cyclohexane carboxylic acid to undergo multifold C-H activation to furnish olefinated arenes implying 3D to 2D conversion and thus, completely bypassing the lactone formation, showcasing a display of the change in reactivity of aliphatic carboxylic acids. The reaction occurs via a tandem dehydrogenation-olefination-decarboxylation-aromatization sequence which has been proved by various control experiments and isolation of key intermediates. For cyclopentane carboxylic acid which are reluctant to aromatization, the same catalytic system allows controlled dehydrogenation to provide difunctionalized cyclopentene derivatives via a tandem dehydrogenation-olefination-decarboxylation-allylic acyloxylation reaction sequence. The transformation is amenable to diversify carboxylic acids to be transformed to molecules of new identity having applications in different fields thus underscoring the im-portance. | Debabrata Maiti; Tanay Pal; Premananda Ghosh; Minhajul Islam; Srimanta Guin; Suman Maji; Suparna Dutta; Jayabrata Das; Haibo Ge | Organic Chemistry; Catalysis; Organometallic Chemistry; Organic Synthesis and Reactions; Bond Activation; Catalysis | CC BY NC ND 4.0 | CHEMRXIV | 2023-07-06 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/64a5d9c8ba3e99daef95e4d5/original/a-prodigious-behavior-of-cycloalkyl-carboxylic-acid-to-access-2d-space-from-3d-space-via-multifold-c-h-activation.pdf |
6177bd06913a742b636afc83 | 10.26434/chemrxiv-2021-j7qj2 | Crystal-chemical and biological controls of trace and minor element incorporation into magnetite nanocrystals | Magnetite nanoparticles possess numerous fundamental, biomedical and industrial applications, many of which depend on tuning the magnetic properties. This is often achieved by the incorporation of trace and minor elements into the magnetite lattice. Such incorporation was shown to depend strongly on the magnetite formation pathway (i.e., abiotic vs biological), but the mechanisms controlling element partitioning between magnetite and its surrounding precipitation solution remain to be elucidated. Here, we used a combination of theoretical modelling (lattice and crystal field theories) and experimental evidence (high-resolution inductively coupled plasma mass spectrometry and X-ray absorption spectroscopy) to demonstrate that element incorporation into abiotic magnetite nanoparticles is controlled principally by cation size and valence. Elements from the first series of transition metals (Cr to Zn) constituted exceptions to this finding as their incorporation appeared to be also controlled by the energy levels of their unfilled 3d orbitals, in line with crystal field mechanisms. We then show that element incorporation into biological magnetite nanoparticles produced by magnetotactic bacteria (MTB) cannot be explained by crystal-chemical parameters alone, which points to the biological control exerted by the bacteria over the element transfer between MTB growth medium and the intracellular environment. This screening effect generates biological magnetite with a purer chemical composition than the abiotic materials formed in a solution of similar composition. Our work establishes a theoretical framework for understanding the crystal-chemical and biological controls of trace and minor cation incorporation into magnetite, thereby providing predictive methods to tailor the composition of magnetite nanoparticles for improved control over magnetic properties. | Matthieu Amor; Damien Faivre; Daniel M. Chevrier | Physical Chemistry; Materials Science; Nanoscience; Magnetic Materials; Nanostructured Materials - Materials | CC BY NC ND 4.0 | CHEMRXIV | 2021-10-26 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/6177bd06913a742b636afc83/original/crystal-chemical-and-biological-controls-of-trace-and-minor-element-incorporation-into-magnetite-nanocrystals.pdf |
65524ee12c3c11ed71514842 | 10.26434/chemrxiv-2023-v9841-v2 | DELFI: A computer oracle for recommending density functionals for excited states calculations | Density functional theory (DFT) is known as the workhorse of computational quantum chemistry. One of its main limitations, if not the main one, is that choosing the right functional to employ is a non-trivial task left for human experts. The choice is particularly hard for excited states calculations, when using the time-dependent formulation of DFT (TD-DFT). This is not only due to the approximations and limitations of the method, but also because the photophysical properties of a molecule are defined by a manifold of states that all need to be properly described in a balanced manner to obtain an accurate photochemical picture. This includes not only the relative energy of the states, but also capturing the correct character, order and intensity of the transitions. In this work, we developed a scoring system to quantitatively define the accuracy of an excited states calculation by simultaneously considering at the same time all these properties of a manifold of states. The scoring system is generalizable to any level of theory, we here applied it to a large dataset of organic molecules, calculating 38 scores for as many common functionals of different type and rung, against a higher accuracy method for a total of more than 820.000 single point calculations. The results of these calculations are collected in a database that we released and made it open, providing 4 million datapoints to be used by the community for future applications. We used the scores we extrapolated to train a graph attention neural network that is used to predict the 38 scores for molecules represented as 2D graphs. We call this oracle DELFI (Data-driven EvaLuation of Functionals by Inference), which can be used to quickly screen and predict the ranking of functionals to calculate optical properties of organic molecules. A corresponding web application allows to easily run DELFI and analyze the results, alleviating the hurdle of choosing the right functional for TD-DFT calculations. | Davide Avagliano; Marta Skreta; Sebastian Arellano-Rubach; Alán Aspuru-Guzik | Theoretical and Computational Chemistry; Computational Chemistry and Modeling; Theory - Computational; Machine Learning | CC BY 4.0 | CHEMRXIV | 2023-11-15 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/65524ee12c3c11ed71514842/original/delfi-a-computer-oracle-for-recommending-density-functionals-for-excited-states-calculations.pdf |
61e504edf2bef7b8b6a46184 | 10.26434/chemrxiv-2022-20s93 | An infectious virus-like particle built on a programmable icosahedral DNA framework | Viral genomes can be compressed into a near spherical nanochamber to form infected particles. In order to mimic the virus morphology and packaging behavior, we invented a programmable icosahedral DNA nanoframe with enhanced rigidity and encapsulated the phiX174 bacteriophage genome. The packaging efficiency could be modulated through specific anchoring strands adjustment, and the enveloped phage genome remained accessible for enzymatic operations. Moreover, the packed complex could infect E. coli cells through bacterial uptake then produce plaques. This rigid icosahedral DNA architecture established a versatile platform to develop virus mimetic particles for convenient nucleic acid entrapment, manipulation and delivery. | Yang Yang; Yunyun Xu; Yuhe Yang; Qian Shi; Andrew Ward; Wei Wang | Biological and Medicinal Chemistry; Nanoscience; Nanodevices; Chemical Biology | CC BY NC ND 4.0 | CHEMRXIV | 2022-01-17 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/61e504edf2bef7b8b6a46184/original/an-infectious-virus-like-particle-built-on-a-programmable-icosahedral-dna-framework.pdf |
618020ea7a002116c2429a34 | 10.26434/chemrxiv-2021-rb933 | Reviving the Coordination Chemistry of Sulfonium Cations | ABSTRACT: More than a century old, sulfonium ions are still intriguing species in the landscape of organic chemistry. On one hand they have found broad applications in organic synthesis and material science, but on the other hand, while isoelectronic to the ubiquitous tertiary phosphine ligands, their own coordination chemistry has been neglected for the last three decades. Here we report the synthesis and full characterization of the first Rh(I) and Pt(II) complexes of sul-fonium. Moreover, for the first time, the coordinating ability of an aromatic sulfonium has been established. A thorough computational analysis of the exceptionally short S-Rh bonds obtained attests for the strongly π-accepting nature of sul-fonium cations and places them among the best π-acceptor ligands available today. Our calculations also show that when embedded within a pincer framework their π-acidity is enhanced. Therefore, in addition to the stability and modularity that these frameworks offer, our pincer complexes might open the way for sulfonium cations to become powerful tools in π-acid catalysis. | Ruiping Li; Nitsan Barel; Vasudevan Subramaniyan; Orit Cohen; Francoise Tibika; Yuri Tulchinsky | Inorganic Chemistry; Organometallic Chemistry; Ligand Design; Main Group Chemistry (Organomet.); Transition Metal Complexes (Organomet.) | CC BY NC ND 4.0 | CHEMRXIV | 2021-11-08 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/618020ea7a002116c2429a34/original/reviving-the-coordination-chemistry-of-sulfonium-cations.pdf |
64ae799c6e1c4c986b422166 | 10.26434/chemrxiv-2023-rt8kr | A semi-automated, high-throughput approach for the synthesis and identification of highly photo-cytotoxic iridium complexes | The discovery of new compounds with pharmacological properties is usually a lengthy, laborious and expensive process. Thus, there is increasing interest in developing workflows that allow for the rapid synthesis and evaluation of libraries of compounds with the aim of identifying leads for further drug development. Herein we report on such a workflow for the synthesis and evaluation of libraries of over 80 iridium(III) complexes as phototoxic agents against cancer cells. We demonstrate that it is possible to complete the whole semiautomated workflow within 72 hours, allowing for rapid library iteration. This includes all steps from the synthesis of a library of new complexes and their characterisation, to determining their cellular uptake, localisation and phototoxicity. We demonstrate the power of this rapid synthesise-and-test cycle by identifying highly active complexes which are well-tolerated in the dark but display phototoxicity at very low nM concentrations against cancer cells. | Ramon Vilar; Timothy Kench; Arielle Rahardjo; Adinarayana Bellamkonda; Thomas E. Maher; Marko Storch | Biological and Medicinal Chemistry; Inorganic Chemistry; Organometallic Chemistry; Drug Discovery and Drug Delivery Systems; Bioorganometallic Chemistry; Coordination Chemistry (Organomet.) | CC BY NC ND 4.0 | CHEMRXIV | 2023-07-13 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/64ae799c6e1c4c986b422166/original/a-semi-automated-high-throughput-approach-for-the-synthesis-and-identification-of-highly-photo-cytotoxic-iridium-complexes.pdf |
67806e0281d2151a02879c35 | 10.26434/chemrxiv-2025-vz1c5 | Isayama–Mukaiyama Peroxidation Eschews Ozonolysis in Hydrodealkenylation | Advancements in radical capture strategies have expanded the range of products accessible from alkenes through dealkenylative synthesis. These methods, however, are still limited, as they rely on ozonolysis to generate the key peroxide intermediates from alkenes. Ozonolysis has specific limitations: it is incompatible with alkenes containing electronrich aromatics, unproductive alkene substitution patterns, sterically hindered alkenes, internal nucleophiles and electrophiles, and allylic alcohols. In this paper, using Isayama–Mukaiyama peroxidation (IMP), we address the limitations of ozonolysis to rescue previously inaccessible alkene substrates and broaden the applicability of dealkenylative functionalization. In addition, we describe a novel reductive hydrogenation—employing catalytic [FeIII], catalytic benzenethiol, and γ-terpinene in refluxing methanol—to resolve β-scission issues associated with IMP-generated alkyl silylperoxides. | Ohyun Kwon; Jeremy Dworkin; Zhuoxi Chen; Kathleen Cheasty; Aris Rubio | Organic Chemistry; Catalysis; Natural Products; Organic Synthesis and Reactions; Redox Catalysis | CC BY NC ND 4.0 | CHEMRXIV | 2025-01-13 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/67806e0281d2151a02879c35/original/isayama-mukaiyama-peroxidation-eschews-ozonolysis-in-hydrodealkenylation.pdf |
60c7404f469df49930f42bfc | 10.26434/chemrxiv.7691933.v1 | Mixed-Carbene Cyclometalated Iridium Complexes with Saturated Blue Luminescence | This work describes the synthesis and photoluminescence of new heteroleptic mixed-carbene cyclometalated iridium complexes. Complexes are synthesized via a nucleophilic addition cascade reaction with isocyanide-bound precursors. The steady-state and time-resolved photoluminescence properties of the compounds are measured, both in solution and in poly(methyl methacrylate) (PMMA) thin films. Full experimental details are given in the main text and supporting information.<br /> | Hanah Na; Louise Cañada; Thomas Teets | Organometallic Compounds; Coordination Chemistry (Organomet.); Ligand Design; Spectroscopy (Organomet.); Photochemistry (Physical Chem.) | CC BY NC ND 4.0 | CHEMRXIV | 2019-02-08 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/60c7404f469df49930f42bfc/original/mixed-carbene-cyclometalated-iridium-complexes-with-saturated-blue-luminescence.pdf |
60c745b5469df41fbaf43535 | 10.26434/chemrxiv.10113128.v1 | Enhancing Binding Affinity of an Intrinsically Disordered Protein by α-Methylation of Key Amino Acid Residues | Intrinsically disordered proteins (IDPs), which undergo folding upon binding to their targets, are critical players in protein interaction networks. Here we demonstrate that incorporation of non-canonical alpha-methylated amino acids into the unstructured activation domain of the transcriptional coactivator ACTR can stabilize helical conformations and strengthen binding interactions with the nuclear coactivator binding domain (NCBD) of CREB-binding protein (CBP). A combinatorial alpha-methylation scan of the ACTR sequence converged on two substitutions at positions 1055 and 1076 that increase affinity for both NCBD and the full length 270 kDa CBP by one order of magnitude. The first X-ray structure of the modified ACTR domain bound to NCBD revealed that the key alpha-methylated amino acids were localized within alpha-helices. Biophysical studies showed that the observed changes in binding energy are the result of long-range interactions and redistribution of enthalpy and entropy. This proof-of-concept study establishes a potential strategy for selective inhibition of protein-protein interactions involving IDPs in cells.<br /> | Valentin Bauer; Boris Schmidtgall; Gergő Gógl; Jozica Dolenc; Judit Osz; Yves Nominé; Camille Kostmann; Alexandra Cousido-Siah; André Mitschler; Natacha Rochel; Gilles Travé; Bruno Kieffer; Vladimir Torbeev | Biochemistry; Biophysics; Cell and Molecular Biology; Chemical Biology | CC BY NC ND 4.0 | CHEMRXIV | 2019-11-06 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/60c745b5469df41fbaf43535/original/enhancing-binding-affinity-of-an-intrinsically-disordered-protein-by-methylation-of-key-amino-acid-residues.pdf |
6660add5418a5379b02860e8 | 10.26434/chemrxiv-2024-k06gb-v3 | LSM1-MS2: A Foundation Model for MS/MS, Encompassing Chemical Property Predictions, Search and de novo Generation | We present LSM1-MS2, a pre-trained self-supervised foundation model designed for tandem mass spectrometry (MS/MS) utilizing a transformer architecture with custom tokenization for masked MS2 peak reconstruction. Our model is fine-tuned on smaller, labeled datasets for tasks such as compound property prediction, spectral matching, and de novo molecular generation. LSM1-MS2 demonstrates superior performance compared to traditional supervised models, achieving high accuracy with minimal labeled data. It outperforms conventional methods in database lookups and molecular query retrievals and shows promising results in the opening field of de novo molecular generation. The model's efficiency in spectral lookup tasks, with significantly reduced evaluation times, underscores its potential for large-scale applications. Our findings highlight the transformative capability of self-supervised pre-training in enhancing the predictive power of models for mass spectrometry, particularly in data-limited scenarios. The success of LSM1-MS2 in property prediction, database spectral lookup, and molecular generation paves the way for its application in metabolomics and drug discovery, facilitating robust and scalable analysis with reduced data requirements. | Gabriel Asher; Mimoun Cadosh Delmar; Jennifer M. Campbell; Jack Geremia; Timothy Kassis | Analytical Chemistry; Mass Spectrometry | CC BY NC ND 4.0 | CHEMRXIV | 2024-06-06 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/6660add5418a5379b02860e8/original/lsm1-ms2-a-foundation-model-for-ms-ms-encompassing-chemical-property-predictions-search-and-de-novo-generation.pdf |
661e55c721291e5d1df281c8 | 10.26434/chemrxiv-2023-x6tjr-v5 | Benchmarking ML in ADMET predictions: the practical impact of feature representations in ligand-based models | This study, focusing on predicting Absorption, Distribution, Metabolism, Excretion, and Toxicology (ADMET) properties, addresses the key challenges of ML models trained using ligand-based representations. We propose a structured approach to data feature selection, taking a step beyond the conventional practice of combining different representations without systematic reasoning. Additionally, we enhance model evaluation methods by integrating cross-validation with statistical hypothesis testing, adding a layer of reliability to the model assessments. Our final evaluations include a practical scenario, where models trained on one source of data are evaluated on a different one. This approach aims to bolster the reliability of ADMET predictions, providing more dependable and informative model evaluations. | Gintautas Kamuntavičius; Tanya Paquet; Orestis Bastas; Dainius Šalkauskas; Alvaro Prat; Hisham Abdel Aty; Povilas Norvaišas; Roy Tal | Theoretical and Computational Chemistry; Machine Learning; Artificial Intelligence; Chemoinformatics - Computational Chemistry | CC BY NC ND 4.0 | CHEMRXIV | 2024-04-17 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/661e55c721291e5d1df281c8/original/benchmarking-ml-in-admet-predictions-the-practical-impact-of-feature-representations-in-ligand-based-models.pdf |
671ad74598c8527d9e4add6d | 10.26434/chemrxiv-2024-0jv9z-v3 | Towards a Universal Design Principle for Low-Hysteresis High-Valent Redox in Battery Cathodes: Synergizing Cationic Ordered Vacancies with Tunable Metal-Ligand Hybridization | Sodium-ion batteries have the potential to meet the growing demand for energy storage due to
their low costs stemming from natural resource abundances, but their cathode energy densities
must be improved to be comparable to those of lithium-ion batteries. One strategy is accessing
high voltage capacity through high-valent redox reactions. Such reactions usually cause
instability in cathode materials, but Na2Mn3O7 (NMO) has demonstrated excellent performance
and reversibility in the high-valent regime due to its unique lattice structure with ordered Mn
