id
stringlengths 24
24
| doi
stringlengths 28
32
| title
stringlengths 8
495
| abstract
stringlengths 17
5.7k
| authors
stringlengths 5
2.65k
| categories
stringlengths 4
700
| license
stringclasses 3
values | origin
stringclasses 1
value | date
stringdate 1970-01-01 00:00:00
2025-03-24 00:00:00
| url
stringlengths 119
367
⌀ |
|---|---|---|---|---|---|---|---|---|---|
6435cb6ca41dec1a56e4f0da | 10.26434/chemrxiv-2023-tq12l | Catalytic, Sulfur-Free Chain Transfer Agents that Alter the Mechanical Properties of Crosslinked Photopolymers | Thermosetting materials generated by photopolymerization are inherently highly crosslinked and suffer from significant shrinkage stress, are often brittle, and have a limited range of mechanical properties. Various classes of chain transfer agents (CTAs) have been investigated and developed to reduce the crosslinking density of photopolymers by terminating kinetic chains and initiating new chains in situ. Although CTAs are successful in manipulating the mechanical properties of photopolymers, they are traditionally consumed during the polymerization and are therefore required in high loadings (up to 20 wt% of total formulation). Moreover, traditional CTAs frequently contain sulfur which is malodorous and can create unstable formulations. Presented here is a catalytic, sulfur-free CTA that can be added in ppm quantities to exist-ing commercial monomer feedstocks to create photopolymers similar to those prepared using traditional CTAs, but at 10,000x lower loadings. These catalysts, which are based on macrocyclic cobaloximes, were found to tunably reduce the molecular weight of the kinetic chain proportional to catalyst loading. It was shown, using only commercial monomers, that this catalyst could reduce the glass transition temperature (Tg), rubbery modulus (E’rubbery), and stiffness. | Nicholas Bagnall; Meredith Jones; G. Cole Jernigan; Chase Routt; Lisa Dar; Brady Worrell | Catalysis; Polymer Science; Organic Polymers; Materials Chemistry | CC BY NC ND 4.0 | CHEMRXIV | 2023-04-12 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/6435cb6ca41dec1a56e4f0da/original/catalytic-sulfur-free-chain-transfer-agents-that-alter-the-mechanical-properties-of-crosslinked-photopolymers.pdf |
64cd0bb3dfabaf06ffb3260d | 10.26434/chemrxiv-2023-j5hbc | Sulfamide instead urea in Biginelli reaction: from black box to reality | The scope and limitation of classical Biginelli reaction expanded to principally novel substrates: sulfamide and its monosubstituted analogues. The preparative procedure was optimized. The reasons for the unavailability of such compounds earlier were determined. The relationship between the structure and stability of final compounds and the nature of starting materials were detected. Some mechanistic observations were shown and discussed. The prospects for employing these compounds for new 3D-shape MedChem relevant libraries were disclosed. | Alexander Lyapunov; Andriy Tarnovskiy; Sergey Boron; Eduard Rusanov; Galyna Grabchuk; Dmytro Volochnyuk; Serhiy Ryabukhin | Organic Chemistry; Organic Compounds and Functional Groups; Organic Synthesis and Reactions | CC BY 4.0 | CHEMRXIV | 2023-08-07 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/64cd0bb3dfabaf06ffb3260d/original/sulfamide-instead-urea-in-biginelli-reaction-from-black-box-to-reality.pdf |
60c75484bb8c1a91cd3dc236 | 10.26434/chemrxiv.13587995.v2 | A General Pyrrolidine Synthesis via Iridium-Catalyzed Reductive Azomethine Ylide Generation from Tertiary Amides & Lactams | A new iridium-catalyzed reductive generation of both
stabilized and unstabilized azomethine ylides and their application to
functionalized pyrrolidine synthesis via [3+2] dipolar cycloaddition
reactions is described. Proceeding under mild reaction conditions
from both amide and lactam precursors possessing a suitably
positioned electron-withdrawing or a trimethylsilyl group, using
catalytic Vaska’s complex [IrCl(CO)(PPh3)2] and
tetramethyldisiloxane (TMDS) as a terminal reductant, a broad range
of (un)stabilized azomethine ylides were accessible. Subsequent,
regio- and diastereoselective, inter- and intramolecular, dipolar