vacancies. This work expands the universality of the ordered vacancy as a design principle and
increases the material candidates with such exceptional electrochemical behavior. Our approach
involves synergizing cationic ordered vacancies with tunable metal-ligand hybridization through
partial metal substitution. In particular, we successfully incorporated Fe3+ for Mn4+ in NMO to
make Na2.25Mn2.75Fe0.25O7 and achieved improved high-valent redox behavior. Fe substitution
leads to larger specific capacities (171 vs 159 mAh/g first cycle), enhanced cycle stability (97 vs
60 mAh/g after 50 cycles), and superior rate performance. This study lays the foundation for
developing new cathode materials with stable high-valent redox through substitution of
redox-active transition metals by employing cationic ordered vacancies and partial transition
metal substitution as design principles in tandem. | Hugh Smith; Gi-Hyeok Lee; Bachu Sravan Kumar; Aubrey Penn; Victor Venturi; Yifan Gao; Ryan Davis; Kevin Stone; Adrian Hunt; Iradwikanari Waluyo; Eli Stavitski; Wanli Yang; Iwnetim Abate | Materials Science; Energy; Energy Storage | CC BY NC 4.0 | CHEMRXIV | 2024-10-25 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/671ad74598c8527d9e4add6d/original/towards-a-universal-design-principle-for-low-hysteresis-high-valent-redox-in-battery-cathodes-synergizing-cationic-ordered-vacancies-with-tunable-metal-ligand-hybridization.pdf |
6483c8c44f8b1884b715bece | 10.26434/chemrxiv-2023-1p1kv-v2 | meta-Selective Radical Acylation of Electron-rich Arenes | meta-Selective functionalisation of electron-rich arenes provides a non-traditional route to organic synthesis. In classical electrophilic aromatic substitution of electron-donating group-pendant arenes, functionalisation occurs according to ortho- and para-orientation. There have been numerous efforts to overcome this selectivity, and various synthetic methods have been developed, mainly based on transition metal catalysis. Here, we show a new N-heterocyclic carbene and organic photoredox cocatalysis for meta-selective acylation of electron-rich arenes. This approach proceeds without the directing groups or steric factors required in transition metal catalysis, resulting in precisely opposite regioselectivity from conventional approaches such as the Friedel–Crafts acylation. The catalytic system involves a sequence of single electron oxidation of an electron-rich arene followed by the radical–radical coupling between a ketyl radical and an arene radical cation. This protocol will lead to the expeditious synthesis of organic molecules that commonly require multiple steps and rare metals and promotes the construction of libraries of biologically active molecules. | Yamato Goto; Masaki Sano; Yuto Sumida; Hirohisa Ohmiya | Organic Chemistry; Catalysis; Organic Synthesis and Reactions; Photocatalysis; Redox Catalysis | CC BY NC ND 4.0 | CHEMRXIV | 2023-06-12 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/6483c8c44f8b1884b715bece/original/meta-selective-radical-acylation-of-electron-rich-arenes.pdf |
60c750cebb8c1a32e83dbb73 | 10.26434/chemrxiv.13077386.v1 | Thermal Ranges and Figures of Merit for Gold-Containing Precursors For ALD | A survey of known gold-containing chemical vapour
deposition (CVD) and atomic layer deposition (ALD) precursors, with a focus on
collecting their volatilization and decomposition data. These data were applied
to a figure of merit (σ) developed to easily
assess the thermal characteristics. | Matthew Griffiths; Zachary Dubrawski; Peter Gordon; Marcel Junige; Sean Barry | Thin Films; Transition Metal Complexes (Inorg.) | CC BY NC ND 4.0 | CHEMRXIV | 2020-10-13 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/60c750cebb8c1a32e83dbb73/original/thermal-ranges-and-figures-of-merit-for-gold-containing-precursors-for-ald.pdf |
678e2d8581d2151a02e47f8f | 10.26434/chemrxiv-2025-r1zlr | Synthesis and characterisation of Li₄(OH)₃Br for thermal energy storage | The peritectic compound Li₄(OH)₃Br has been suggested as a candidate material for latent heat thermal energy storage due to its high calculated melting enthalpy of 804 joules per gram around 300 degrees Celsius. However, experimental reports have obtained much lower values, at or below 250 joules per gram. In this work, we demonstrate that the crystal structure established for Li₄(OH)₃Br in the literature corresponds to a metastable hydrated compound. Instead, we propose that the thermodynamically stable phase belongs to the Pmmn space group. The hydrated phase dehydrates at approximately 175 degrees Celsius, rendering the exceptional previous predictions inapplicable. An experimentally measured melting enthalpy of 263 joules per gram is reported for high-purity Li₄(OH)₃Br. Theoretical modeling suggests a crystal structure for Li₄(OH)₃Br, from which a melting enthalpy of 260 joules per gram is calculated. This result aligns well with the experimental findings and supports that, despite lower-than-expected values, Li₄(OH)₃Br can still offer an impressive storage capacity at around 290 degrees Celsius. | Emily Milan; James A. Quirk; John Cattermull; Andrew L. Goodwin; James A. Dawson; Mauro Pasta | Materials Science; Ceramics; Materials Processing; Materials Chemistry | CC BY NC ND 4.0 | CHEMRXIV | 2025-01-21 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/678e2d8581d2151a02e47f8f/original/synthesis-and-characterisation-of-li4-oh-3br-for-thermal-energy-storage.pdf |
6446a136e4bbbe4bbf2f0de3 | 10.26434/chemrxiv-2023-11691 | Computational Investigations of the Water Structure at α-Al2O3(0001)-Water Interfaces | The α-Al2O3(0001)-water interface is investigated using ab initio molecular dynamics (AIMD) simulations. The spectral signatures of the vibrational sum frequency generation (vSFG) spectra of OH stretching mode for water molecules at the interface was related to the interfacial water orientation, hydrogen bond network, and water dissociation process at different water/alumina interfaces. Significant differences are found between alumina surfaces at different hydroxylation levels, namely, Al-terminated and O-terminated α-Al2O3(0001). By calculating the vibrational sum frequency generation spectra and its imaginary component from AIMD results, the structure of interfacial waters as well as the termination of the alumina slab were related to the spectral signatures of vSFG data. | Xiaoliu Zhang; Christopher Arges; Revati Kumar | Theoretical and Computational Chemistry; Physical Chemistry; Computational Chemistry and Modeling; Interfaces | CC BY NC ND 4.0 | CHEMRXIV | 2023-04-25 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/6446a136e4bbbe4bbf2f0de3/original/computational-investigations-of-the-water-structure-at-al2o3-0001-water-interfaces.pdf |
649b5cf36e1c4c986b7221c7 | 10.26434/chemrxiv-2023-bjmh1 | Dual Photosensitizer Cycles Working Synergistically in a C(sp)-C(sp3) Cross-Coupling Reaction | To assess the value and reactivity of new photocatalysts (PCs), their performance should be evaluated in one or more established reactions and benchmarked against the performance using known PCs. Here, we evaluated our recently developed PC, pDTCz-DPmS, in a C(sp)-C(sp3) cross-coupling reaction that had been documented in the literature. Previous findings indicated this reaction could not proceed in the absence of PC; however, under our conditions this was not the case. Without PC, a moderate product yield was obtained, while this yield increased significantly upon addition of pDTCz-DPmS. UV-Vis absorption studies indicated that the Hantzsch ester (HE) additive was acting as a competitive absorber of the light from the excitation source, and quenching studies confirmed that the HE was quenched by the radical precursor, N-(acyloxy)phthalimide. Mechanistic investigations established that two parallel photosensitization pathways were in operation; a reductive quenching photocatalytic pathway (using pDTCz-DPmS) and a sacrificial photoreductant pathway (employing HE). These pathways work synergistically to enhance the yield of target product. | Megan Bryden; Marco Villa; Andrea Fermi; Paola Ceroni; Eli Zysman-Colman | Organic Chemistry; Photochemistry (Org.) | CC BY 4.0 | CHEMRXIV | 2023-06-29 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/649b5cf36e1c4c986b7221c7/original/dual-photosensitizer-cycles-working-synergistically-in-a-c-sp-c-sp3-cross-coupling-reaction.pdf |
60c746ebbb8c1a5ed63da990 | 10.26434/chemrxiv.11436012.v1 | Highly Mesoporous Carbon Aerogel as Catalyst Support in Proton Exchange Membrane Fuel Cells | <p>Carbon aerogel possesses unique structural and electrical properties, such as high mesopore volume, specific surface area, and electrical conductivity, which make it suitable for use as a catalyst support in Proton Exchange Membrane Fuel Cells (PEMFC). In this study, we present a novel synthesis of highly mesoporous carbon aerogel via ambient-drying and investigate its application in PEMFCs. The structural effects of activation on carbon aerogel were also studied. The TEM, XRF, Non Localized Density Function Theory (NLDFT) and BJH analysis were carried out to observe the morphology and pore structure. Pt on carbon aerogel and activated carbon aerogel show efficient activity in both oxygen reduction and hydrogen oxidation reactions compared to Pt on Vulcan XC-72, with increases up to 715% and 195% in specific power density, respectively. The enhanced performance of carbon aerogel is attributed to its large specific surface area and high mesopore to micropore ratio. Accelerated stress tests show that carbon aerogel has comparable durability with Vulcan XC-72, while activated carbon aerogel is less durable than both materials. Thus, the mesoporous carbon aerogel provides an efficient, lower-cost alternative to existing microporous carbon material as a catalyst support in PEMFCs.</p><p></p> | Kevin Gu; Eric J. Kim; Sunil K. Sharma; Miriam Rafailovich | Carbon-based Materials; Electrocatalysis | CC BY NC ND 4.0 | CHEMRXIV | 2019-12-24 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/60c746ebbb8c1a5ed63da990/original/highly-mesoporous-carbon-aerogel-as-catalyst-support-in-proton-exchange-membrane-fuel-cells.pdf |
60c743b19abda2dc91f8c21d | 10.26434/chemrxiv.9491261.v1 | Symmetry Breakdown in Franckeite: Spontaneous Strain, Rippling and Interlayer Moiré | <p>Franckeite is a naturally occurring layered mineral with a structure
composed of alternating stacks of SnS<sub>2</sub>-like and PbS-like layers. Although
this superlattice is composed of a sequence of isotropic two-dimensional
layers, it exhibits a spontaneous rippling that makes the material structurally
anisotropic. We demonstrate that this rippling comes hand in hand with an
inhomogeneous in-plane strain profile and anisotropic electrical, vibrational
and optical properties. We argue that this symmetry breakdown results from a
spatial modulation of the van der Waals interaction between layers due to the
SnS<sub>2</sub>-like and PbS-like lattices incommensurability.</p> | Riccardo Frisenda; Gabriel Sanchez-Santolino; Nikos Papadopoulos; Joanna Urban; Michal Baranowski; Alessandro Surrente; Duncan K. Maude; Mar Garcia-Hernandez; Herre S.J. van der Zant; Paulina Plochocka; Pablo San-Jose; Andres Castellanos-Gomez | Nanostructured Materials - Nanoscience | CC BY NC ND 4.0 | CHEMRXIV | 2019-08-13 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/60c743b19abda2dc91f8c21d/original/symmetry-breakdown-in-franckeite-spontaneous-strain-rippling-and-interlayer-moire.pdf |
632ae185975e94a624832c9a | 10.26434/chemrxiv-2022-s6fxg-v2 | Fast and cost-efficient approaches for 17O-isotopic labeling of carboxylic groups in biomolecules: from free amino acids to peptide chains | 17O NMR spectroscopy is a powerful analytical technique, which enables to access unique information regarding the structure and reactivity of biomolecules, such as peptides and proteins. However, due to the exceedingly low natural abundance of 17O (0.04 %), it is necessary to work with 17O-enriched samples, which are not easily accessible because of the experimental constraints and high costs associated with the traditional enrichment procedures. Here, we present simple, fast and cost-efficient labeling strategies for 17O-enrichment of amino acids and peptides. First, using mechanochemical saponification, a variety of unprotected amino acids were enriched within 30 min of milling under ambient conditions, consuming only microliter amounts of costly labeled water, and producing pure molecules with high enrichment levels (up to ~ 40 %), and in medium to high yields (~ 60 - 85 %) without the loss of their optical purity (ee > 99%). The labeling efficiency of the mechanochemical protocol was then compared to a re-optimised enrichment strategy based on acid-catalysed oxygen exchange. Subsequently, 17O-enriched Fmoc/tBu-protected amino acids were produced on a 1 g/day scale with high enrichment levels (~ 40 %), and in high synthetic yields (~ 75 - 85 %), by scaling up the mechanochemical enrichment followed by a Fmoc-protection step. Lastly, a direct site-selective 17O-labeling of carboxylic functions in peptide side-chains was developed and applied to the RGD and GRGDS peptides, reaching up to 29% enrichment level. Producing highly enriched molecules enabled to record 17O solid-state NMR spectra at 14.1 T in reasonable analytical times. Overall, this work represents an important step forward in providing easy access to highly 17O-enriched peptides and proteins to be subsequently studied by high-resolution 17O NMR spectroscopy. | Jessica Špačková; Ieva Goldberga; Rishit Yadav; Guillaume Cazals; Aurélien Lebrun; Pascal Verdié; Thomas-Xavier Métro; Danielle Laurencin | Organic Chemistry; Analytical Chemistry; Organic Synthesis and Reactions; Spectroscopy (Anal. Chem.) | CC BY NC ND 4.0 | CHEMRXIV | 2022-09-21 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/632ae185975e94a624832c9a/original/fast-and-cost-efficient-approaches-for-17o-isotopic-labeling-of-carboxylic-groups-in-biomolecules-from-free-amino-acids-to-peptide-chains.pdf |
63528561cf6de90daf1c2fc8 | 10.26434/chemrxiv-2022-kkcth | Trithiolato-Bridged Dinuclear Arene Ruthenium(ll)- Glycoconjugates: Synthesis and Antiparasitic Activity | Eight novel carbohydrate-tethered trithiolato dinuclear ruthenium(II)-arene complexes were synthesized using CuAAC 'click' (Cu(I)-catalyzed azide-alkyne cycloaddition) reactions and, together with the diruthenium intermediates, were assessed for their in vitro activity against transgenic Toxoplasma gondii (T. gondii) tachyzoites constitutively expressing β-galactosidase (T. gondii β-gal), and for their cytotoxicity in non-infected host cells (human foreskin fibroblasts, HFFs). The results revealed that the biological activity of the hybrids was influenced by both the nature of the carbohydrate (glucose or galactose) attached to the ruthenium complex and the type/length of the linker between the two units. For seven selected diruthenium-carbohydrate conjugates, the values of the half-maximal inhibitory concentration (IC50) on T. gondii β-gal and HFFs viability for a compound concentration of 2.5 μM were measured. Remarkably, two galactose-diruthenium conjugates, 23 and 26, performed significantly better than the corresponding unlabeled diruthenium complexes and the standard drug Pyrimethamine, with very low IC50 values (23: IC50 = 0.032 μM, 26: IC50 = 0.153 μM, Pyrimethamine, IC50 = 0.326 μM) and a very low toxicity on HFFs (viability 92% for 23 and 97% for 26). Overall, our study shows that conjugation of carbohydrates to diruthenium compounds is a promising approach to develop new effective antiparasitic compounds with reduced toxicity. | Isabelle Holzer; Oksana Desiatkina; Nicoleta Anghel; Serena K. Johns; Ghalia Boubaker; Andrew Hemphill; julien Furrer; Emilia Paunescu | Inorganic Chemistry; Bioinorganic Chemistry | CC BY 4.0 | CHEMRXIV | 2022-10-25 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/63528561cf6de90daf1c2fc8/original/trithiolato-bridged-dinuclear-arene-ruthenium-ll-glycoconjugates-synthesis-and-antiparasitic-activity.pdf |
6238d9bf658bc08f17b3482c | 10.26434/chemrxiv-2022-1lkkx | Installation of cysteine-derived methyllysine mimics on phage-dis- played peptide libraries: optimization of reaction conditions for conversion and phage viability | We report a synthetic methodology for the installation of methyllysine mimics on cysteine-containing peptides and bacteriophage peptide libraries. Strategies that allow for diversity and high throughput screening of PTM-containing peptides are critical for successfully targeting the many methyllysine reader proteins that are misregulated in cancer and disease. We have de- veloped conditions for alkylation of cysteine containing peptides with (2-haloethyl) amines, providing products that closely mimic methyllysine residues. Extensive optimization on C7C peptide phage constructs allowed for the successful installation of Kme3 mimics in 60–70% yields to create post-translational ε-Lys-N-methylated peptide phage libraries. Optimized reaction conditions between 2-bromo-N,N,N-trimethylethaninium bromide and commercially available PhD C7C library produce >2 × 1011 phage parti- cles and libraries of ~2 × 108 diversity in which each peptide sequence contains the Kme3 mimic. This process adds a new fragment into readily available genetically encoded libraries and opens new avenues for high throughput screening that may give rise to new ligands for a variety of methyllysine reader proteins. | Natalia Milosevich; Katrina H. Vizely; Roko P.A. Nikolic; Jacob F. McCallum; Lee M. Treanor; Sarah S. Khan; Ratmir Derda; Fraser Hof | Biological and Medicinal Chemistry; Organic Chemistry; Bioorganic Chemistry; Organic Synthesis and Reactions; Chemical Biology | CC BY NC ND 4.0 | CHEMRXIV | 2022-03-22 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/6238d9bf658bc08f17b3482c/original/installation-of-cysteine-derived-methyllysine-mimics-on-phage-dis-played-peptide-libraries-optimization-of-reaction-conditions-for-conversion-and-phage-viability.pdf |
62ed85d704c85f53ad8533eb | 10.26434/chemrxiv-2022-cn0k1 | Efforts to Develop a Cost-Effective and Scalable Synthetic Process for Nirmatrelvir | Nirmatrelvir, the novel antiviral component of Pfizer’s orally available combination therapy Paxlovid, used to treat COVID-19, presents a significant synthetic challenge. Herein, we report process optimization insights that could enable a scalable and cost-effective manufacturing process to make nirmatrelvir. The disclosed development opens up a path to three new complete routes, offering options to eliminate some of the major cost-drivers for nirmatrelvir and deliver the final API in higher yield and lower overall cost while maintaining quality requirements. | Charles S. Shanahan; Appasaheb L. Kadam; Barreddi Chiranjeevi; Aline A. Nunes; Aravindan Jayaraman; Saeed Ahmad; Sarah L. Aleshire; Kai O. Donsbach; B. Frank Gupton; Michel C. Nuckols | Organic Chemistry; Organic Compounds and Functional Groups; Organic Synthesis and Reactions; Process Chemistry | CC BY NC ND 4.0 | CHEMRXIV | 2022-08-08 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/62ed85d704c85f53ad8533eb/original/efforts-to-develop-a-cost-effective-and-scalable-synthetic-process-for-nirmatrelvir.pdf |
633ee86f0e3c6a24fb3672ea | 10.26434/chemrxiv-2022-7b6hv | Are the chemical families still there?
exploration of similarity among elements | The Periodic Table (PT) is perhaps the most famous and widespread icon of chemistry. It orders chemical elements
by their nuclear charge and groups them into families according to their similarity. Such arrangement was built using data about formulae of few compounds available in 19th century. Since then, the number of compounds has grown exponentially during the 20th and 21st centuries, and new types of compounds have been obtained that were unknown to pioneers, rising the question about the validity and generality of the PT. Can these patterns be extracted from current data or are they constrained to a particular chemical domain? To answer this question we conducted a Big Data exploration of chemical similarity using formulae of compounds reported since around 1800. We found that the similarities between elements of the same family are resilient to attacks and are ubiquitous along chemical contexts. We also found that PT groups approach true equivalence classes, being the most symmetrical and transitive on our data. These features point to
an underlying structure in the PT ruling the similarity between elements, which agrees with its fundamental nature. Time analysis revealed that since around 1980 all similarity relations are waning by an increasing production of unique formulae on almost all elements, leading to a singularization of elements. Nonetheless, PT families tend to be more frequently found, showing they prevail over any other similarity pattern. | Eugenio Llanos Ballestas; Wilmer Leal; Andrés Bernal; Jürgen Jost; Peter F. Stadler | Theoretical and Computational Chemistry; Theory - Computational; Chemoinformatics - Computational Chemistry | CC BY NC 4.0 | CHEMRXIV | 2022-10-07 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/633ee86f0e3c6a24fb3672ea/original/are-the-chemical-families-still-there-exploration-of-similarity-among-elements.pdf |
60c751de0f50db378e39786b | 10.26434/chemrxiv.12666773.v2 | Efficient C3-alkylsulfenylation of indoles under mild conditions using Lewis acid-activated 8-quinolinethiosulfonates. | The importance of sulfur-containing compounds in various fields, ranging from material
science1-2 to medicinal chemistry, 3
has called for the development of synthetic strategies to
form carbon-sulfur (C-S) bonds. Thus, numerous approaches based on the nucleophilicity of
thiols have been designed over the years, which mostly use air-sensitive noble metal catalysts.4-
9
At the opposite, the use of electrophilic sulfur reagents is also a powerful, more eco-friendly
approach, in particular for the sulfenylation of C-H bonds into C-S bonds.10-11 In this context,
the sulfenylation of indoles (Equation 1) has become a benchmark reaction to develop and test
new sulfenyl transfer reagents, because indoles are good nucleophiles and their occurrence in
many natural products or biological active compounds makes them attractive synthetic
targets.12-14 For instance, metal-catalyzed or metal-free protocols have been proposed, in
which disulfides, sulfinic acid and their salts, sulfonyl chlorides, sulfonylhydrazine, or Nthiophtalimides are used as source of electrophilic sulfur.10,15-16 Thiosulfonates (RSO2SR’) are
another class of emerging17 reagents, which were also studied for C-S bond formation18-20 and
for indole sulfenylation.21 However, despite the large pool of sulfenylation agents listed above,
the difficult activation of the chalcogen centre essentially limits these reagents to the formation
of C-S(aryl) bonds. On the other hand, the transfer of alkylsulfenyl groups requires harsher
activating conditions and is so far still limited<br /> | erwan galardon | Organic Synthesis and Reactions | CC BY NC ND 4.0 | CHEMRXIV | 2020-11-05 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/60c751de0f50db378e39786b/original/efficient-c3-alkylsulfenylation-of-indoles-under-mild-conditions-using-lewis-acid-activated-8-quinolinethiosulfonates.pdf |
659d25e49138d23161846c51 | 10.26434/chemrxiv-2024-262xc | Inherent directing group enabled, Co(III)-catalyzed C-H allylation/ vi-nylation of isoquinolones | The site-selective C8-allylation and vinylation of isoquinolones have been accomplished using allyl acetate and vinyl acetate and oxo group of isoquinolone as an inherent directing group in the presence of Co(III) catalysis. A plausible mechanism for the developed reaction has also been delineated based on preliminary mechanistic studies. Broad substrate scope with good to excellent yield and post-synthetic transformations of allyl and vinyl products feature the importance of reaction. | Sachin -; Tamanna Sharma; Devesh Chandra; Upendra Sharma | Organic Chemistry; Catalysis; Organometallic Chemistry; Organic Synthesis and Reactions; Homogeneous Catalysis; Bond Activation | CC BY NC ND 4.0 | CHEMRXIV | 2024-01-10 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/659d25e49138d23161846c51/original/inherent-directing-group-enabled-co-iii-catalyzed-c-h-allylation-vi-nylation-of-isoquinolones.pdf |
6111cde818911d671cdd54e9 | 10.26434/chemrxiv-2021-755dj | Direct Seawater Electrolysis via Synergistic Acidification by Inorganic Precipitation and Proton Flux from Bipolar Membrane | This report describes direct seawater electrolysis (DSE) wherein natural seawater is used as a catholyte without filtration or pretreatment; seawater is acidified to a pH of 2 while hydroxide ions are produced at the cathode by the hydrogen evolution reaction (HER). It results from the cooperative effect of hydroxide ions trapped through inorganic precipitation at the cathode and proton flux from water dissociation in a bipolar membrane (BPM; used as a separator). The acidification of the catholyte in the proposed BPM-DSE substantially mitigates cathode passivation, eliminates the requirement of additional processes for treatment of inorganic precipitates dispersed in the catholyte, and reduces the cathode potential (𝐸𝑐) required for the HER to enable long-term DSE. The BPM in this system plays a critical role in maintaining the electrolyte concentration, suppressing the chlorine evolution reaction (ClER), and maximizing the oxygen evolution reaction. These findings are expected to suggest a breakthrough toward large-scale operation of DSE that successfully overcomes challenges such as energy consumption, inorganic precipitation, ClER, and corrosion. | Ji-Hyung Han; Eunjin Jwa; Hongjun Lee; Eun Joong Kim; Joo-Youn Nam; Kyo Sik Hwang; Namjo Jeong; Jiyeon Choi; Hanki Kim; Youn-Cheul Jeung; Taek Dong Chung | Analytical Chemistry; Electrochemical Analysis | CC BY NC ND 4.0 | CHEMRXIV | 2021-08-10 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/6111cde818911d671cdd54e9/original/direct-seawater-electrolysis-via-synergistic-acidification-by-inorganic-precipitation-and-proton-flux-from-bipolar-membrane.pdf |
6705571ccec5d6c142990d64 | 10.26434/chemrxiv-2024-q8gtn | Upcycling orange waste biomass into bio-aerogels | The orange juice industry produces large amounts of by-products. In this work, we demonstrate for the first time a strategy to upcycle orange juice side streams into high-added-value materials, bio-aerogels. Bulk biomass and its fractions (peels, bagasse and pulp) were first subjected to citric acid hydrolysis, a “green” water-based treatment. Processing parameters (washing with water, biomass fraction, and biomass and citric acid concentrations) were tuned to maximize suspensions’ kinetic stability and produce homogenous aerogels. Removing soluble sugars during biomass washing and increasing biomass and citric acid contents led to higher stability of the suspensions, bearing mainly soluble pectin as a continuous phase with dispersed swollen insoluble fraction. Suspensions’ rheological properties, insoluble fraction contents, and swelling capacities were evaluated. The prepared suspensions were subjected to non-solvent-induced phase separation and solvent exchange with ethanol, followed by drying with supercritical carbon dioxide. The obtained bio-aerogels possessed low densities (< 0.1 g/cm³) and high specific surface areas (190 - 235 m²/g). The insoluble swollen fibers were porous and embedded in an open-pore nanostructured network. | Laís T. Possari; Caio G. Otoni; Tatiana Budtova; Sílvia H. P. Bettini | Materials Science; Polymer Science; Biological Materials; Biopolymers | CC BY NC 4.0 | CHEMRXIV | 2024-10-09 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/6705571ccec5d6c142990d64/original/upcycling-orange-waste-biomass-into-bio-aerogels.pdf |
63ca8c5af604d122315dcf0a | 10.26434/chemrxiv-2023-4dz2z | Nucleophile responsive charge-reversing polycations for pDNA transfection | Polycationic carriers promise low cost and scalable gene therapy treatments, however inefficient intracellular unpacking of the genetic cargo has limited transfection efficiency. Charge-reversing polycations, which transition from cationic to neutral or negative charge, can offer targeted intracellular DNA release. We describe a new class of charge-reversing polycation which undergoes a cationic-to-neutral conversion by a reaction with cellular nucleophiles. The deionization reaction is relatively slow with primary amines, and much faster with thiols. In mammalian cells, the intracellular environment has elevated concentrations of amino acids (~10x) and the thiol glutathione (~1000x). We propose this allows for decationization of the polymeric carrier slowly in the extracellular space and then rapidly in the intracellular milleu for DNA release. We demonstrate that in a lipopolyplex formulation this leads to both improved transfection and reduced cytotoxicity when compared to a non-responsive polycationic control. | Reece W. Lewis; Aswin Muralidharan; Benjamin Klemm; Pouyan E. Boukany; Rienk Eelkema | Biological and Medicinal Chemistry; Polymer Science; Nanoscience; Drug delivery systems; Polyelectrolytes - Polymers; Cell and Molecular Biology | CC BY NC 4.0 | CHEMRXIV | 2023-01-23 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/63ca8c5af604d122315dcf0a/original/nucleophile-responsive-charge-reversing-polycations-for-p-dna-transfection.pdf |
60c7401e469df46a69f42bc0 | 10.26434/chemrxiv.7609862.v1 | Evaluating Unexpectedly Short Non-covalent Distances in X-ray Crystal Structures of Proteins with Electronic Structure Analysis | <div><div><div><p>We investigate unexpectedly short non-covalent distances (< 85% of the sum of van der Waals radii) in atomically resolved X-ray crystal structures of proteins. We curate over 13,000 high quality protein crystal structures and an ultra-high resolution (1.2 Å or better) subset containing > 1,000 structures. Although our non-covalent distance criterion excludes standard hydrogen bonds known to be essential in protein stability, we observe over 82,000 close contacts in the curated protein structures. Analysis of the frequency of amino acids participating in these interactions demonstrates some expected trends (i.e., enrichment of charged Lys, Arg, Asp, and Glu) but also reveals unexpected enhancement of Tyr in such interactions. Nearly all amino acids are observed to form at least one close contact with all other amino acids, and most interactions are preserved in the much smaller ultra high-resolution subset. We quantum-mechanically characterize the interaction energetics of a subset of > 6,000 close contacts with symmetry adapted perturbation theory to enable decomposition of interactions. We observe the majority of close contacts to be favorable. The shortest favorable non-covalent distances are under 2.2 Å and are very repulsive when characterized with classical force fields. This analysis reveals stabilization by a combination of electrostatic and charge transfer effects between hydrophobic (i.e., Val, Ile, Leu) amino acids and charged Asp or Glu. We also observe a unique hydrogen bonding configuration between Tyr and Asn/Gln involving both residues acting simultaneously as hydrogen bond donors and acceptors. This work confirms the importance of first-principles simulation in explaining unexpected geometries in protein crystal structures.</p></div></div></div> | Helena W. Qi; Heather Kulik | Bonding; Computational Chemistry and Modeling | CC BY NC ND 4.0 | CHEMRXIV | 2019-01-21 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/60c7401e469df46a69f42bc0/original/evaluating-unexpectedly-short-non-covalent-distances-in-x-ray-crystal-structures-of-proteins-with-electronic-structure-analysis.pdf |
66ef4a4ecec5d6c142ca906b | 10.26434/chemrxiv-2024-r26gn | A novel flame-retardant lithium fluoroborate salt for LNMO-graphite-based Li-ion batteries | A novel lithium salt (lithium bis-fluoro bis-nonafluoro-tert-butoxy borate) shows high solubility (>1 M) and flame-retardant properties in an electrolyte solution with conventional carbonate solvents as well as stable cycling in a high-voltage (4.8 V) LiNi0.5Mn1.5O4-graphite based lithium-ion battery. | Binayak Roy; Urbi Pal; Patrick Howlett; Douglas Macfarlane | Energy; Energy Storage | CC BY NC ND 4.0 | CHEMRXIV | 2024-09-25 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/66ef4a4ecec5d6c142ca906b/original/a-novel-flame-retardant-lithium-fluoroborate-salt-for-lnmo-graphite-based-li-ion-batteries.pdf |
65cf21119138d231613facc8 | 10.26434/chemrxiv-2024-833fs | Automated synthesis of fucoidan enables molecular investigations in marine glycobiology | Fucoidan, a sulfated polysaccharide found in algae, occupies a central yet enigmatic role in marine carbon sequestration and exhibits a wide array of bioactivities. However, the inherent molecular diversity and structural complexity of fucoidan hinders precise structure-function studies. To address this, we present a rapid and reproducible automated synthesis method for generating well-defined linear and branched α-fucan oligosaccharides. Our syntheses include oligosaccharides with up to 20 cis-glycosidic linkages, diverse branching patterns, and 11 sulfate monoesters. In this study, we showcase the utility of these glycans by (i) characterizing two endo-acting fucoidan glycoside hydrolases (GH107), (ii) serving as standards for NMR experiments to confirm suggested structures of algal fucoidans, and (iii) developing a fucoidan microarray. This microarray enabled precise screening of the molecular specificity of four monoclonal antibodies targeting fucoidan. Utilizing the antibody BAM2, identified here for its specificity to α-(1→3)-fucoidans featuring 4-O-sulfate esters, we provide evidence that such a fucoidan motif is present in a globally abundant marine diatom, Thalassiosira weissflogii. Automated glycan assembly provides a robust platform for accelerating research in marine glycobiology, offering access to fucoidan oligosaccharides with distinct structures, thereby facilitating advancements in our collective understanding of how fucoidan's structure influences its function. | Conor Crawford; Mikkel Schultz-Johansen; Phuong Luong; Silvia Vidal-Melgosa; Jan-Hendrik Hehemann; Peter Seeberger | Biological and Medicinal Chemistry; Organic Chemistry; Biochemistry; Chemical Biology | CC BY NC ND 4.0 | CHEMRXIV | 2024-02-19 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/65cf21119138d231613facc8/original/automated-synthesis-of-fucoidan-enables-molecular-investigations-in-marine-glycobiology.pdf |
60c74747bb8c1ade763daa05 | 10.26434/chemrxiv.11606019.v1 | Cheminformatics Modeling of Closantel Analogues for Treating River Blindness | <p></p><p>Onchocerciasis (also known as river
blindness<i>)</i> is a neglected tropical
disease caused by the <i>Onchocerca volvulus</i>
parasitic nematode. Currently, the only approved drug for treating this disease
is ivermectin, which is a broad-spectrum antiparasitic agent. However, signs of
resistance towards ivermectin have started to emerge. New therapeutic agents
are thus urgently needed. The OvCHT1 chitinase enzyme from <i>O. volvulus</i> has been established as a relevant biological target
for combatting river blindness. The veterinary anthelmintic drug closantel has
been found to be a potent, micro-molar OvCHT1 inhibitor. Herein, we
investigated the chemical space of closantel and all its synthesized analogues,
focusing on the analysis of their potential binding modes towards OvCHT1. First,
we conducted an unsupervised hierarchical clustering to group highly similar
analogues and explore structure-activity relationships. Second, we conducted a
structure-based molecular docking to predict and study the binding modes of all
57 closantel analogues in the active site of OvCHT1. Third, we screened more
than 4 million lead-like compounds from the ZINC library to identify other structurally
similar ligands that could potentially bind to OvCHT1. The cheminformatics analysis of the closantel analogues illustrated
how minor structural changes in closantel analogues can impact their OvCHT1
activity.</p><p></p> | Melaine A. Kuenemann; Phyo Phyo Zin; Sravya Kuchibhotla; Denis Fourches | Computational Chemistry and Modeling; Chemoinformatics - Computational Chemistry | CC BY NC ND 4.0 | CHEMRXIV | 2020-01-17 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/60c74747bb8c1ade763daa05/original/cheminformatics-modeling-of-closantel-analogues-for-treating-river-blindness.pdf |
60c754df0f50db168b397dd9 | 10.26434/chemrxiv.13804841.v1 | CO2-Involved and Isocyanide-based Three-component Polymerization toward Functional Heterocyclic Polymers with Self-assembly and Sensing Properties | CO<sub>2</sub> utilization
has been a hot research topic in academic
and industrial respects.
Besides converting CO<sub>2</sub> into chemicals and fuels, incorporating it into
the polymers to construct functional materials is another promising strategy.