cycloaddition reactions with variously substituted electron-poor
alkenes enabled ready and efficient access to structurally complex
pyrrolidine architectures. Density functional theory (DFT) calculations
of the dipolar cycloaddition reactions uncovered an intimate balance
between asynchronicity and interaction energies of transition
structures which ultimately control the unusual selectivities observed
in certain cases. | Ken Yamazaki; Pablo Gabriel; Graziano Di Carmine; Julia Pedroni; Mirxan Farizyan; Trevor Hamlin; Darren J. Dixon | Organic Synthesis and Reactions | CC BY NC ND 4.0 | CHEMRXIV | 2021-01-27 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/60c75484bb8c1a91cd3dc236/original/a-general-pyrrolidine-synthesis-via-iridium-catalyzed-reductive-azomethine-ylide-generation-from-tertiary-amides-lactams.pdf |
60c74d2dbb8c1adab43db554 | 10.26434/chemrxiv.12593825.v1 | Epimerization-free C-term Activation of Peptide Fragments by Ball-Milling | Ball-milling enabled to perform [2+1], [2+2], and [2+3] peptide couplings with high yields and, if any, very low epimerization. Very good results were obtained with peptide fragments containing highly epimerization-prone and/or highly hindered amino acids at C-term such as phenylglycine, cysteine and valine. Ball-milling was clearly identified as the key element to obtain both high yield and purity along with low epimerization. Indeed, the ball-milling conditions proved to be superior to the classical solution synthesis approach on a various array of widely used coupling agents. These results open avenues for the development of highly efficient, convergent and flexible peptide synthesis strategies based on peptide fragment couplings mediated by ball-milling. | Yves Yeboue; Marion Jean; Gilles Subra; Jean Martinez; Frédéric Lamaty; Thomas-Xavier Métro | Organic Synthesis and Reactions | CC BY NC ND 4.0 | CHEMRXIV | 2020-07-02 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/60c74d2dbb8c1adab43db554/original/epimerization-free-c-term-activation-of-peptide-fragments-by-ball-milling.pdf |
666886ec409abc03452b25c8 | 10.26434/chemrxiv-2024-vshsx | Bulk Heterojunction Organic Photoanodes for Enhanced Water Oxidation and Unassisted Solar Water Splitting | Polymer donors and non-fullerene acceptors have played an important role as photoactive materials in the development of high-efficiency organic solar cells, and they have immense potential for photoelectrochemical generation of solar fuels such as green hydrogen. However, their use in water-splitting photoelectrodes has been limited by their instability in aqueous environment and recombination losses at the interface with catalysts. Herein, PM6:D18:L8-BO organic photoanodes are presented reaching high photocurrent density over 25 mA cm-2 at +1.23 VRHE and unprecedented, days-long operational stability under solar illumination. This photoelectrochemical performance was achieved by protecting the photoactive layer by a graphite sheet functionalized with earth-abundant NiFeOOH water oxidation catalyst, providing both water resistance and electrical connection between the catalyst and the photoactive layer without any losses. This strategy also enables unassisted solar water splitting with solar-to-hydrogen efficiency of 5% by monolithic tandem organic photoanodes with PM6:D18:L8-BO and PTQ10:GS-ISO photoactive layers. These results pave the way towards high-efficiency, stable and unassisted hydrogen generation by low-cost organic photoelectrochemical cells. | Matyas Daboczi; Flurin Eisner; Joel Luke; Shi Wei Yuan; Noof Al Lawati; Jolanda Simone Müller; Ji-Seon Kim; Jenny Nelson; Salvador Eslava | Physical Chemistry; Catalysis; Energy | CC BY NC ND 4.0 | CHEMRXIV | 2024-06-12 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/666886ec409abc03452b25c8/original/bulk-heterojunction-organic-photoanodes-for-enhanced-water-oxidation-and-unassisted-solar-water-splitting.pdf |