However, the CO<sub>2</sub>-involved polymerization techniques should be
further developed. In this work, a facile and efficient CO<sub>2</sub>-involved
multicomponent polymerization is successfully developed. The reaction of monomers
of CO<sub>2</sub>, isocyanides and 2-iodoanilines readily produces soluble and
thermally stable <a>poly(</a><a>benzoyleneurea</a>)s
with well-defined structures under mild conditions. Thanks to the formed amide
groups in the heterocyclic units in the main-chains, the resultant polymers <a>could self-assemble into </a>spheres with sizes between 200
and 1000 nm. <a>The
polymers containing tetraphenylethylene (TPE) unit show the unique aggregation-enhanced
emission (AEE) features, which could be used to visualize the self-assembly process
and morphologies under UV irradiation</a><a>, and serve as fluorescence probe to selectively and
sensitively detect Au<sup>3+</sup> ions. </a>Notably,
the polymers<i> </i>containing<i> cis</i>- and <i>trans</i>-TPE units exhibit different behaviors in self-assembly and
limit of detection for <a>Au<sup>3+</sup> ions</a> due to
the different intermolecular interactions. Thus, this work not only provides a
new strategy for CO<sub>2</sub> utilization but also furnishes
a series of functional heterocyclic polymers for diverse applications. | Dongming Liu; Bo Song; JIa Wang; Baoxi Li; Bingnan Wang; Mingzhao Li; Anjun Qin; Ben Zhong Tang | Polymer morphology | CC BY NC ND 4.0 | CHEMRXIV | 2021-02-10 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/60c754df0f50db168b397dd9/original/co2-involved-and-isocyanide-based-three-component-polymerization-toward-functional-heterocyclic-polymers-with-self-assembly-and-sensing-properties.pdf |
619a9d5064a70767707aa768 | 10.26434/chemrxiv-2021-g0dc2 | Elucidating the Mechanism of Excited State Bond Homolysis in Nickel–Bipyridine Photoredox Catalysts | Ni 2,2’–bipyridine (bpy) complexes are commonly employed photoredox catalysts of bond-forming reactions in organic chemistry. However, the mechanisms by which they operate are still under investigation. One potential mode of catalysis is via entry into Ni(I)/Ni(III) cycles, which can be made possible by light-induced, excited state Ni(II)–C bond homolysis. Here we report experimental and computational analyses of a library of Ni(II)-bpy aryl halide complexes, Ni(Rbpy)(R′Ph)Cl (R = MeO, t-Bu, H, MeOOC; R′ = CH3, H, OMe, F, CF3), to illuminate the mechanism of excited state bond homolysis. At given excitation wavelengths, photochemical homolysis rates span two orders of magnitude across these structures and correlate linearly with Hammett parameters of both bpy and aryl ligands, reflecting structural control over key metal-to-ligand charge transfer (MLCT) and ligand-to-metal charge transfer (LMCT) excited state potential energy surfaces (PESs). Temperature- and wavelength-dependent investigations reveal moderate excited state barriers (ΔH‡ ~4 kcal mol-1) and a minimum energy excitation threshold (~55 kcal mol-1, 525 nm), respectively. Correlations to electronic structure calculations further support a mechanism in which repulsive triplet excited state PESs featuring a critical aryl-to-Ni LMCT lead to bond rupture. Structural control over excited state PESs provides a rational approach to utilize photonic energy and leverage excited state bond homolysis processes in synthetic chemistry. | David Cagan; Daniel Bím; Breno Silva; Nathanael Kazmierczak; Brendon McNicholas; Ryan Hadt | Theoretical and Computational Chemistry; Physical Chemistry; Organometallic Chemistry; Computational Chemistry and Modeling; Spectroscopy (Organomet.); Photochemistry (Physical Chem.) | CC BY NC ND 4.0 | CHEMRXIV | 2021-11-22 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/619a9d5064a70767707aa768/original/elucidating-the-mechanism-of-excited-state-bond-homolysis-in-nickel-bipyridine-photoredox-catalysts.pdf |
60c754e9469df47c3ff45033 | 10.26434/chemrxiv.12999524.v4 | Extension of the CL&Pol Polarizable Force Field to Electrolytes, Protic Ionic Liquids and Deep Eutectic Solvents | The polarizable CL&Pol force field presented in our previous study, Transferable, Polarizable Force Field for Ionic Liquids (J. Chem. Theory Comput. 2019, 15, 5858, DOI: 10.1021/acs.jctc.9b00689), is extended to electrolytes, protic ionic liquids, deep eutectic solvents, and glycols. These systems are problematic in polarizable simulations because they contain either small, highly charged ions or strong hydrogen bonds, which cause trajectory instabilities due to the pull exerted on the induced dipoles. We use a Tang-Toennies function to dampen, or smear, the interactions between charges and induced dipole at short range involving small, highly charged atoms (such as hydrogen or lithium), thus preventing the ``polarization catastrophe''. The new force field gives stable trajectories and is validated through comparison with experimental data on density, viscosity, and ion diffusion coefficients of liquid systems of the above-mentioned classes. The results also shed light on the hydrogen-bonding pattern in ethylammonium nitrate, a protic ionic liquid, for which the literature contains conflicting views. We describe the implementation of the Tang-Toennies damping function, of the temperature-grouped Nosé-Hoover thermostat for polarizable molecular dynamics and of the periodic perturbation method for viscosity evaluation from non-equilibrium trajectories in the LAMMPS molecular dynamics code. The main result of this work is the wider applicability of the CL&Pol polarizable force field to new, important classes of fluids, achieving robust trajectories and a good description of equilibrium and transport properties in challenging systems. The fragment-based approach of CL&Pol will allow ready extension to a wide variety of protic ionic liquids, deep eutectic solvents and electrolytes.<br /> | Agilio Padua; Kateryna Goloviznina; Margarida Costa Gomes; Zheng Gong | Computational Chemistry and Modeling | CC BY NC ND 4.0 | CHEMRXIV | 2021-01-22 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/60c754e9469df47c3ff45033/original/extension-of-the-cl-pol-polarizable-force-field-to-electrolytes-protic-ionic-liquids-and-deep-eutectic-solvents.pdf |
677be69b6dde43c9087f1d4a | 10.26434/chemrxiv-2025-68mnk | A systematic approach to parameterization of disaccharides for the Martini 3 coarse-grained force-field | Sugars are ubiquitous in biology; they occur in all kingdoms of life. Despite their prevalence they have often been somewhat neglected in studies of structure-dynamics-function relationships of macromolecules to which they are attached, with the exception of nucleic acids. This is largely due to inherent difficulties of studying not only conformational dynamics of sugars using experimental methods, but indeed also resolving their static structures. Molecular Dynamics (MD) simulations offer a route to prediction of conformational ensembles and the time-dependent behaviour of sugars and glycosylated macromolecules. However, at the all-atom level of detail, MD simulations are often too computationally demanding to allow a systematic investigation of molecular interactions in systems of interest. To overcome this, large scale simulations of complex biological systems have profited from advancements in coarse-grained (CG) simulations. Perhaps the most widely used CG force field for biomolecular simulations is Martini. Here we present a parameter set for glucose and mannose-based disaccharides for Martini3. The generation of the CG parameters from atomistic trajectories is automated as fully as possible and where not possible, we provide details of the protocol used for manual intervention. | Astrid F. Brandner; Iain P. S. Smith; Siewert J. Marrink; Paulo C. T. Souza; Syma Khalid | Theoretical and Computational Chemistry; Biological and Medicinal Chemistry; Biophysics; Computational Chemistry and Modeling | CC BY 4.0 | CHEMRXIV | 2025-01-08 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/677be69b6dde43c9087f1d4a/original/a-systematic-approach-to-parameterization-of-disaccharides-for-the-martini-3-coarse-grained-force-field.pdf |
648ffd56be16ad5c5725182a | 10.26434/chemrxiv-2023-s509z-v2 | Morphological plasticity of LiCl clusters interacting with Grignard reagent in tetrahydrofuran | Ab initio molecular dynamics simulations are used to explore tetrahydrofuran (THF) solutions containing pure LiCl, and LiCl with CH3MgCl, as model constituents of the turbo Grignard reagent. LiCl aggregates as Li4Cl4, which preferentially assumes compact cubane-like conformations. In particular, an open-edge pseudo tetrahedral frame is promoted by solvent-assisted Li-Cl bond cleavage. Among the Grignard species involved in the Schlenk equilibrium, LiCl prefers coordinating MgCl2 through m-Cl bridges. Using a 1:1 Li:Mg ratio, the plastic tetranuclear LiCl cluster decomposes to a highly solvated mixed LiCl·MgCl2 aggregate with prevalent Li-(m2-Cl)2-Mg rings and linear LiCl entities. The MgCl2-assisted disaggregation of Li4Cl4 occurs through transient structures analogous to those detected for pure LiCl in THF, also corresponding to moieties observed in the solid state. This study identifies a synergistic role of LiCl for the determination of the compounds present in turbo Grignard solutions, in a scenario where LiCl shifts the Schlenk equilibrium promoting a higher concentration of dialkylmagnesium, meanwhile decomposing into smaller, more soluble, mixed Li:Mg:Cl clusters. | Marinella de Giovanetti; Sondre Hilmar Hopen Eliasson; Abril Carolina Castro; Odile Eisenstein; Michele Cascella | Theoretical and Computational Chemistry; Organometallic Chemistry; Computational Chemistry and Modeling; Main Group Chemistry (Organomet.) | CC BY 4.0 | CHEMRXIV | 2023-06-19 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/648ffd56be16ad5c5725182a/original/morphological-plasticity-of-li-cl-clusters-interacting-with-grignard-reagent-in-tetrahydrofuran.pdf |
65410dc248dad23120c6e954 | 10.26434/chemrxiv-2023-tdl2v | Graph to Activation Energy Models Easily Reach Irreducible Errors but Show Limited Transferability | Activation energy characterization of competing reactions is a costly, but crucial step for understanding the kinetic relevance of distinct reaction pathways, product yields, and myriad other properties of reacting systems. The standard methodology for activation energy characterization has historically been a transition state search using the highest level of theory that can be afforded. However recently, several groups have popularized the idea of predicting activation energies directly, based on nothing more than the reactant and product graphs, a sufficiently complex neural network, and a broad enough dataset. Here, we have revisited this task using the recently developed Reaction Graph Depth 1 (RGD1) transition state dataset and several newly developed graph attention architectures. All of these new architectures achieve similar state-of-the-art results of ~4 kcal/mol mean absolute error on withheld testing sets of reactions but poor performance on external testing sets composed of reactions with differing mechanisms, reaction molecularity, or reactant size distribution. Limited transferability is also shown to be shared by other contemporary graph to activation energy architectures through a series of case-studies. We conclude that an array of standard graph architectures can already achieve results comparable to the irreducible error of available reaction datasets but that out-of-distribution performance remains poor. | Sai Mahit Vadaddi; Qiyuan Zhao; Brett M Savoie | Theoretical and Computational Chemistry; Physical Chemistry; Machine Learning; Artificial Intelligence; Chemoinformatics - Computational Chemistry | CC BY 4.0 | CHEMRXIV | 2023-11-01 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/65410dc248dad23120c6e954/original/graph-to-activation-energy-models-easily-reach-irreducible-errors-but-show-limited-transferability.pdf |
60c743b8bdbb893906a386c8 | 10.26434/chemrxiv.9630695.v1 | Renewable Diesel Blendstocks and Biopriviliged Chemicals Distilled from Algal Biocrude Oil Converted via Hydrothermal Liquefaction | This study aims to produce renewable diesel and
biopriviliged chemicals from microalgae that can thrive in wastewater
environment. <i>Spirulina</i> (SP) was
converted into biocrude oil at 300ºC for a 30-minute reaction time via hydrothermal
liquefaction (HTL). Next, fractional distillation was used to
separate SP-derived biocrude oil into different distillates. It was found that 62%
of the viscous SP-derived biocrude oil can be separated into liquids at about 270ºC
(steam temperature of the distillation). Physicochemical characterizations, including
density, viscosity, acidity, elemental compositions, higher heating values and chemical
compositions, were carried out with the distillates separated from SP-derived
biocrude oil. These analyses showed that 15% distillates could be used as
renewable diesel because they have similar heating values (43-46 MJ/kg) and
carbon numbers (ranging from C8 to C18) to petroleum diesel. The Van Krevelan
diagram of the distillates suggests that deoxygenation was effectively achieved
by fractional distillation. In addition, GC-MS analysis indicates that some
distillates contain biopriviliged chemicals like aromatics, phenols and fatty
nitriles that can be used as commodity chemicals. An algal biorefinery roadmap
was proposed based on the analyses of different distillates from the SP-derived
biocrude oil. Finally, the fuel specification analysis was conducted with the
drop-in renewable diesel, which was prepared with 10 vol.% (HTL10) distillates
and 90 vol.% petroleum diesel. According to the fuel specification analysis,
HTL10 exhibited a qualified lubricity (<520 µm), acidity (<0.3 mg KOH/g)
and oxidation stability (>6 hr), as well as a comparable net heat of
combustion (1% lower), ash content (29% lower) and viscosity (17% lower) to
those of petroleum diesel. Ultimately, it is expected that this study can provide
insights for potential application of algal biocrude oil converted via HTL. | Wan-Ting (Grace) Chen; Zhenwei Wu; Buchun Si; Yuanhui Zhang | Fuels - Energy Science | CC BY NC ND 4.0 | CHEMRXIV | 2019-08-15 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/60c743b8bdbb893906a386c8/original/renewable-diesel-blendstocks-and-biopriviliged-chemicals-distilled-from-algal-biocrude-oil-converted-via-hydrothermal-liquefaction.pdf |
65d76926e9ebbb4db9f6a4ca | 10.26434/chemrxiv-2024-4kmw8 | Azophosphines: Synthesis, Structure and Coordination Chemistry | The conceptual replacement of nitrogen with phosphorus in common organic functional groups unlocks new properties and reactivity. The phosphorus-containing analogues of triazenes are underexplored but offer great potential as flexible and small bite-angle ligands. This manuscript explores the synthesis and characterisation of a family of air-stable azophosphine-borane complexes, and their subsequent deprotection to the free azophosphines. These compounds are structurally characterised, both experimentally and computationally, and highlight the availability of the phosphorus lone pair for coordination. This is confirmed by demonstrating that neutral azophosphines can act as ligands in Ru complexes, and can coordinate as monodentate or bidentate ligands in a controlled manner, in contrast to their nitrogen analogues. | Emma Jordan; Ethan Calder; Holly Adcock; Louise Male; Martin Nieger; Chris Slootweg; Andrew Jupp | Inorganic Chemistry; Coordination Chemistry (Inorg.); Main Group Chemistry (Inorg.) | CC BY 4.0 | CHEMRXIV | 2024-02-23 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/65d76926e9ebbb4db9f6a4ca/original/azophosphines-synthesis-structure-and-coordination-chemistry.pdf |
649ef666ba3e99daef4ccc18 | 10.26434/chemrxiv-2023-lchmv | De Novo Catalyst Discovery: Fast Identification of New Catalyst Candidates | Very recently our group has demonstrated how a genetic algorithm (GA) starting from random tertiary amines can be used to discover a new and efficient catalyst for the alcohol-mediated Morita- Baylis-Hillman (MBH) reaction. In particular, the discovered catalyst was shown experimentally to be eight times more active than 1,4-diazabicyclo[2.2.2]octane (DABCO), which is commonly used to catalyze the MBH reaction. This represents a breakthrough in using generative models for catalyst optimization. However, the GA-procedure, and hence discovery, relied on two important pieces of information; 1) the knowledge that tertiary amines catalyze the reaction and 2) the mechanism and reaction profile for the catalyzed reaction, in particular the transition state structure of the rate determining step. Thus truly de novo catalyst discovery must also include these steps. Here we present such a method for discovering catalyst candidates for a specific reaction while simultaneously proposing a mechanism for the catalyzed reaction. We use the method to show that tertiary amines and phosphines are potential catalysts for the MBH reaction by screening a selection of 11 molecular templates representing common functional groups. The presented method relies on an automated reaction discovery workflow using meta-dynamics calculations. Combining this method for catalyst candidate discovery with our GA-based catalyst optimization method results in an algorithm for truly de novo catalyst discovery | Maria Harris Rasmussen; Julius Seumer; Jan Halborg Jensen | Catalysis; Homogeneous Catalysis; Organocatalysis | CC BY 4.0 | CHEMRXIV | 2023-07-03 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/649ef666ba3e99daef4ccc18/original/de-novo-catalyst-discovery-fast-identification-of-new-catalyst-candidates.pdf |
65308f8cc3693ca9936e02a6 | 10.26434/chemrxiv-2023-r73tm | Electrocatalytic Urea Synthesis via N2 Dimerization and
Universal Descriptor | Electrocatalytic urea synthesis through N2 + CO2 co-reduction and C−N coupling is a
promising and sustainable alternative to harsh industrial processes. Despite considerable efforts, limited
progress has been made due to the challenges of breaking inert N≡N bonds for C−N coupling,
competing side reactions, and the absence of theoretical principles guiding catalyst design. In this study,
we propose a new mechanism for highly electrocatalytic urea synthesis using two adsorbed N2
molecules and CO as nitrogen and carbon sources, respectively. This mechanism circumvents the
challenging step of N≡N bond breaking and selective CO2 to CO reduction, as the free CO molecule
inserts into dimerized *N2 and binds concurrently with two N atoms, forming a unique urea precursor
*NNCONN* with both thermodynamic and kinetic feasibility. Through the new mechanism, Ti2@C4N3
and V2@C4N3 are identified as highly active catalysts for electrocatalytic urea formation, exhibiting
low onset potentials of -0.741 and -0.738 V, respectively. Importantly, taking transition metal atoms
anchored on porous graphite-like carbonitride (TM2@C4N3) as prototypes, we introduce a simple
descriptor, namely, effective d electron number (Φ), to quantitatively describe the structure-activity
relationships for urea formation. This descriptor incorporates inherent atomic properties of the catalyst,
such as the number of d electrons, electronegativity of the metal atoms, and generalized
electronegativity of the substrate atoms, making it potentially applicable to other urea catalysts. Our
work advances novel mechanisms and provides a universal guiding principle for catalyst design in urea