63bf534ba68d7bcb54355068 | 10.26434/chemrxiv-2023-ls7m0 | Organic Non-Nucleophilic Electrolyte Resists Carbonation During Selective CO2 Electroreduction | The spontaneous reaction of CO2 with water and hydroxide to form (bi)carbonates in alkaline aqueous electrolytes com-promises the energy and carbon-efficiency of CO2 electrolyzers. We hypothesized that electrolyte carbonation could be mitigated in an aprotic solvent with low water content, by employing an exogenous non-nucleophilic acid capable of driving proton transfer without parasitic capture of CO2 by its conjugate base. However, it is unclear whether such an electrolyte design could engender high CO2 reduction selectivity and low electrolyte carbonation. We herein report selective CO2 electro-reduction on polycrystalline Au catalyst using dimethyl sulfoxide as the solvent and acetic acid / acetate as the proton donating medium with low carbonate formation. CO2 is reduced to CO with over 90% faradaic efficiency at potentials relative to the reversible hydrogen couple that are comparable to those in neutral aqueous electrolytes. 1H and 13C NMR studies demonstrate that only millimolar concentrations of bicarbonates are reversibly formed, that the proton activity of the medium is largely unaffected by exposure to CO2, and that low carbonation is maintained upon addition of 1 M water. This work demonstrates that electrolyte carbonation and efficient CO2 reduction can be decoupled from each other in an aprotic solvent, offering new electrolyte design principles for low-temperature CO2 electroreduction systems. | An Chu; Onyu Jung; Wei Lun Toh; Yogesh Surendranath | Catalysis; Energy; Electrocatalysis; Heterogeneous Catalysis | CC BY NC ND 4.0 | CHEMRXIV | 2023-01-12 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/63bf534ba68d7bcb54355068/original/organic-non-nucleophilic-electrolyte-resists-carbonation-during-selective-co2-electroreduction.pdf |
615c37e58b620d01f1452631 | 10.26434/chemrxiv-2021-gxjgc-v2 | Classifying Natural Products from Plants, Fungi or Bacteria using the COCONUT Database and Machine Learning | Natural products (NPs) represent one of the most important resources for discovering new drugs. Here we asked whether NP origin can be assigned from their molecular structure in a subset of 60,171 NPs in the recently reported Collection of Open Natural Products (COCONUT) database assigned to plants, fungi, or bacteria. Visualizing this subset in an interactive tree-map (TMAP) calculated using MAP4 (MinHashed atom pair fingerprint) clustered NPs according to their assigned origin (https://tm.gdb.tools/map4/coconut_tmap/), and a support vector machine (SVM) trained with MAP4 correctly assigned the origin for 94% of plant, 89% of fungal, and 89% of bacterial NPs in this subset. An online tool based on an SVM trained with the entire subset correctly assigned the origin of further NPs with similar performance (https://np-svm-map4.gdb.tools/). Origin information might be useful when searching for biosynthetic genes of NPs isolated from plants but produced by endophytic microorganisms. | Alice Capecchi; Jean-Louis Reymond | Biological and Medicinal Chemistry; Organic Chemistry; Agriculture and Food Chemistry; Natural Products; Organic Compounds and Functional Groups; Bioinformatics and Computational Biology | CC BY NC ND 4.0 | CHEMRXIV | 2021-10-05 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/615c37e58b620d01f1452631/original/classifying-natural-products-from-plants-fungi-or-bacteria-using-the-coconut-database-and-machine-learning.pdf |
60c753abbdbb895af4a3a4cb | 10.26434/chemrxiv.13318523.v2 | A Benchmark of Popular Free Energy Approaches Revealing the Inhibitors Binding to SARS-CoV2 Mpro | COVID-19 pandemic has killed millions of people
worldwide since its outbreak in Dec 2019. The pandemic is caused by the SARS-CoV-2
virus whose main protease (Mpro) is a promising drug target since it plays a
key role in viral proliferation and replication. Currently, designing an
effective therapy is an urgent task, which requires accurately estimating ligand-binding
free energy to the SARS-CoV-2 Mpro. However, it should be noted that the
accuracy of a free energy method probably depends on the protein target. A
highly accurate approach for some targets may fail to produce a reasonable
correlation with experiment when a novel enzyme is considered as a drug target.