electrochemical synthesis. | Junxian Liu; Xingshuai Lv; Yandong Ma; Sean Smith; Yuantong Gu; Liangzhi Kou | Theoretical and Computational Chemistry; Materials Science; Catalysis | CC BY NC ND 4.0 | CHEMRXIV | 2023-10-19 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/65308f8cc3693ca9936e02a6/original/electrocatalytic-urea-synthesis-via-n2-dimerization-and-universal-descriptor.pdf |
6616b61491aefa6ce14444fe | 10.26434/chemrxiv-2024-8gdk1 | Application of confocal laser scanning microscopy to investigation of micro crystals in transparent amorphous media: photoluminescence tomography and spectroscopy of CdZnSSe crystallites in historical silicate glass | Recently, photoluminescence tomography based on the confocal laser scanning microscopy with two-photon excitation has been developed to study the distribution of point and extended defects in the bulk of ZnSe laser crystals. This article presents the use of the tomography to investigate luminescent micro inclusions in transparent amorphous media such as silicate glass. Studies of CdZnSSe crystals synthesized in a silicate glass melt have been carried out using the tomography with both two-photon and single-photon excitation of luminescence. Zn-rich glass manufactured in the 19th century has been found to contain micron-sized crystals of CdZnSSe of hexagonal crystal system exhibiting intense photoluminescence. The photoluminescence band of these crystals has been found to peak at about 2.1 eV (∼ 590 nm) at 300 K. Minor shifts in the maximum of bands and changes in their shape in individual crystals or at tomogram points within the crystal are associated with variations in their composition. Changes in the photoluminescence band shape and maximum due to the excitation of luminescence in CdZnSSe crystallites by laser radiation of different energies have also been observed in this study. | Vladimir A. Yuryev; Oleg V. Uvarov; Tatyana V. Yuryeva; Victor P. Kalinushkin | Materials Science; Dyes and Chromophores | CC BY NC ND 4.0 | CHEMRXIV | 2024-04-12 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/6616b61491aefa6ce14444fe/original/application-of-confocal-laser-scanning-microscopy-to-investigation-of-micro-crystals-in-transparent-amorphous-media-photoluminescence-tomography-and-spectroscopy-of-cd-zn-s-se-crystallites-in-historical-silicate-glass.pdf |
67cda0bd6dde43c9082777e2 | 10.26434/chemrxiv-2025-lqllp | Unlocking a Ferrocenium Superoxidizer with the Perfluorinated Cp* Ligand | The photolytically induced arene displacement of [Fe(C5H5)(oDCB)][PF6] (oDCB = ortho-dichlorobenzene) in the presence of [NEt4][C5(CF3)5] afforded the highly fluorinated and benchstable ferrocene [Fe(C5H5)(C5(CF3)5)]. The perfluorinated Cp* ligand exerts an extreme electron withdrawing effect on the ferrocene with an Epa of up to 1.70 V (vs. Fc/Fc+). This proved to be the highest value obtained for any ferrocene reported so far. The corresponding stable and storable ferrocenium complex [Fe(C5H5)(C5(CF3)5)][AsF6] was generated in quantitative yield and represents not only the most oxidizing ferrocenium species, but also the strongest known isolable organometallic oxidizer. Its strength was demonstrated by the twofold oxidation of [Fe(C5(CH3)5)2] to its dication and an oxidative C-H activation of ortho-terphenyl. This unprecedented redox chemistry combined with perfluorocarbon solubility allows for selective and quantitative recycling of the highly fluorinated ferrocene. Together with the low basicity and inertness of [Fe(C5H5)(C5(CF3)5)], the chemistry of strong oxidizers is herein expanded into organometallics. | Robin Sievers; Nico G. Kub; Tim-Niclas Streit; Marc Reimann; Günther Thiele; Martin Kaupp; Moritz Malischewski | Organic Chemistry; Inorganic Chemistry; Organometallic Chemistry; Organometallic Compounds; Electrochemistry - Organometallic; Transition Metal Complexes (Organomet.) | CC BY NC ND 4.0 | CHEMRXIV | 2025-03-12 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/67cda0bd6dde43c9082777e2/original/unlocking-a-ferrocenium-superoxidizer-with-the-perfluorinated-cp-ligand.pdf |
60c74167bb8c1a65e63d9f3b | 10.26434/chemrxiv.8044796.v1 | Understanding the mechanism of enhanced cycling stability in Sn-Sb composite Na-ion battery anodes: in-operando alloying and diffusion barriers | Sn-Sb composites are of great interest for high capacity sodium ion batteries due to their high stability, but because multiple phases and alloyed compositions are formed during cycling, the roles of each are challenging to deduce. In this work, two approaches were taken to investigate the importance of β-SnSb formation on the cycling stability of Sn-rich Sn-Sb composite sodium-ion battery (SIB) anodes. First, to tease out the role of each component, thin layers of amorphous silicon with thicknesses ranging from 0.5 to 10 nm, were incorporated between Sn and Sb layers, of equal thicknesses. Silicon has low solubility in both tin and antimony, and thus acts as a barrier layer that can interfere with the formation of Sn-Sb alloys. The equivalent composition of this sandwich structure was Sn<sub>53</sub>Sb<sub>47</sub>. Upon electrochemical cycling, a clear correlation between capacity retention and Si thickness was observed, and it was found that a 1 nm thick Si layer was sufficient to inhibit the formation of the β-SnSb intermetallic, resulting in loss of the capacity of the tin layer after a few tens of cycles. The second approach involved capping a Sn film with increasingly thicker Sb layers. Thicker antimony layers were found to have a large positive influence on cycling stability with a marked drop-off in the capacity retention when there is not enough Sb to fully convert the bilayer into β-SnSb. These results point to the necessity of the Sn and Sb being in intimate contact prior to cycling for the β-SnSb phase to form in-operando, which is necessary for the excellent capacity retention of the Sn-Sb system. | W. Peter Kalisvaart; Hezhen Xie; Brian Olsen; Erik Luber; Jillian Buriak | Energy Storage | CC BY NC ND 4.0 | CHEMRXIV | 2019-04-29 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/60c74167bb8c1a65e63d9f3b/original/understanding-the-mechanism-of-enhanced-cycling-stability-in-sn-sb-composite-na-ion-battery-anodes-in-operando-alloying-and-diffusion-barriers.pdf |
60e693f88a469bc09478548e | 10.26434/chemrxiv-2021-gxw1n | Nonadiabatic dynamics with spin-flip versus linear-response time-dependent density functional theory: A case study for the protonated Schiff base C5H6NH2+ | Nonadiabatic trajectory surface hopping simulations are reported for trans-C5H6NH2+, a model of the rhodopsin chromophore, using the augmented fewest-switches algorithm. Electronic structure calculations were performed using time-dependent density functional theory (TDDFT) in both its conventional linear-response (LR) and its spin-flip (SF) formulations. In the SF-TDDFT case, spin contamination in the low-lying singlet states is removed by projecting out the lowest triplet component during iterative solution of the TDDFT eigenvalue problem. The results show that SF-TDDFT is able to correctly describe the photoisomerization of trans-C5H6NH2+, with favorable comparison to previous studies using multireference electronic structure methods. In contrast, conventional LR-TDDFT affords qualitatively different photodynamics due to an incorrect excited-state potential surface near the Franck-Condon region. In addition, the photochemistry (involving
pre-twisting of the central double bond) appears to be different for SF- and LR-TDDFT, which may be a consequence of different conical intersection topographies afforded by these two methods. The present results contrast with previous surface-hopping studies suggesting that the LR-TDDFT method's incorrect topology around S1/S0 conical intersections is immaterial to the photodynamics. | Xing Zhang; John Herbert | Theoretical and Computational Chemistry; Physical Chemistry; Computational Chemistry and Modeling; Photochemistry (Physical Chem.); Quantum Mechanics | CC BY 4.0 | CHEMRXIV | 2021-07-08 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/60e693f88a469bc09478548e/original/nonadiabatic-dynamics-with-spin-flip-versus-linear-response-time-dependent-density-functional-theory-a-case-study-for-the-protonated-schiff-base-c5h6nh2.pdf |
60c74b58702a9bae4218b408 | 10.26434/chemrxiv.12320855.v1 | Atomic Layer Deposition of CeOx Nanoclusters on TiO2 | Titanium dioxide has a band-gap in the ultra violet region and there
have been many efforts to shift light absorption to the visible region. In this
regard, surface modification with metal oxide clusters has been used to promote
band-gap reduction. CeO<sub>x</sub>-modified<sub> </sub>TiO<sub>2</sub> materials
have exhibited enhanced catalytic activity in water gas shift, but the
deposition process used is not well-understood or suitable for powder materials.
Atomic layer deposition (ALD) has been used for deposition of cerium oxide on
TiO<sub>2</sub>. The experimentally reported growth rates using typical Ce
metal precursors such as β-diketonates and cyclopentadienyls are low, with reported growth rates
of <i>ca. </i>0.2-0.4 Å/cycle. In this
paper, we have performed density functional theory calculations to reveal the reaction
mechanism of the metal precursor pulse together with experimental studies of ALD
of CeO<sub>x</sub> using two Ce precursors, Ce(TMHD)<sub>4</sub> and Ce(MeCp)<sub>3</sub>.
The nature and stability of hydroxyl groups on anatase and rutile TiO<sub>2</sub>
surfaces are determined and used as starting substrates. Adsorption of the
cerium precursors on the hydroxylated TiO<sub>2</sub> surfaces reduces the coverage
of surface hydroxyls. Computed activation barriers for ligand elimination in
Ce(MeCp)<sub>3</sub> indicate that ligand elimination is not possible on
anatase (101) and rutile (100) surface, but it is possible on anatase (001) and
rutile (110). The ligand elimination in Ce(TMHD)<sub>4</sub> is via breaking the
Ce-O bond and hydrogen transfer from hydroxyl groups. For this precursor, the ligand elimination on the majority surface
facets of anatase and rutile TiO<sub>2</sub> are endothermic and not favourable.
It is difficult to deposit Ce atom onto hydroxylated TiO<sub>2</sub> surface
using Ce(TMHD)<sub>4</sub> as precursor. Attempts for deposit cerium oxide on TiO<sub>2 </sub>nanoparticles
that expose the anatase (101) surface show at best a low deposition rate and
this can be explained by the non-favorable ligand elimination reactions at this
surface. | Ji Liu; Saeed Saedy; Rakshita Verma; J. Ruud van Ommen; Michael Nolan | Catalysts; Coating Materials; Materials Processing; Thin Films; Computational Chemistry and Modeling; Theory - Computational; Physical and Chemical Processes; Surface | CC BY NC ND 4.0 | CHEMRXIV | 2020-05-19 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/60c74b58702a9bae4218b408/original/atomic-layer-deposition-of-ce-ox-nanoclusters-on-ti-o2.pdf |
61544003093c9a84086cd75c | 10.26434/chemrxiv-2021-6z3b3 | Simulation of Defects, Flexibility and Rupture in Biopolymer Networks | Networks of biopolymers occur often in nature, and are vulnerable to damage over time.
In this work, a coarse grained model of collagen IV molecules is applied in a 2D hexagonal network and
the mechanisms by which these networks can rupture are explored.
The networks are stretched linearly in order to study their structural limits and mechanism of rupture over
timescale of up to 100 microseconds.
Metrics are developed to track the damage networks suffer over time, and qualitatively analyse ruptures that occur.
Further simulations repeatedly stretch the networks sinusoidally to mimic the in vivo strains.
Defects of increasing levels of complexity are introduced into an ordered network, and
their effect on the rupturing behaviour of the biopolymer networks studied.
The effect of introducing holes of varying size in the network, as well as strips of finite
width to mimic surgical damage are studied. These demonstrate the importance of the flexibility
of the networks to preventing damage. | Matthew H. J. Bailey; Mark Wilson | Theoretical and Computational Chemistry; Computational Chemistry and Modeling | CC BY 4.0 | CHEMRXIV | 2021-09-29 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/61544003093c9a84086cd75c/original/simulation-of-defects-flexibility-and-rupture-in-biopolymer-networks.pdf |
6669df63409abc03454349aa | 10.26434/chemrxiv-2024-383j5 | metallicious: Automated force-field parametrization of covalently bound metals for supramolecular structures | Metal ions play a central functional and structural role in many molecular structures, from small catalysts to metal-organic frameworks (MOFs) and proteins. Computational studies of these systems typically employ classical or quantum mechanical approaches or a combination of both. Among classical models, only the covalent metal model reproduces both geometries and charge transfer effects but requires time-consuming parametrization, especially for supramolecular systems containing repetitive units. To streamline this process, we introduce metallicious, a Python tool designed for efficient force-field parametrization of supramolecular structures. metallicious has been tested on diverse systems, including supramolecular cages, knots, and MOFs. Our benchmarks demonstrate that parameters obtained from metallicious accurately reproduce the reference properties obtained from quantum calculations and crystal structures. MD simulations of the generated structures consistently yield stable simulations in explicit solvent, in contrast to similar simulations performed with non-bonded and cationic dummy models. Overall, metallicious facilitates the setup of molecular dynamics (MD) of supramolecular systems simulations, providing insights into their dynamic properties and host-guest interactions. The tool is freely available on GitHub (https://github.com/duartegroup/metallicious) | Tomasz K. Piskorz; Bernadette Lee; Shaoqi Zhan; Fernanda Duarte | Theoretical and Computational Chemistry; Inorganic Chemistry; Supramolecular Chemistry (Inorg.); Transition Metal Complexes (Inorg.); Computational Chemistry and Modeling | CC BY 4.0 | CHEMRXIV | 2024-06-14 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/6669df63409abc03454349aa/original/metallicious-automated-force-field-parametrization-of-covalently-bound-metals-for-supramolecular-structures.pdf |
61e1975380719dab2b0f452a | 10.26434/chemrxiv-2022-lmskx-v2 | The Role of Homoaromaticity in the Tropylium-Catalyzed Carboxylic Acid O-H Insertion with Diazoesters | The tropylium catalyzed carboxylic acid O-H insertion with diazoesters providing α-hydroxy esters was reported recently through an activated carbene as the key intermediate. We report a revised mechanism involving a unique homoaromatic intermediate with the tropylium ion and the diazoester based on the DFT calculations. Our computational model provides a clear insight into the binding of the tropylium ion with the diazoester providing the homoaromatic intermediate. The reaction profiles of four different pathways were compared. The energies of the intermediates and the transition states are reported at B97-D3(SMD)/def2TZVP//B97-D3/def2TZVP (in dichloromethane). The energy profiles were compared across a few computational methods to study the sensitivity of our model across methods. | Anakuthil Anoop; Venkataraman Ganesh | Theoretical and Computational Chemistry; Organic Chemistry; Catalysis; Acid Catalysis; Homogeneous Catalysis; Organocatalysis | CC BY NC ND 4.0 | CHEMRXIV | 2022-01-17 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/61e1975380719dab2b0f452a/original/the-role-of-homoaromaticity-in-the-tropylium-catalyzed-carboxylic-acid-o-h-insertion-with-diazoesters.pdf |
62664426ed4d8843e417a487 | 10.26434/chemrxiv-2022-q929g-v2 | Permutation-Invariant-Polynomial Neural-Network-based Δ-Machine Learn-ing Approach: A Case for the HO2 Self-reaction and its Dynamics Study | The potential energy surface (PES) plays a central role in chemistry. As the size of the reaction system increases, it would be more and more difficult to develop its globally accurate full-dimensional PES. One unavoidable difficulty is that it is too expensive to calculate electronic energies of ample configurations for complicated reactions. Δ-machine learning is a highly cost-effective method as only a small number of high-level ab initio energies are required to improve a potential energy surface (PES) fit to a large number of low-level points. Here, we propose a permutation-invariant-polynomial neural-network (PIP-NN)-based Δ-machine learning approach to construct full-dimensional accurate PESs for complicated reactions. The approach is applied to the HO2 + HO2 → H2O2 + O2 reaction, a key process in combustion and atmosphere. The full-dimensional triplet state PES is constructed with a large number of density functional theory (DFT) points, which cover all dynamically relevant regions. Only 14% of the DFT dataset are used to successfully bring the DFT PES to the UCCSD(T)-F12a/AVTZ quality. On this PES of high quality, quasi-classical trajectory (QCT) calculations are performed to study the dynamics of the title reaction. A surprising mode-specific dynamics is observed, in which exciting a spectator mode leads to significant enhancement of the reactivity at low collision energy. This special mechanism can be attributed to increased attraction potential caused by the excited spectator mode. Such mode specificity may be quite prevalent in free radical reactions involving HO2, which is common in combustion and atmosphere. | Yang Liu; Jun Li | Theoretical and Computational Chemistry; Physical Chemistry; Computational Chemistry and Modeling; Theory - Computational; Machine Learning | CC BY NC ND 4.0 | CHEMRXIV | 2022-04-25 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/62664426ed4d8843e417a487/original/permutation-invariant-polynomial-neural-network-based-machine-learn-ing-approach-a-case-for-the-ho2-self-reaction-and-its-dynamics-study.pdf |
668c99605101a2ffa8cc8a90 | 10.26434/chemrxiv-2024-fl3ln | A DFT/MRCI Hamiltonian Parameterized Using Only Ab Initio Data: II. Core-Excited States | A newly parameterized combined density functional theory and multi-reference configuration interaction (DFT/MRCI) Hamiltonian, termed CVS-QE12, is defined for the computation of K-shell core-excitation and core-ionization energies. This CVS counterpart to the recently reported QE8 Hamiltonian [J. Chem. Phys, 160, 224106 (2024)] is parameterized by fitting to benchmark quality \textit{ab initio} data. The definition of the CVS-QE12 and QE8 Hamiltonians differ from previous CVS-DFT/MRCI parameterizations in three primary ways: (i) the replacement of the BHLYP exchange-correlation functional with QTP17 to yield a balanced description of both core and valence excitation energies, (ii) the adoption of a new, three-parameter damping function, and (iii) the introduction of separate scaling of the core-valence and valence-valence Coulombic interactions. Crucially, the parameters of the CVS-QE12 Hamiltonian are obtained via fitting exclusively to highly accurate ab initio vertical core-excitation and ionization energies computed at the CVS-EOM-CCSDT level of theory. The CVS-QE12 Hamiltonian is validated against further benchmark computations and is found to furnish K-edge core vertical excitation and ionization energies exhibiting absolute errors <=~0.5~eV at low computational cost. | Teagan Costain; Jibrael Rolston; Simon Neville; Michael Schuurman | Theoretical and Computational Chemistry; Computational Chemistry and Modeling; Theory - Computational | CC BY NC 4.0 | CHEMRXIV | 2024-07-10 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/668c99605101a2ffa8cc8a90/original/a-dft-mrci-hamiltonian-parameterized-using-only-ab-initio-data-ii-core-excited-states.pdf |