Therefore, in this context, the ligand-binding affinity to SARS-CoV-2 Mpro was
calculated via various approaches. The Autodock Vina (Vina) and Autodock4 (AD4)
packages were manipulated to preliminary investigate the ligand-binding
affinity and pose to the SARS-CoV-2 Mpro. The binding free energy was then refined
using the fast pulling of ligand (FPL), linear interaction energy (LIE),
molecular mechanics-Poission Boltzmann surface
area (MM-PBSA), and free energy perturbation (FEP) methods. The benchmark
results indicated that for docking calculations, Vina is more accurate than AD4
and for free energy methods, FEP is the most accurate followed by LIE, FPL and
MM-PBSA (FEP > LIE ≈ FPL > MM-PBSA).
Moreover, the binding mechanism was also revealed by atomistic simulations. The
vdW interaction is the dominant factor. The residues <i>Thr26</i>, <i>His41</i>,
<i>Ser46</i>, <i>Asn142</i>, <i>Gly143</i>, <i>Cys145</i>, <i>His164</i>, <i>Glu166</i>,
and <i>Gln189</i> are essential elements affecting on the binding process. The
benchmark probably guide for further investigations using computational
approaches. | Son Tung Ngo; Nguyen Minh Tam; Pham Minh Quan; Trung Hai Nguyen | Computational Chemistry and Modeling; Chemoinformatics - Computational Chemistry | CC BY NC ND 4.0 | CHEMRXIV | 2020-12-28 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/60c753abbdbb895af4a3a4cb/original/a-benchmark-of-popular-free-energy-approaches-revealing-the-inhibitors-binding-to-sars-co-v2-mpro.pdf |
64cb8dfe69bfb8925a492e7d | 10.26434/chemrxiv-2023-g5cfx | Mesoscopic Model of Extrusion during Solvent-Free Li-Ion Battery Electrode Manufacturing | Solvent-free (SF) manufacturing of Lithium-ion battery (LIB) electrodes is safer and more environmentally friendly than the traditional slurry casting approach. However, as a young technique, SF manufacturing is under development of its pathways and operation conditions. In different SF processes reported in literature, extrusion is a common step. A detailed model of this process would be extremely computationally demanding. This work proposes a novel simplified discrete element model at the mesoscopic scale for the extrusion during SF manufacturing of LIB electrodes. In addition to active material particles, we consider fluid-like solid particles to approximate the molten polymer and the carbon additive phases. The formulation and other process parameters are taken from our experimental facility that uses extrusion to fabricate filaments for 3D printing of LIB cells. The simulations are carried out in a conical twin-screw extruder. Our approach allows to obtain representative electrode microstructures after extrusion, where electrical conductivity, ionic effective diffusivity, tortuosity factor and porosity are calculated. The model is a proof of concept that is employed to investigate the influence of the extruder speed and the cohesion level on the resulting electrode properties. | Brayan Paredes-Goyes; Franco Zanotto; Victor Boudeville; Sylvie Grugeon; Loic Dupont; Alejandro A. Franco | Theoretical and Computational Chemistry; Physical Chemistry; Energy; Computational Chemistry and Modeling; Energy Storage | CC BY 4.0 | CHEMRXIV | 2023-08-03 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/64cb8dfe69bfb8925a492e7d/original/mesoscopic-model-of-extrusion-during-solvent-free-li-ion-battery-electrode-manufacturing.pdf |
6792204c6dde43c908f90394 | 10.26434/chemrxiv-2025-szt8q-v2 | Bridging the Gap: Using Machine Learning Force Fields to Simulate Gold Break Junctions at Pulling Speeds Closer to Experiments | The properties and dynamics of gold nanowires have been studied for decades as an important testbed for several physical phenomena. Gold nanowires forming at contacts are an integral part of molecular junctions used to study the electronic and thermal properties of single molecules. However, the huge discrepancy in timescales between experiments and simulations, compounded by the limited accuracy of classical force fields, has posed a challenge in accurately simulating realistic junctions. Here we show that machine-learning force fields reveal new behaviors not captured by classical force fields when modeling Au-Au pulling junctions. Our simulations show a dependency of the average breaking distance on the pulling speed, highlighting a more complex behavior than previously thought. Our results demonstrate that the use of more accurate force fields to simulate metallic nanowires is essential to capture the complexity of their structural evolution in break junction experiments. Our developments advance the modeling accuracy of molecular junctions, bridging the gap between experimental and simulation timescales.