60c749014c8919734fad2ffb | 10.26434/chemrxiv.12009483.v1 | Nucleophilic (Radio)Fluorination of Redox-Active Esters via Radical-Polar Crossover Enabled by Photoredox Catalysis | <p>We report a redox-neutral method for nucleophilic fluorination of N-hydroxyphthalimide esters using an Ir photocatalyst under visible light irradiation. The method provides access to a broad range of aliphatic fluorides, including primary, secondary, and tertiary benzylic fluorides as well as unactivated tertiary fluorides, that are typically inaccessible by nucleophilic fluorination due to competing elimination. In addition, we show that the decarboxylative fluorination conditions are readily adapted to radiofluorination with [<sup>18</sup>F]KF. We propose that the reactions proceed by two electron transfers between the Ir catalyst and redox-active ester substrate to afford a carbocation intermediate that undergoes subsequent trapping by fluoride. Examples of trapping with O- and C-centered nucleophiles and deoxyfluorination via N-hydroxyphthalimidoyl oxalates are also presented, suggesting that this approach may offer a general blueprint for affecting redox-neutral SN1 substitutions under mild conditions.</p> | Eric Webb; John Park; Erin L. Cole; David J. Donnelly; Samuel Bonacorsi, Jr.; William R. Ewing; Abigail Doyle | Organic Synthesis and Reactions; Photocatalysis | CC BY NC ND 4.0 | CHEMRXIV | 2020-03-20 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/60c749014c8919734fad2ffb/original/nucleophilic-radio-fluorination-of-redox-active-esters-via-radical-polar-crossover-enabled-by-photoredox-catalysis.pdf |
60c758f1f96a001e85288f0f | 10.26434/chemrxiv.14621181.v1 | Profiling of Glycosphingolipids with SCDase Digestion and HPLC-FLD-MS | Lipid
components of cells and tissues feature a large diversity of structures that present
a challenging problem for molecular analysis. Glycolipids from mammalian cells
contain glycosphingolipids (GSLs) as their major glycolipid component, and
these structures vary in the identity of the glycan headgroup as well as the
structure of the fatty acid and sphingosine (Sph) tails. Analysis of intact
GSLs is challenging due to the low abundance of these species. Here, we develop
a new strategy for the analysis of lyso-GSL (<i>l</i>-GSL), GSL that retain
linkage of the glycan headgroup with the Sph base. The analysis begins with
digestion of a GSL sample with sphingolipid ceramide <i>N</i>-deacylase (SCDase), followed by labelling with an amine-reactive
fluorophore. The sample was then analyzed by HPLC-FLD-MS and quantitated by
addition of an external standard. This method was compared analysis of GSL
glycans after cleavage by an Endoglycoceramidase (EGCase) enzyme and labeling
with a fluorophore (2-anthranilic acid, 2AA). The two methods are complementary,
with EGCase providing improved signal (due to fewer species) and SCDase providing
analysis of lyso-GSL. Importantly the SCDase method provides Sph composition of
GSL species. We demonstrate the method on cultured human cells (Jurkat T cells)
and tissue homogenate (porcine brain). | Radhika Chakraberty; Bela Reiz; Christopher Cairo | Biochemistry; Chemical Biology | CC BY NC ND 4.0 | CHEMRXIV | 2021-05-21 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/60c758f1f96a001e85288f0f/original/profiling-of-glycosphingolipids-with-sc-dase-digestion-and-hplc-fld-ms.pdf |
6591003ae9ebbb4db91a7031 | 10.26434/chemrxiv-2024-dw6bb | Poly(L-glutamic acid) augments the transfection performance of lipophilic polycations by overcoming tradeoffs among cytotoxicity, pDNA delivery efficiency, and serum stability | Polycations are scalable and affordable nanocarriers for delivering therapeutic nucleic acids. Yet, cationicity-dependent tradeoffs between nucleic acid delivery efficiency, cytotoxicity, and serum stability hinder clinical translation. Typically, the most efficient polycationic vehicles also tend to be the most toxic. For lipophilic polycations—which recruit hydrophobic interactions in addition to electrostatic interactions to bind and deliver nucleic acids—extensive chemical or architectural modifications sometimes fail to resolve intractable toxicity-efficiency tradeoffs. Here, we demonstrate a facile post-synthetic polyplex surface modification strategy wherein with poly(L-glutamic acid) (PGA) rescues toxicity, inhibits hemolysis, and prevents serum inhibition of lipophilic polycation-mediated plasmid (pDNA) delivery. Importantly, the sequence in which polycations, pDNA, and PGA are combined dictates pDNA conformations and spatial distribution. Circular dichroism spectroscopy reveals that PGA must be added last to polyplexes assembled from lipophilic polycations and pDNA; else, PGA will disrupt polycation-mediated pDNA condensation. Although PGA did not mitigate toxicity caused by hydrophilic PEI-based polycations, PGA tripled the population of transfected viable cells for lipophilic polycations. Non-specific adsorption of serum proteins abrogated pDNA delivery mediated by lipophilic polycations; however, PGA-coated polyplexes proved more serum-tolerant than uncoated polyplexes. Despite lower cellular uptake than uncoated polyplexes, PGA-coated polyplexes were imported into nuclei at higher rates. PGA also silenced the hemolytic activity of lipophilic polycations. Our work provides fundamental insights into how polyanionic coatings transform intermolecular interactions between lipophilic polycations, nucleic acids, and serum proteins, and facilitate gentle yet efficient transgene delivery. | Ram Prasad Sekar; Jessica L. Lawson; Aryelle R.E. Wright; Caleb McGrath; Cesar Schadeck; Praveen Kumar; Jian Tay; Joseph Dragovan; Ramya Kumar | Materials Science; Polyelectrolytes - Materials | CC BY NC ND 4.0 | CHEMRXIV | 2024-01-02 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/6591003ae9ebbb4db91a7031/original/poly-l-glutamic-acid-augments-the-transfection-performance-of-lipophilic-polycations-by-overcoming-tradeoffs-among-cytotoxicity-p-dna-delivery-efficiency-and-serum-stability.pdf |
63483cb52a70913edf5b547a | 10.26434/chemrxiv-2022-61360-v3 | Expanding the Reactivity of Flavin Dependent Halogenases Toward Olefins via Enantioselective Intramolecular Haloetherification and Chemoenzymatic Oxidative Rearrangements | Of the different classes of halogenases characterized to date, flavin dependent halogenases (FDHs) are most commonly associated with site-selective halogenation of electron rich arenes and enol(ate) moieties in the biosynthesis of halogenated natural products. This capability has made them attractive biocatalysts, and extensive efforts have been devoted to both discovering and engineering these enzymes for different applications. We have established that engineered FDHs can catalyze different enantioselective halogenation processes, including halolactonization of simple alkenes with a tethered carboxylate nucleophile. In this study, we expand the scope of this reaction to include alcohol nucleophiles and a greater diversity of alkene substitution patterns to access a variety of chiral tetrahydrofurans. We also demonstrate that FDHs can be interfaced with ketoreductases to enable halocyclization using ketone substrates in one-pot cascade reactions and that the halocyclization products can undergo subsequent rearrangements to form novel hydroxylated and halogenated products. Together, these advances expand the utility of FDHs for enantio- and diastereoselective olefin functionalization. | Yuhua Jiang; Dibyendu Mondal; Jared Lewis | Biological and Medicinal Chemistry; Organic Chemistry; Catalysis; Organic Synthesis and Reactions; Stereochemistry; Biocatalysis | CC BY NC ND 4.0 | CHEMRXIV | 2022-10-14 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/63483cb52a70913edf5b547a/original/expanding-the-reactivity-of-flavin-dependent-halogenases-toward-olefins-via-enantioselective-intramolecular-haloetherification-and-chemoenzymatic-oxidative-rearrangements.pdf |
6671eb0e5101a2ffa8e63407 | 10.26434/chemrxiv-2024-jhbqx | A formal Fe(III/V) redox couple in an intercalation electrode | Iron is the most abundant transition metal in Earth’s crust, and redox cycling between its well-known low-valent oxidation states of FeII and FeIII drives crucial processes in nature. The FeII/III redox couple charge compensates cycling of lithium iron phosphate, a positive electrode (cathode) for lithium-ion batteries. High-valent iron redox couples, involving formal oxidation higher than FeIII, could deliver higher electrochemical potentials and energy densities. However, because of the instability of high-valent Fe electrodes, they have proven difficult to probe and exploit in intercalation systems. In this work, we report and characterize a formal FeIII/V redox couple by revisiting the charge compensation mechanism of (de)lithiation in Li4FeSbO6 (LFSO). Valence-sensitive experimental and computational core-level spectroscopy reveal a direct transition from FeIII (3d5) to a negative charge-transfer FeV (3d5L2) ground state upon delithiation, without forming FeIV. Exhibiting resistance to calendar aging, high operating potential, and low voltage hysteresis, the FeIII/V redox couple in LFSO provides a framework for developing sustainable, Fe-based intercalation cathodes for high-voltage applications. | Hari Ramachandran; Edward W. Mu; Eder G. Lomeli; Augustin Braun; Masato Goto; Kuan H. Hsu; Jue Liu; Zhelong Jiang; Kipil Lim; Grace M. Busse; Brian Moritz; Joshua J. Kas; John Vinson; John J. Rehr; Jungjin Park; Iwnetim I. Abate; Yuichi Shimakawa; Edward I. Solomon; Wanli Yang; William E. Gent; Thomas P. Devereaux; William C. Chueh | Theoretical and Computational Chemistry; Materials Science; Energy; Computational Chemistry and Modeling; Theory - Computational; Energy Storage | CC BY NC 4.0 | CHEMRXIV | 2024-06-19 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/6671eb0e5101a2ffa8e63407/original/a-formal-fe-iii-v-redox-couple-in-an-intercalation-electrode.pdf |
65e8847666c13817295857c2 | 10.26434/chemrxiv-2024-9qv8w | Active learning of alchemical adsorption simulations; towards a universal adsorption model. | Adsorption is a fundamental process studied in materials science and engineering because it plays a critical role in various applications, including gas storage and separation. Understanding and predicting gas adsorption within porous materials demands comprehensive computational simulations that are often resource intensive, limiting the identification of promising materials. Active learning (AL) methods offer an effective strategy to reduce the computational burden by selectively acquiring critical data for model training. Metal-organic frameworks (MOFs) exhibit immense potential across various adsorption applications due to their porous structure and their modular nature, leading to diverse pore sizes and chemistry that serve as an ideal platform to develop adsorption models. Here, we demonstrate the efficacy of AL in predicting gas adsorption within MOFs using “alchemical” molecules and their interactions as surrogates for real molecules. We first applied AL separately to each MOF, reducing the training dataset size by 57.5% while retaining predictive accuracy. Subsequently, we amalgamated the refined datasets across 1800 MOFs to train a multilayer perceptron (MLP) model, successfully predicting adsorption of real molecules. Furthermore, by integrating MOF features into the AL framework using principal component analysis (PCA), we navigated MOF space effectively, achieving high predictive accuracy with only a subset of MOFs. Our results highlight AL's efficiency in reducing dataset size, enhancing model performance, and offering insights into adsorption phenomenon in large datasets of MOFs. This study underscores AL's crucial role in advancing computational material science and developing more accurate and less data intensive models for gas adsorption in porous materials. | Etinosa Osaro; Fernando Fajardo-Rojas; Gregory Cooper; Diego Gómez-Gualdrón; Yamil Colón | Materials Science; Energy; Chemical Engineering and Industrial Chemistry | CC BY 4.0 | CHEMRXIV | 2024-03-08 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/65e8847666c13817295857c2/original/active-learning-of-alchemical-adsorption-simulations-towards-a-universal-adsorption-model.pdf |
60c757c0bdbb8971dea3ac6f | 10.26434/chemrxiv.14454291.v1 | Are Rate and Selectivity Correlated in Iridium-Catalysed Hydrogen Isotope Exchange Reactions? | Herein we examine the relationship between reaction rate and reaction selectivity in iridium-catalysed hydrogen isotope<br />exchange (HIE) reactions directed by Lewis basic functional groups. We have recently develped a directing group scale that allows semi-quantitative predictions of Lewis base directed selectivity in HIE, formally ranking ‘relative rates’ determined from a structured set of competition experiments. Here, we show that selectivity and rate are in fact not correlated, but that different types of behaviour emerge in competition experiments and that the observed behaviour can be predicted from our established selectivity scale. | Daria Timofeeva; David Lindsay; William Kerr; David Nelson | Organic Synthesis and Reactions; Physical Organic Chemistry; Homogeneous Catalysis; Bond Activation; Catalysis; Kinetics and Mechanism - Organometallic Reactions | CC BY NC ND 4.0 | CHEMRXIV | 2021-04-21 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/60c757c0bdbb8971dea3ac6f/original/are-rate-and-selectivity-correlated-in-iridium-catalysed-hydrogen-isotope-exchange-reactions.pdf |
62f5620ed62bc035f742709c | 10.26434/chemrxiv-2022-8j1df | Photoinduced Halogen-Atom Transfer (XAT) by N-heterocyclic carbene boryl radicals for C(sp3)−C(sp3) bond formation | In the realm of radical chemistry, halogen-atom transfer (XAT) is emerging as a powerful activation strategy in synthetic endeavors to engage otherwise recalcitrant organic halides. Although toxic tin radicals have been in the spotlight as halo-gen abstractors for decades, the era of photocatalysis has brought to light more sustainable options. Herein, we present a comprehensive study on the use of ligated boryl radicals to enable C(sp3)−C(sp3) bond forming reactions via XAT from alkyl halides. Two strategies have been developed using either direct light activation with near UV or photoredox conditions with visible light; both pivoting on N-heterocyclic carbene (NHC) boryl radicals. The present XAT strategy is very mild and accommodates a broad scope of alkyl halides, including medicinally-relevant compounds and biologically-active molecules. The key role of NHC boryl radicals in the operative reaction mechanism has been elucidated through a combination of ex-perimental, spectroscopic and computational studies. | Ting Wan; Luca Capaldo; Davide Ravelli; Walter Vitullo; Felix de Zwart; Bas de Bruin; Timothy Noel | Organic Chemistry; Catalysis; Organic Synthesis and Reactions; Photocatalysis; Redox Catalysis | CC BY 4.0 | CHEMRXIV | 2022-08-12 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/62f5620ed62bc035f742709c/original/photoinduced-halogen-atom-transfer-xat-by-n-heterocyclic-carbene-boryl-radicals-for-c-sp3-c-sp3-bond-formation.pdf |
67077562cec5d6c142c14ae5 | 10.26434/chemrxiv-2024-k44l1 | A New Look at Catalyst Surfaces at Work: introducing Mixed Isotope Operando Infrared Spectroscopy (MIOIRS) | This perspective focuses on the characterization of supported metal catalyst by operando and CO infrared (IR) spectroscopy. CO IR spectroscopy is a powerful technique to probe catalyst surfaces, and is used to identify single atom catalysts, estimate metal surface availability to the gas phase, and measure catalyst Lewis acidity. However, the interpretation of CO IR spectra on metal surfaces is not trivial, and influenced by dipole-dipole interactions among CO molecules at medium to high coverage. Such phenomenon results in spectral distortions, such as intensity transfer among IR bands, appearance of spurious bands, and shifts in band position. Dipole-dipole interactions have been widely investigated and understood in the 1950s–90s, but the implications for operando spectroscopy have been seemingly overlooked in literature, with a few exceptions. Inspired by seminal studies in the field, I propose here the use of mixed isotopic streams, such as diluted 13CO in 12CO, to reduce dipole coupling effects and retrieve more information from operando IR spectra in reactions involving CO, such as CO oxidation or hydrogenation reactions. Similarly, mixed 13CO2/12CO2 streams may be applied in CO2 hydrogenation, where adsorbed CO is commonly observed. The proposed name of the technique is Mixed Isotope Operando IR Spectroscopy, MIOIRS. In this perspective, I will first summarize the nature of dipole-dipole interactions in adsorbed CO layers, and their effects on CO IR spectra. Then, I will briefly describe how diluted isotopic mixtures of CO can partially break the coupling among adsorbates and reduce spectral distortion. In both sections, I will give a few showcases of the implications of vibrational coupling in heterogeneous catalysts characterization. Finally, I will discuss the possible implications of MIOIRS for the detection and quantification of defect and surface sites on metal nanoparticles, the characterization of bimetallic nanoparticles surfaces, and the kinetics of CO intermediates adsorbed on different active sites. Notably, MIOIRS may be expanded to other reactions in which adsorbates have strong permanent dipoles, such as in self-catalytic reduction for NOx abatement. | Matteo Monai | Catalysis; Heterogeneous Catalysis | CC BY NC ND 4.0 | CHEMRXIV | 2024-10-14 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/67077562cec5d6c142c14ae5/original/a-new-look-at-catalyst-surfaces-at-work-introducing-mixed-isotope-operando-infrared-spectroscopy-mioirs.pdf |
659d7e9366c138172913aa11 | 10.26434/chemrxiv-2023-cgrrj-v4 | A fast, convenient, polarizable electrostatic model for molecular dynamics | We present an efficient polarizable electrostatic model, utilizing typed, atom-centered, polarizabilities and the fast direct approximation, designed for efficient use in molecular dynamics (MD) simulations. The model provides two convenient approaches to assigning partial charges in the context of the atomic polarizabilities. One is a generalization of RESP, called RESP-dPol, and the other, AM1-BCC-dPol, is an adaptation of the widely used AM1-BCC method. Both are designed to accurately replicate gas-phase QM electrostatic potentials. Benchmarks of this polarizable electrostatic model against gas-phase dipole moments, molecular polarizabilities, bulk liquid densities, and static dielectric constants of organic liquids, show good agreement with the reference values. Of note, the model yields markedly more accurate dielectric constants of organic liquids, relative to a matched non-polarizable force field. MD simulations with this method, which is currently parameterized for molecules containing elements C, N, O, and H, run about only 3.6-fold slower than fixed charge force fields, while simulations with the self-consistent mutual polarization average 4.5-fold slower. Our results suggest that RESP-dPol and AM1-BCC-dPol afford improved accuracy, relative to fixed charge force fields, and are good starting points for developing general, affordable, and transferable polarizable force fields. The software implementing these approaches has been designed to utilize the force field fitting frameworks developed and maintained by Open Force Field Initiative, setting the stage for further exploration of this approach to polarizable force field development. | Liangyue Wang; Michael Schauperl; David L. Mobley; Christopher Bayly; Michael K. Gilson | Theoretical and Computational Chemistry; Computational Chemistry and Modeling | CC BY 4.0 | CHEMRXIV | 2024-01-10 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/659d7e9366c138172913aa11/original/a-fast-convenient-polarizable-electrostatic-model-for-molecular-dynamics.pdf |
65bcfbce9138d23161483f21 | 10.26434/chemrxiv-2024-tsfwf | Evaporation induced self-assembly of imogolite nanotubes in levitation: exploring phase transitions and material shaping | Evaporation-induced self-assembly (EISA) is a versatile method for generating organized superstructures from colloidal particles, offering diverse design possibilities through the manipulation of colloid size, shape, substrate nature, and environmental conditions. While some work highlighted the importance of the choice of the substrate, this parameter is often overlooked in many EISA studies. In this work, we compare the self-assembly of lyotropic liquid crystals by EISA on hydrophilic or hydrophobic substrates, and by acoustic levitation (absence of substrate). We focus on imogolite nanotubes, a model colloidal system of 1D charged objects, due to their tunable morphology and rich liquid-crystalline phase behavior. We demonstrate the feasibility to obtain phase transitions in levitating droplets and on hydrophobic substrate, whereas self-assembly was limited on hydrophilic supports. Moreover, the aspect ratio of the nanotubes proves to be a pivotal factor, influencing both transitions and the resulting materials shape and surface. Besides material shaping, acoustic levitation emerges as a promising method for studying phase transitions, toward the rapid establishment of phase diagrams from diluted to highly concentrated states using a limited volume of sample. | Claire Hotton; Thomas Bizien; Brigitte Pansu; Cyrille Hamon; Erwan Paineau | Physical Chemistry; Materials Science; Nanoscience; Liquid Crystals; Nanostructured Materials - Nanoscience; Self-Assembly | CC BY NC ND 4.0 | CHEMRXIV | 2024-02-05 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/65bcfbce9138d23161483f21/original/evaporation-induced-self-assembly-of-imogolite-nanotubes-in-levitation-exploring-phase-transitions-and-material-shaping.pdf |
6227f24d57a9d2462f783d64 | 10.26434/chemrxiv-2022-x647j | MACAW: an accessible tool for molecular embedding and inverse molecular design | The growing capabilities of synthetic biology and organic chemistry demand tools to guide syntheses towards useful molecules. Here, we present MACAW (Molecular AutoenCoding Auto-Workaround), a tool that uses a novel approach to generate molecules predicted to meet a desired property specification (e.g. a binding affinity of 50 nM or an octane number of 90). MACAW describes molecules by embedding them into a smooth multidimensional numerical space, avoiding uninformative dimensions that previous methods often introduce. The coordinates in this embedding provide a natural choice of features for accurately predicting molecular properties, which we demonstrate with examples for cetane and octane numbers, flash points, and histamine H1 receptor binding affinity. The approach is computationally efficient and well-suited to the small- and medium-size datasets commonly used in the biosciences. We showcase the utility of MACAW for virtual screening by identifying molecules with high predicted binding affinity to the histamine H1 receptor and limited affinity to the muscarinic M2 receptor, which are targets of medicinal relevance. Combining these predictive capabilities with a novel generative algorithm for molecules allows us to recommend molecules with a desired property value (i.e. inverse molecular design). We demonstrate this capability by recommending molecules with predicted octane numbers of 40, 80, and 120, which is an important characteristic for biofuels. Thus, MACAW augments classical retrosynthesis tools by providing recommendations for molecules on specification. | Vincent Blay; Tijana Radivojevic; Jonathan E. Allen; Corey M. Hudson; Hector Garcia-Martin | Theoretical and Computational Chemistry; Biological and Medicinal Chemistry; Computational Chemistry and Modeling; Machine Learning; Chemoinformatics - Computational Chemistry | CC BY NC 4.0 | CHEMRXIV | 2022-03-09 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/6227f24d57a9d2462f783d64/original/macaw-an-accessible-tool-for-molecular-embedding-and-inverse-molecular-design.pdf |
67da978d6dde43c90865d5c8 | 10.26434/chemrxiv-2025-c7zzr | BSE@GW-Based Protocol for Spin-Vibronic Quantum Dynamics Using the Linear Vibronic Coupling Model. Formulation and Application to an Fe(II) Compound | A protocol for generating potential energy surfaces and performing photoinduced nonadiabatic multidimensional wave packet propagation is presented. The workflow starts with the parameterization of a linear vibronic coupling (LVC) Hamiltonian using the BSE@GW approach. In a second step, the LVC model is used as input for multi-layer multi-configurational time-dependent Hartree (ML-MCTDH) wave packet propagation. To facilitate automated ML tree generation, a spectral clustering algorithm is applied based on a correlation matrix obtained from nuclear coordinate expectation values of a full-dimensional Time-dependent Hartree (TDH) simulation. The performance of the protocol is tested on the photoinduced spin-vibronic dynamics of a transition metal complex, [Fe(cpmp)]$^{+2}$. For this example, it is shown that BSE@GW provides a more robust description of the character of the transitions contributing to the absorption spectrum compared to TD-DFT. Furthermore, the LVC parameterization is tested against explicit calculations of potential energy curves to find the validity of the linear approximation over a wide range of normal mode elongation. Finally, the flexibility of spectral clustering is used to generate different ML trees, resulting in very different numerical efficiencies for ML-MCTDH propagation. In terms of electronic structure and dimensionality, [Fe(cpmp)]$^{+2}$ is a challenging example, suggesting that the new protocol should be applicable to a wide range of systems. | Florian Bogdain; Sebastian Mai; Leticia Gonzalez; Oliver Kuehn | Theoretical and Computational Chemistry; Computational Chemistry and Modeling; Theory - Computational | CC BY 4.0 | CHEMRXIV | 2025-03-20 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/67da978d6dde43c90865d5c8/original/bse-gw-based-protocol-for-spin-vibronic-quantum-dynamics-using-the-linear-vibronic-coupling-model-formulation-and-application-to-an-fe-ii-compound.pdf |
64f5862779853bbd780e7002 | 10.26434/chemrxiv-2023-qdvdk | Selectivity of Grignard reagent formation – from semi-batch to continuous lab and pilot scale | The formation of Grignard reagents from metallic magnesium and a halide is often accompanied by the formation of the Wurtz coupling product, an undesired side product formed by the reaction of a Grignard reagent molecule and a halide molecule. By using a scale-up approach from semi-batch type synthesis to continuous lab and pilot scale for various Grignard reagents, it is demonstrated that a continuous production process can improve Grignard reagent selectivity and reduce Wurtz coupling. | Eva Deitmann; Kai Dahms; Michael Maskos; Dirk Ziegenbalg; Gabriele Menges-Flanagan | Organic Chemistry; Organometallic Chemistry; Chemical Engineering and Industrial Chemistry; Organic Synthesis and Reactions; Process Chemistry; Reaction (Organomet.) | CC BY NC ND 4.0 | CHEMRXIV | 2023-09-05 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/64f5862779853bbd780e7002/original/selectivity-of-grignard-reagent-formation-from-semi-batch-to-continuous-lab-and-pilot-scale.pdf |
6642271f91aefa6ce1de1b8f | 10.26434/chemrxiv-2024-qv0gd | Electrochemical Synthesis of Added Valuable Purine Alkaloid Metabolites from Caffeine Feedstock Employing a Structure Electro-Activity Relationship (SeAR) Approach | The development of electrochemical approaches to the valorization of abundant natural products into high value medications and metabolites is of pharmaceutical interest. In this study, we explored the electrosynthetic behavior of the abundant legal psychoactive, caffeine, a representative member of the purine alkaloid class. Initial screening of the cyclic voltammetric behavior of eleven exemplar purine alkaloids revealed a predicted structure electroactivity relationship (SeAr). Optimization of the current controlled electrochemical (CCE) reaction informed by cyclic voltammetry measurements enabled the dialing-in/out of differential oxidative metabolic products. Sequential desmethylation around the purine ring was observed both by isolation and comparison of reference standards using HPLC. Amide, imide, and a novel N-methyl heteroaryl oxidation mechanism are observed. Tractable quantities of the high-value theophylline (medication) and paraxanthine (dietary supplement) were isolated in 17% and 8% b.r.s.m. employing an electrolyte recovery strategy. This approach offers a marked improvement compared to other approaches (chemical 0.8% and enzymatic 0.97% yields) and may have potential in other natural product and drug discovery settings. | Ridho Asra; Alan Jones | Physical Chemistry; Biological and Medicinal Chemistry; Organic Chemistry; Natural Products; Drug Discovery and Drug Delivery Systems; Electrochemistry - Mechanisms, Theory & Study | CC BY 4.0 | CHEMRXIV | 2024-06-13 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/6642271f91aefa6ce1de1b8f/original/electrochemical-synthesis-of-added-valuable-purine-alkaloid-metabolites-from-caffeine-feedstock-employing-a-structure-electro-activity-relationship-se-ar-approach.pdf |
6329ac8108470020f4826ae8 | 10.26434/chemrxiv-2022-z1xzk | Gas-particle flow of pneumatic conveying in vertical pipes simulated using four-way coupled second-order moment method | Gas-particle flow in vertical pipes and its anisotropic behavior of turbulence were investigated using the novel four-way coupled second-order moment method of the fluid-particle Eulerian–Eulerian two-fluid model. In this study, the flow behavior of a gas-particle two-phase flow in a vertical pipe was simulated. The study investigated the gas turbulence affected by the presence of particles. For instance, the enhancement of the gas turbulence due to the presence of particles having a diameter of 500 µm, causing wake shedding and the dissipation of particle fluctuation was predicted by the effect of the fluid-particle and particle-particle interactions. Furthermore, the anisotropic turbulence of the gas phase was also predicted to be enhanced by the presence of 500-µm particles, wherein the anisotropic ratio of the second-order moment of the gas phase turbulent velocity was predicted to be in the range of 2–12. Contrarily, in the presence of smaller particles with a diameter of 200 µm, the anisotropic turbulence of the gas phase was predicted to be attenuated, and the anisotropic ratio was reduced to the range of 1–2. In addition, the absolute value of the turbulence dissipation of particles due to fluid-particle interactions was predicted to be half of that due to particle collisions. The anisotropic behavior of these turbulence dissipations was predicted close to the anisotropic behavior of particle turbulence in both the distribution and value. | Dan Sun | Chemical Engineering and Industrial Chemistry; Fluid Mechanics; Transport Phenomena (Chem. Eng.) | CC BY NC ND 4.0 | CHEMRXIV | 2022-09-21 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/6329ac8108470020f4826ae8/original/gas-particle-flow-of-pneumatic-conveying-in-vertical-pipes-simulated-using-four-way-coupled-second-order-moment-method.pdf |
60c74ba8bdbb893c5ba3961d | 10.26434/chemrxiv.12370406.v1 | Ferro-Self-Assembly: Magnetic and Electrochemical Adaptation of a Multiresponsive Zwitterionic Metalloamphiphile Showing a Shape-Hysteresis Effect | We report on a novel multi-stimuli-responsive amphiphile, 1-(<i>Z</i>)-heptenyl-1’-dimethylammonium-methyl-(3-sulfopropyl)ferrocene<b>
</b>(<b>6</b>), whose self-assembly properties can be altered by three different stimuli, namely: (i) the addition of external salts which serve to unfold the sultone headgroup, thus triggering self-assembly of <b>6</b> into vesicles; (ii) oxidation to <b>6<sup>+</sup></b>, which changes the lipophilic ferrocene to a hydrophilic ferrocenium entity, thereby broadening the size-distribution of the aggregates; and (iii) exposition of <b>6<sup>+</sup> </b>to an external magnetic field of 0.8 T. Under thease conditions and at sufficient concentration, <b>6</b><sup><b>+</b> </sup>forms large, tubular aggregates with lengths of up to 15 µm, which persist for over 5 min after the field is switched off again. <b>6<sup>+</sup></b> is thus the first amphiphile to exhibit a shape-hysteresis effect. The self-assembly/disassembly processes and their dynamics were studied live and in situ by optical birefringence measurements coupled to light scattering. <br /> | Stefan Bitter; Moritz Schlötter; Markus Schilling; Rainer Winter; Sebastian Polarz | Aggregates and Assemblies | CC BY NC ND 4.0 | CHEMRXIV | 2020-05-27 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/60c74ba8bdbb893c5ba3961d/original/ferro-self-assembly-magnetic-and-electrochemical-adaptation-of-a-multiresponsive-zwitterionic-metalloamphiphile-showing-a-shape-hysteresis-effect.pdf |
6696ad13c9c6a5c07a750d00 | 10.26434/chemrxiv-2024-6qc19 | Detailed Structural Elucidation of an Antibody-Drug Conjugate, AZD8205, Biotransformation Species Using LC-MRM with CID and EAD Fragmentation | Antibody-drug conjugates (ADC) are a promising drug modality experiencing substantial expansion in both discovery space and clinical development, due to its targeted delivery and potentially improved therapeutic index. Assessing the biotransformation of ADCs in vitro and in vivo is important in understanding their stability and pharmacokinetic properties. We have previously reported biotransformation pathways for the anti-B7H4 topoisomerase I inhibitor ADC, AZD8205, that underpin its structural stability in vivo using intact protein mass LC-HRMS approach. Herein we employed LC-MRM method with both CID and EAD fragmentation that confirmed our earlier findings. Furthermore, we were able to obtain additional detailed structural information of these biotransformation products expanding on earlier intact mass method analyses. We also highlight the high sensitivity of LC-MRM for successfully identifying minor biotransformation products at low concentrations, that were not distinguishable using the intact mass LC-HRMS workflow. Especially, the EAD fragmentation aided in the confirmation of biotransformation species that contain newly formed disulfide bonds, due to the preferential fragmentation of disulfide bonds using this method. We observed biotransformation reactions that vary between linker-payload (PL) conjugation sites on the antibody, including the trend towards constitutional isomerism in thio-succinimide linker hydrolysis, and linker-payload deconjugation. The reported orthogonal analytical approach highly complements and fortifies the earlier findings from intact protein mass LC-HRMS explaining AZD8205 stability in vivo. This study sheds further light upon detailed structural confirmation of ADC biotransformation and validates our earlier findings that explain AZD8205 stability in vivo. | Junyan Yang; Hui Yin Tan; Jiaqi Yuan; Yue Huang; Anton Rosenbaum | Analytical Chemistry; Mass Spectrometry | CC BY 4.0 | CHEMRXIV | 2024-07-17 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/6696ad13c9c6a5c07a750d00/original/detailed-structural-elucidation-of-an-antibody-drug-conjugate-azd8205-biotransformation-species-using-lc-mrm-with-cid-and-ead-fragmentation.pdf |
66a07bb05101a2ffa8cc83ad | 10.26434/chemrxiv-2024-4563v | Digital Twin for Chemical Sciences (DTCS): A Blueprint for Digitizing Chemical Characterization | Directly visualizing chemical trajectories offers novel insights into catalysts, gas phase reactions, photo-induced dynamics, and quantum information processing. Identifying and tracking the exchange of matter to observe the creation and annihilation of chemical species is best achieved by closely coupling theory and experiment. We developed Digital Twin for Chemical Science (DTCS) v.01, a platform that mimics advanced characterization instruments, including those at Scientific User Facilities. DTCS v.01 addresses challenges in data acquisition, analysis, and model-driven interpretation via a physics-based, AI-accelerated approach. We validated this concept with ambient pressure X-ray Photoelectron Spectroscopy (APXPS) observations using a ubiquitous metal-water interfacial scenario, i.e., Ag/H2O, as a representative example. The inputs of DTCS v.01 are designed to mirror the experimental chemists' workflows, and the outputs can be directly compared to and are constantly updated from the experimental data. This integrated theoretical and experimental platform enhances user accessibility and facilitates the acquisition of standardized mechanistic insights. | Jin Qian; Asmita Jana; Siddarth Menon; Andrew Bogdan; Rebecca Hamlyn; Johannes Mahl; Ethan J. Crumlin | Analytical Chemistry; Energy; Chemoinformatics; Spectroscopy (Anal. Chem.); Materials Chemistry | CC BY NC ND 4.0 | CHEMRXIV | 2024-07-24 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/66a07bb05101a2ffa8cc83ad/original/digital-twin-for-chemical-sciences-dtcs-a-blueprint-for-digitizing-chemical-characterization.pdf |
60c7504c469df48230f4484b | 10.26434/chemrxiv.13014371.v1 | Regioselective Dehydration of Sugar Thioacetals under Mild Conditions | Pentose
and hexose sugars are abundant constituents of waste biomass, making them
sustainable, chiral building blocks for organic synthesis. The demand for
chiral saturated heterocyclic rings from the pharmaceutical industry is
increasing as they provide well-defined three-dimensional frameworks that show
increased metabolic resistance. Through the formation of thioacetals, sugars may
be manipulated in their straight-chain form and dehydrated selectively under
basic conditions at C-2. This approach was applied to an array of sugars and
extended to the production of useful chiral THFs via further selective
dehydration reactions. | Rachel Szpara; Alexander Goyder; Michael Porter; Helen Hailes; Tom Sheppard | Natural Products; Organic Synthesis and Reactions; Stereochemistry | CC BY 4.0 | CHEMRXIV | 2020-09-29 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/60c7504c469df48230f4484b/original/regioselective-dehydration-of-sugar-thioacetals-under-mild-conditions.pdf |
647131b5e64f843f41d4228c | 10.26434/chemrxiv-2023-6j38m-v3 | Ambient catalyst free nitrogen fixation with water dimer radical cation | The growth and sustainable development of humanity is heavily dependent upon the process of fixing nitrogen (N2) to ammonia (NH3). However, the currently adopted methods are associated with severe environmental hazards and tremendous energy costs, which limit their sustainability and profitability. Herein we discovered a catalyst-free disproportionation reaction of N2 by water dimer radical cation, (H2O)2+•, which occurs under mild ambient conditions via distinctive HONH-HNOH+• intermediate to yield economically valuable nitroxyl (HNO) and hydroxylamine (NH2OH) products, in alternative to NH3. Calculations suggest that the reaction is prompted by the coordination of electronically excited N2 with (H2O)2+• in its two-center-three-electron (2c-3e) configuration. Subsequent excited-state double proton transfer leads to one-step water addition to N2. The ambient fixation of N2 into HNO and NH2OH with high selectivity offers great profitability and total avoidance of polluting emissions, such as CO2 or NOy, thus giving an entirely new look and perspectives to the problem of green N2 fixation. | Xiaoping Zhang; Liping Huang; Jingling Li; Wenwen Yang; Konstantin Chingin; Roman Balabin; Jingjing Wang; Xinglei Zhang; Weifeng Zhu; Rui Su; Keke Huang; Shouhua Feng; Huanwen Chen | Physical Chemistry; Analytical Chemistry; Chemical Engineering and Industrial Chemistry; Mass Spectrometry; Spectroscopy (Anal. Chem.); Thermodynamics (Physical Chem.) | CC BY NC ND 4.0 | CHEMRXIV | 2023-05-29 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/647131b5e64f843f41d4228c/original/ambient-catalyst-free-nitrogen-fixation-with-water-dimer-radical-cation.pdf |