| William Bro-Jørgensen; Joseph M. Hamill; Davide Donadio; Gemma C. Solomon | Theoretical and Computational Chemistry; Nanoscience; Nanodevices; Computational Chemistry and Modeling; Machine Learning; Materials Chemistry | CC BY NC ND 4.0 | CHEMRXIV | 2025-01-23 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/6792204c6dde43c908f90394/original/bridging-the-gap-using-machine-learning-force-fields-to-simulate-gold-break-junctions-at-pulling-speeds-closer-to-experiments.pdf |
60c73f40bdbb891df1a37f7f | 10.26434/chemrxiv.6254756.v4 | Efficient prediction of structural and electronic properties of hybrid 2D materials using complementary DFT and machine learning approaches | <p>There are now, in principle, a limitless number of hybrid van der Waals heterostructures that can be built from the rapidly growing number of two-dimensional layers. The key question is how to explore this vast parameter space in a practical way. Computational methods can guide experimental work however, even the most efficient electronic structure methods such as density functional theory, are too time consuming to explore more than a tiny fraction of all possible hybrid 2D materials. Here we demonstrate that a combination of DFT and machine learning techniques provide a practical method for exploring this parameter space much more efficiently than by DFT or experiment. As a proof of concept we applied this methodology to predict the interlayer distance and band gap of bilayer heterostructures. Our methods quickly and accurately predicted these important properties for a large number of hybrid 2D materials. This work paves the way for rapid computational screening of the vast parameter space of van der Waals heterostructures to identify new hybrid materials with useful and interesting properties.</p> | Sherif Tawfik; Olexandr Isayev; Catherine Stampfl; Joseph Shapter; David Winkler; Michael J. Ford | Multilayers; Nanostructured Materials - Materials; Theory - Computational; Machine Learning | CC BY 4.0 | CHEMRXIV | 2018-08-20 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/60c73f40bdbb891df1a37f7f/original/efficient-prediction-of-structural-and-electronic-properties-of-hybrid-2d-materials-using-complementary-dft-and-machine-learning-approaches.pdf |
6718fde183f22e4214e92d14 | 10.26434/chemrxiv-2024-r549w | Integration of lithium-ion battery recycling into manufacturing through digitalization: A perspective | The lithium-ion batteries (LIBs) industry has expanded quickly despite technological constraints. Additionally, raw materials supply, end-of-life (EoL) management, and the creation of LIB manufacturing policies are receiving attention. All these concerns could be addressed simultaneously by integrating recycling of EoL cells from the early stages of the LIB manufacturing. This article presents perspectives on how to achieve this holistic integration through the means of digitalization. Various challenges of LIB recycling, and different digitalization tools are discussed, shedding light on the latter’s potential applications and outcomes. Through the use of the discussed tools to create advanced Digital Twins, it would be possible to screen different recycling processing conditions and materials to achieve higher efficiency, increased safety, at a lower cost. In this regard digitalization of LIB recycling process, emerges as the key for achieving a collaborative, sustainable, and efficient battery value chain in the European Union. Lastly, in the view of the growing LIB market, this article is thought to be of interest for recycling stakeholders as they move towards a more circular economy model. | Imelda Cardenas-Sierra; Utkarsh Vijay; Frederic Aguesse; Néstor Antuñano; Elixabete Ayerbe; Lukas Gold; Aleksandra Naumann; Laida Otaegui; Nadir Recham; Simon Stier; Sandro Süß; Lalitha Subramanian; Nicolas Vallin; Gabriela Ventura Silva; Nicolas Von Drachenfels; Dennis Weitze; Alejandro A. Franco | Theoretical and Computational Chemistry; Materials Science; Energy; Computational Chemistry and Modeling; Artificial Intelligence; Energy Storage | CC BY 4.0 | CHEMRXIV | 2024-10-25 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/6718fde183f22e4214e92d14/original/integration-of-lithium-ion-battery-recycling-into-manufacturing-through-digitalization-a-perspective.pdf |