67db833281d2151a021a523f | 10.26434/chemrxiv-2025-58n67 | Omniligase-1 mediated peptide cyclization for phage display | We report an enzymatic cyclization strategy, termed omniligase-1 mediated peptide bicyclization. Electrophilic group was introduced into the recognition sequence of omniligase to achieve intramolecular bicyclization with Cys residues. Combined with phage display, we identified a bicyclic peptide ligand targeting TEAD4 with a KD value of 1.5 µM, 100-fold lower than its linear version, demonstrating the utility of this platform for discovering bicyclic peptide ligands. | Gemin Fang; Xiaocui Wan; Wenjing Zhu; Huimin Wei; Yanni Zhang; Fenghao Zheng; Hua Zhang; Ying Chen; Junhao Xue; Yuxuan Wang | Biological and Medicinal Chemistry | CC BY NC ND 4.0 | CHEMRXIV | 2025-03-21 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/67db833281d2151a021a523f/original/omniligase-1-mediated-peptide-cyclization-for-phage-display.pdf |
60c73cc9702a9b6e4b189aa6 | 10.26434/chemrxiv.14742879.v1 | On-Surface Synthesis of Variable Bandgap Nanoporous Graphene | <p>Tuning the bandgap of nanoporous graphene
is desirable for applications such as the charge transport layer in
organic-hybrid devices. The holy grail in the field is the ability to
synthesize 2D nanoporous graphene with variable pore sizes, and hence tuneable band
gaps. Herein, we demonstrate the on-surface synthesis of nanoporous graphene
with variable bandgaps. Two types of nanoporous graphene were synthesized via
hierarchical C-C coupling, and verified by low-temperature scanning tunneling
microscopy and non-contact atomic force microscopy with CO-terminated tip. Nanoporous
graphene-1 is non-planar, and nanoporous graphene-2 is a single-atom thick
planar sheet. Scanning tunneling spectroscopy measurements reveal that nanoporous
graphene-2 has a bandgap of 3.8 eV, while nanoporous graphene-1 has a larger
bandgap of 5.0 eV. Corroborated by first-principles calculations, we propose
that the large bandgap opening is governed by the confinement of π-electrons
induced by pore generation or the non-planar structure, and can be explained by
Clar sextet theory. Our finding shows that by introducing nanopores, semimetallic
graphene is converted into semiconducting nanoporous graphene-2 or insulating
wide-bandgap nanoporous graphene-1. </p><br /> | Dingguan Wang; Arramel Arramel; Xuefeng Lu; Yang Ming; Jishan Wu; Andrew Wee | Nanostructured Materials - Nanoscience | CC BY NC ND 4.0 | CHEMRXIV | 2021-06-08 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/60c73cc9702a9b6e4b189aa6/original/on-surface-synthesis-of-variable-bandgap-nanoporous-graphene.pdf |
60c748810f50dbb44d396799 | 10.26434/chemrxiv.11535027.v2 | Paper-Based Low Cost Optical Filter | <p>We report simple and inexpensive technique using several sheets of white paper for filtering the blue and non-blue radiation of a white light emitting diode source in the transmission mode. We visibly illustrate successful rejection of specific energy of white light by the filtering papers through absorption mechanism where weak transmission of blue and red radiations are observed. In addition, photoluminescence arising from the papers in near infrared region is also presented while using the white light excitation. Owing to the presence of different whitening agents in the papers, selective absorption and divergent coloured emission from the sheets are observed.</p> | Ajay Tripathi; Rajesh Rawat; Archana Tiwari | Optical Materials | CC BY NC ND 4.0 | CHEMRXIV | 2020-02-20 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/60c748810f50dbb44d396799/original/paper-based-low-cost-optical-filter.pdf |
66f433c812ff75c3a17075ff | 10.26434/chemrxiv-2024-mbk38 | Physics-informed dual-objective optimization of high-entropy-alloy nanozymes by a robotic AI chemist | Engineering artificial nanozymes as substitutes for natural enzymes presents a significant scientific challenge. High entropy alloys (HEAs) have emerged as promising candidates for mimicking peroxidase (POD) activity thanks to their unique properties and versatility. However, designing or discovering HEAs that surpass the catalytic efficiency of natural horseradish peroxidase involves complex challenges, often hindered by the multidimensional nature of HEAs’ compositional variability and the intricate interplay of enzymatic behaviours. Therefore, an intelligent and efficient approach to accelerate this discovery is crucial. In this study, we address these challenges by deploying a robotic artificial-intelligence chemist equipped with theoretical calculations, machine learning, Bayesian optimization, and on-the-fly data analysis by a large language model (LLM). Our approach centres on a physics-informed, multi-objective optimization framework that simultaneously optimizes multiple desirable properties of nanozymes, including maximum reaction rate and substrate affinity, ultimately optimizing catalytic efficiency. By integrating an auxiliary knowledge model based on physical insights and collaborative decision-making enabled by LLM-in-the-loop into Bayesian optimization, we enhanced the data-driven discovery workflow. Our physics-informed approach, with instant LLM-in-the-loop feedback, significantly outperformed both random sampling and standard Bayesian optimization. Consequently, we efficiently explored a vast chemical space and identified HEAs with enzymatic properties that significantly exceed those of the most effective catalysts based on HEAs or single atoms reported in the literature, as well as the natural enzyme. | Man Luo; Zikai Xie; Huirong Li; Baicheng Zhang; Jiaqi Cao; Yan Huang; Qing Zhu; Linjiang Chen; Jun Jiang; Yi Luo | Theoretical and Computational Chemistry; Physical Chemistry; Materials Chemistry | CC BY NC ND 4.0 | CHEMRXIV | 2024-09-27 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/66f433c812ff75c3a17075ff/original/physics-informed-dual-objective-optimization-of-high-entropy-alloy-nanozymes-by-a-robotic-ai-chemist.pdf |
619672772e10ad30154bb93c | 10.26434/chemrxiv-2021-sj4p5 | Effect of Exterior Home Renovation on Community Lead Hazards: A Pilot Study in South Bend, Indiana | Communities across the US face challenges from legacy lead contamination. In South Bend, Indiana, over 68,000 homes were built before 1978, and most contain leaded paint. When these homes are repainted, repaired, or renovated, failure to use lead-safe practices can contaminate the surrounding soil with lead paint flakes and dust. In this study, we used X-ray fluorescence (XRF) to measure soil lead levels surrounding a home with exterior leaded paint (about 10% Pb w/w) after it was repainted in fall of 2019. The painted wooden exterior was prepared for painting by dry scraping without the use of tarps or plastic barriers. A total of 220 soil samples were collected from the home and its immediate neighbors, and an additional 102 samples were collected from 34 homes in the same neighborhood. The median lead level in dripline soil samples across the neighborhood was 434 ppm, but in the recently repainted house, the median soil lead was 1808.9 ppm, and it was 1,346.4 ppm in the four neighboring homes. The repainted house and its four neighbors were mulched by covering all bare soil to a 4-6 inch depth with chipped wood mulch. Two months later, another 100 soil samples were collected and analyzed. The surface lead level around the target house dropped to 13.8 ppm, showing that mulching is an effective strategy for interim control of high soil lead levels. | Kyle Moon; Meghanne Tighe; Joshua Brooks; J. Mike Coman; Heidi Beidinger-Burnett; Matthew Sisk; Marya Lieberman | Analytical Chemistry; Earth, Space, and Environmental Chemistry; Wastes; Environmental Analysis | CC BY NC ND 4.0 | CHEMRXIV | 2021-11-19 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/619672772e10ad30154bb93c/original/effect-of-exterior-home-renovation-on-community-lead-hazards-a-pilot-study-in-south-bend-indiana.pdf |
657ffd70e9ebbb4db92ba06f | 10.26434/chemrxiv-2023-hnvw4 | Effect of Pre-Damage on the Fracture Energy of Double-Network Hydrogels | Double-network (DN) hydrogels are tough soft materials and the high fracture resistance can be attributed to the formation of a large damage zone (internal fracture of the brittle first network) around the crack tip. In this work, we studied the effect of pre-damage in the brittle network on the fracture energy Γc of DN hydrogels. The pre-damage of the first network was induced by pre-stretching the DN gels to prestretch ratio λpre. Depending on the λpre in relative to the yielding stretch ratio λy, above which the brittle first network starts to break into discontinuous fragments inside DN gels, two regimes were observed: Γc decreases monotonically with λpre in the regime of λpre < λy, mainly due to the decreasing contribution from the bulk internal damage; while Γc increases with λpre in the regime of λpre > λy, The latter can be understood by the release of hidden length of the stretchable network strands by the rupture of the brittle network, whereby the broken fragments of brittle network could serve as sliding crosslinks to further delocalize the stress concentration near the crack tip and prevent chain scissions. | Yong Zheng; Yiru Wang; Tasuku Nakajima; Jian Ping Gong | Polymer Science; Hydrogels | CC BY NC ND 4.0 | CHEMRXIV | 2023-12-20 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/657ffd70e9ebbb4db92ba06f/original/effect-of-pre-damage-on-the-fracture-energy-of-double-network-hydrogels.pdf |
60c755d5469df4bd9af451e8 | 10.26434/chemrxiv.14173427.v1 | Base-Mediated Generation of Ketenimines from Ynamides: Addition of Hydrazones to Give Acetimidohydrazides | Under basic conditions, N-arylketenimines were generated in situ from N-Boc ynamides and reacted with hydrazones. Under heating, an addition of the hydrazone onto the central carbon of the ketenimine takes place, giving rise to various acetamidohydrazides.<br /> | Capucine Mahe; Agathe C. A. D’Hollander; Kevin Cariou | Organic Synthesis and Reactions | CC BY NC ND 4.0 | CHEMRXIV | 2021-03-08 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/60c755d5469df4bd9af451e8/original/base-mediated-generation-of-ketenimines-from-ynamides-addition-of-hydrazones-to-give-acetimidohydrazides.pdf |
64be4320ae3d1a7b0d3f32dc | 10.26434/chemrxiv-2023-n0l8n | Amino acids as chelating ligands for platinum: enhanced stability in aqueous environment promoted by biocompatible molecules
| Platinum (II) based chemotherapeutics are a cornerstone in the treatment of many malignancies. However,
their severe toxicity and dose-limiting side-effects have rooted efforts in the medicinal inorganic community
to develop better drug candidates with higher selectivity for tumor tissues and less problematic side effects.
In the current study, we developed a cytotoxic platinum (II) complex based on a Zeise’s salt substructure
containing the nonsteroidal anti-inflammatory drug (NSAID) acetylsalicylic acid (ASA) as a ligand. Since the
original complex displayed high reactivity against sulfur-containing biomolecules, the structure was
optimized regarding its stability. Amino acids L-alanine, β-alanine and L-histidine were used as biocompatible
chelating ligands to achieve this aim. Differences in the coordination sphere caused pronounced changes in
the stability profiles of the Zeise-type precursor complexes 1-3. Of the tested systems, coordination with LAla through N in trans position to ethylene (N-trans) showed the most promising results and was employed
to stabilize the previously published complex 5. The stability profiles of all complexes were evaluated by
capillary electrophoresis and the biological activity was investigated in vitro in various tumor cell lines. To
investigate the effect of the NSAID ligand on the mode-of-action, inhibition of cyclooxygenase enzymes was
also tested. Platinum (II) complex 4 containing both the ASA and the Ala ligand showed improved stability
and higher cytotoxicity, outperforming both 5 and 1, exhibiting a cytotoxic activity at 25 µM comparable to
the reference drug cisplatin. | Andrea Cucchiaro; Amelie Scherfler; Davide Corinti; Giel Berden; Jos Oomens; Klaus Wurst; Ronald Gust; Maria Elisa Crestoni; Brigitte Kircher; Monika Cziferszky | Biological and Medicinal Chemistry; Inorganic Chemistry; Organometallic Chemistry; Drug Discovery and Drug Delivery Systems; Bioorganometallic Chemistry; Crystallography – Inorganic | CC BY NC 4.0 | CHEMRXIV | 2023-07-25 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/64be4320ae3d1a7b0d3f32dc/original/amino-acids-as-chelating-ligands-for-platinum-enhanced-stability-in-aqueous-environment-promoted-by-biocompatible-molecules.pdf |
60c73cc0842e651b1bdb167f | 10.26434/chemrxiv.14748840.v1 | Synthesis of a Biomimetic Tetracyclic Precursor of Aspochalasins Allowing a Formal Synthesis of Trichoderone A | Aspochalasins
are leucine-derived cytochalasins. Their complexity is often associated to a
high degree of biosynthetic oxidative transformations that could inspire a
two-phase strategy in total synthesis. In that context, we describe the
synthesis of a putative biomimetic tetracyclic intermediate. The key
constructive steps are an intramolecular Diels-Alder reaction to install the
characteristic isoindolone core of cytochalasins, whose branched precursor was
obtained from a stereoselective Ireland-Claisen rearrangement made on a highly
unsaturated substrate. This work also constitutes a formal synthesis of
trichoderone A. | Oscar Gayraud; Benjamin Laroche; Nicolas Casaretto; Bastien Nay | Natural Products; Organic Synthesis and Reactions | CC BY NC ND 4.0 | CHEMRXIV | 2021-06-09 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/60c73cc0842e651b1bdb167f/original/synthesis-of-a-biomimetic-tetracyclic-precursor-of-aspochalasins-allowing-a-formal-synthesis-of-trichoderone-a.pdf |
67d45bb181d2151a02600e0a | 10.26434/chemrxiv-2025-qj4k3 | Molecular deep learning at the edge of chemical space | Molecular machine learning models often fail to generalize beyond the chemical space of their training data, limiting their ability to reliably perform predictions on structurally novel bioactive molecules. To advance the ability of machine learning to go beyond the ‘edge’ of their training chemical space, we introduce a joint modeling approach that combines molecular property prediction with molecular reconstruction, enabling us to estimate model generalizability through a new reconstruction-based ‘unfamiliarity’ metric. Via a systematic analysis spanning more than 30 bioactivity datasets, we demonstrate that unfamiliarity not only effectively identifies out-of-distribution molecules but also serves as a reliable predictor of classifier performance. Even when faced with the presence of strong distribution shifts, unfamiliarity yields robust and meaningful molecular insights that go unnoticed by traditional methods. Our findings highlight that joint modelling can be a powerful strategy for extending the reach of machine learning models into uncharted regions of chemical space, advancing the discovery of diverse and novel molecules. | Derek van Tilborg; Luke Rossen; Francesca Grisoni | Theoretical and Computational Chemistry; Biological and Medicinal Chemistry; Machine Learning; Artificial Intelligence; Chemoinformatics - Computational Chemistry | CC BY NC 4.0 | CHEMRXIV | 2025-03-17 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/67d45bb181d2151a02600e0a/original/molecular-deep-learning-at-the-edge-of-chemical-space.pdf |
641b9ec92bfb3dc25133acb2 | 10.26434/chemrxiv-2023-h18vl | Generating signals at converging liquid fronts to create line-format readouts of soluble assay products in three-dimensional paper-based devices | The correct interpretation of the result from a point-of-care device is crucial for an accurate and rapid diagnosis and to guide subsequent treatment. Lateral flow tests (LFTs) use a well- established format that was designed to simplify the user experience. However, the LFT device architecture is inherently limited to detecting analytes that can be captured by molecular recognition. Microfluidic paper-based analytical devices (μPADs), like LFTs, have the potential to be used in diagnostic applications at the point of care. However, μPADs have not gained significant traction outside of academic laboratories, in part, because they have often demonstrated a lack of homogeneous shape or color in signal outputs, which consequently can lead to inaccurate interpretation of results by users. Here, we demonstrate a new class of μPADs that generate colorimetric signals at the interfaces of converging liquid fronts (i.e., lines) to control where colorimetric signals are formed without relying on capture techniques. We demonstrate our approach by developing assays for three classes of analytes—an ion, an enzyme, and a small molecule—using iron (III), acetylcholinesterase, and lactate, respectively. Additionally, we show these devices have the potential to support multiplexed assays by generating multiple lines in a common readout zone. These results highlight the ability of this new paper-based device architecture to aid the interpretation of assays that create soluble products by using flow to constrain those colorimetric products in a familiar, line-format output. | Ibrahim Abdullah; Daniel J. Wilson; Andrea C. Mora; Rayleigh W. Parker; Charles R. Mace | Analytical Chemistry; Analytical Chemistry - General; Biochemical Analysis; Materials Chemistry | CC BY NC ND 4.0 | CHEMRXIV | 2023-03-23 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/641b9ec92bfb3dc25133acb2/original/generating-signals-at-converging-liquid-fronts-to-create-line-format-readouts-of-soluble-assay-products-in-three-dimensional-paper-based-devices.pdf |
65f0978fe9ebbb4db991888a | 10.26434/chemrxiv-2024-58tt1-v2 | Efficient acceleration of the convergence of the Minimum Free Energy Path via path-planning generated initial guess | We demonstrate how the combination of a shifted clustering algorithm and a fast-marching- based algorithm is able to generate good approximations of the Minimum Free Energy Path (MFEP) if a Free Energy Landscape (FEL) is given. Then, we show that using this kind of approximation as the MFEP’s first guess and the string method for further refinement (also called the FMT-string combined approach) cuts down on the number of iterations needed for the MFEP to converge by a large amount. This saves a lot of time compared to using a linear interpolation as the first guess. Such a method provides an efficient alternative to the growing string method for obtaining a good initial guess of the MFEP. | Yi Sun | Theoretical and Computational Chemistry; Computational Chemistry and Modeling | CC BY 4.0 | CHEMRXIV | 2024-03-13 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/65f0978fe9ebbb4db991888a/original/efficient-acceleration-of-the-convergence-of-the-minimum-free-energy-path-via-path-planning-generated-initial-guess.pdf |
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