60c74f2c9abda20390f8d7be | 10.26434/chemrxiv.12859559.v1 | Hypercrosslinked Polymers as a Photocatalytic Platform for Visible-Light-Driven CO2 Photoreduction Using H2O | The design of robust, high-performance photocatalysts is key for the success of solar fuel production <i>via</i> CO<sub>2</sub>conversion. Herein, we present hypercrosslinked polymer (HCP) photocatalysts for the selective reduction of CO<sub>2</sub> to CO, combining excellent CO<sub>2</sub> sorption capacities, good general stabilities, and low production costs. HCPs are active photocatalysts in the visible light range, significantly out-performing the benchmark material, TiO<sub>2</sub> P25, using only sacrificial H<sub>2</sub>O. We hypothesise that superior H<sub>2</sub>O adsorption capacities led to concentration at photoactive sites, improving photocatalytic conversion rates when compared to sacrificial H<sub>2</sub>. These polymers are an intriguing set of organic photocatalysts, displaying no long-range order or extended pi-conjugation. The as-synthesised networks are the sole photocatalytic component, requiring no co-catalyst doping or photosensitiser, representing a highly versatile and exciting platform for solar-energy conversion. | Giulia M. Schukraft; Robert Woodward; Santosh Kumar; Michael Sachs; Salvador Eslava; Camille Petit | Catalysts | CC BY NC ND 4.0 | CHEMRXIV | 2020-08-25 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/60c74f2c9abda20390f8d7be/original/hypercrosslinked-polymers-as-a-photocatalytic-platform-for-visible-light-driven-co2-photoreduction-using-h2o.pdf |
625d9436742e9f433d627299 | 10.26434/chemrxiv-2022-9p94z | An Activity-Based Oxaziridine Platform for Identifying and Developing Covalent Ligands for Functional Allosteric Methionine Sites: Redox-Dependent Inhibition of Cyclin-Dependent Kinase 4 | Activity-based protein profiling (ABPP) is a versatile strategy for enabling identification and characterization of new functional protein sites and discovery of lead compounds for therapeutic development. Yet, the vast majority of ABPP methods applied for covalent drug discovery target highly nucleophilic amino acids such as cysteine or lysine. Here, we report a methionine-directed ABPP platform using Redox-Activated Chemical Tagging (ReACT), which leverages a biomimetic oxidative ligation strategy for selective methionine modification. Application of ReACT to the cancer-driver protein cyclin-dependent kinase 4 (CDK4) as a representative high-value drug target identified three new hyperreactive, ligandable methionine residues, including an allosteric M169 site that is proximal to an activating T172 phosphorylation site. With this information in hand, we designed and synthesized a new methionine-targeting covalent ligand library based on oxaziridine fragments bearing a diverse array of heterocyclic, heteroatom, and stereochemically-rich substituents. ABPP screening of this focused library against a clickable broad-spectrum ReACT probe identified 1oxF11 as a covalent modifier of the CDK4/Cyclin-D1 heterodimer at the M169 site. This compound inhibited CDK4 kinase activity in a dose-dependent manner on purified protein and in live cells. Further biochemical analyses with a phospho-specific CDK4 antibody revealed crosstalk between M169 oxidation and T172 phosphorylation upon 1oxF11 treatment, where M169 oxidation prevented phosphorylation of the activating T172 site on CDK4 and blocked cell cycle progression at the S-phase checkpoint. By identifying a new mechanism for allosteric methionine redox regulation on CDK4 and developing a unique modality for its therapeutic intervention, this work showcases a generalizable platform that provides a starting point for engaging in broader chemoproteomics and protein ligand discovery efforts to find and target previously undruggable methionine sites. | Audrey Reeves; Angel Gonzalez-Valero; Patrick Moon; Edward Miller; Katia Coulonval; Steven Crossley; Xiao Xie; Dan He; Patricia Musacchio; Alec Christian; Jeffrey McKenna; Richard Lewis; Eric Fang; Dustin Dovala; Yipin Lu; Lynn McGregor; Markus Schirle; John Tallarico; Pierre Roger; F. Dean Toste; Christopher Chang | Biological and Medicinal Chemistry; Organic Chemistry; Organic Compounds and Functional Groups; Chemical Biology; Drug Discovery and Drug Delivery Systems | CC BY NC ND 4.0 | CHEMRXIV | 2022-04-20 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/625d9436742e9f433d627299/original/an-activity-based-oxaziridine-platform-for-identifying-and-developing-covalent-ligands-for-functional-allosteric-methionine-sites-redox-dependent-inhibition-of-cyclin-dependent-kinase-4.pdf |
60c7566bbb8c1a14f13dc60d | 10.26434/chemrxiv.14245532.v1 | Pattern Regulation of DNA Hydrogels Formed by Lateral Phase Separation of DNA Nanostructures on Water-in-Oil Droplet Interfaces | <p>Phase separation is a key phenomenon in artificial cell construction. Recent studies have shown that the liquid-liquid phase separation of designed-DNA nanostructures induces the formation of liquid-like condensates that eventually become hydrogels by lowering the solution temperature. As a compartmental capsule is an essential artificial cell structure, many studies have focused on the lateral phase separation of artificial lipid vesicles. However, controlling phase separation using a molecular design approach remains challenging. Here, we present the lateral liquid-liquid phase separation of DNA nanostructures that leads to the formation of phase-separated capsule-like hydrogels. We designed three types of DNA nanostructures (two orthogonal and a linker nanostructure) that were adsorbed onto an interface of water-in-oil droplets via electrostatic interactions. The phase separation of DNA nanostructures led to the formation of hydrogels of bicontinuous, patch, and mix patterns, due to the immiscibility of liquid-like DNA during the self-assembly process. The frequency of appearance of these patterns was regulated by designing DNA sequences and altering the mixing ratio of the nanostructures. We constructed a phase diagram for the capsule-like DNA hydrogels by investigating pattern formation under various conditions. Our results provide a method for the design and control of phase-separated hydrogel capsules using sequence-designed DNAs. We envision that by incorporating various DNA nanodevices into DNA hydrogel capsules, the capsules will gain molecular sensing, chemical-information processing, and mechano-chemical actuating functions, allowing the construction of functional molecular systems.</p> | Yusuke Sato; Masahiro Takinoue | Biopolymers; Nanostructured Materials - Nanoscience; Interfaces; Self-Assembly | CC BY NC ND 4.0 | CHEMRXIV | 2021-03-19 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/60c7566bbb8c1a14f13dc60d/original/pattern-regulation-of-dna-hydrogels-formed-by-lateral-phase-separation-of-dna-nanostructures-on-water-in-oil-droplet-interfaces.pdf |
63331c61e6150264c02895be | 10.26434/chemrxiv-2022-8jrzc | Ni-catalyzed Regioselective Reductive 1,3-Dialkenylation of Alkenes | Dicarbofunctionalization is an important efficient synthetic technique for adding two chemical moieties across an alkene. Here, a novel method of reductive dicarbofunctionalization has been developed using a single alkenyl triflate as the electrophile, combined with an unactivated alkene. The reaction does not require an external auxiliary and proceeds with complete regioselectivity. | Laura M. Wickham; Roshan K. Dhungana; Ramesh Giri | Organic Chemistry; Catalysis; Homogeneous Catalysis | CC BY NC ND 4.0 | CHEMRXIV | 2022-09-28 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/63331c61e6150264c02895be/original/ni-catalyzed-regioselective-reductive-1-3-dialkenylation-of-alkenes.pdf |
60c747a20f50db7a4c396635 | 10.26434/chemrxiv.11743788.v1 | Spin-Orbit Matrix Elements for a Combined Spin-Flip and IP/EA Approach | We present a practical approach for computing the Breit-Pauli spin-orbit matrix elements of multiconfigurational systems with both spin and spatial degeneracies based on our recently developed RAS-nSF-IP/EA method (JCTC, 15,<br />2278, 2019). The spin-orbit matrix elements over all the multiplet components are computed using a single one-particle reduced density matrix as a result of the Wigner-Eckart theorem. A mean field spin-orbit approximation was used to account for the two-electron contributions. Basis set dependence as well as the effect of including additional excitations is presented. The effect of correlating the core and semi-core orbitals is also examined. Surprisingly accurate results are obtained for spin-orbit coupling constants, despite the fact that the efficient wavefunction approximations we explore neglect the bulk of dynamical correlation.<br /> | Oinam Meitei; Shannon Houck; Nicholas Mayhall | Theory - Computational | CC BY NC ND 4.0 | CHEMRXIV | 2020-01-29 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/60c747a20f50db7a4c396635/original/spin-orbit-matrix-elements-for-a-combined-spin-flip-and-ip-ea-approach.pdf |
60c743a1469df46cfbf43220 | 10.26434/chemrxiv.9328382.v1 | Synthesis of 2H-Chromenes via Hydrazine-Catalyzed Ring-Closing Carbonyl-Olefin Metathesis | The catalytic ring-closing carbonyl-olefin
metathesis (RCCOM) of <i>O</i>-allylsalicylaldehydes
to form 2<i>H</i>-chromenes is
described. The method utilizes a
[2.2.1]-bicyclic hydrazine catalyst and operates via a [3+2]/retro-[3+2]
metathesis manifold. The nature of the allyl substitution pattern was found to
be crucial, with sterically demanding groups such as adamantylidene or
diethylidene offering optimal outcomes. A survey of substrate scope is shown
along with a discussion of mechanism supported by DFT calculations. Steric
pressure arising from syn-pentane minimization of the diethylidene moiety is
proposed to facilitate cycloreversion. | Yunfei Zhang; Janis Jermaks; Samantha N. Macmillan; Tristan Lambert | Organocatalysis | CC BY NC ND 4.0 | CHEMRXIV | 2019-08-08 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/60c743a1469df46cfbf43220/original/synthesis-of-2h-chromenes-via-hydrazine-catalyzed-ring-closing-carbonyl-olefin-metathesis.pdf |
60c74663bdbb8980e2a38be7 | 10.26434/chemrxiv.11316098.v1 | Expanding the Natural Products Heterologous Expression Repertoire in the Model Cyanobacterium Anabaena sp. Strain PCC 7120: Production of Pendolmycin and Teleocidin B-4 | Cyanobacteria are prolific producers of natural products and genome mining has shown that many orphan biosynthetic gene clusters can be found in sequenced cyanobacterial genomes. New tools and methodologies are required to investigate these biosynthetic gene clusters and here we present the use of <i>Anabaena </i>sp. strain PCC 7120 as a host for combinatorial biosynthesis of natural products using the indolactam natural products (lyngbyatoxin A, pendolmycin, and teleocidin B-4) as a test case. We were able to successfully produce all three compounds using codon optimized genes from Actinobacteria. We also introduce a new plasmid backbone based on the native <i>Anabaena</i>7120 plasmid pCC7120ζ and show that production of teleocidin B-4 can be accomplished using a two-plasmid system, which can be introduced by co-conjugation. | Patrick Videau; Kaitlyn Wells; Arun Singh; Jessie Eiting; Philip Proteau; Benjamin Philmus | Natural Products; Bioengineering and Biotechnology | CC BY NC ND 4.0 | CHEMRXIV | 2019-12-12 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/60c74663bdbb8980e2a38be7/original/expanding-the-natural-products-heterologous-expression-repertoire-in-the-model-cyanobacterium-anabaena-sp-strain-pcc-7120-production-of-pendolmycin-and-teleocidin-b-4.pdf |
60c74e4eee301cb0e0c7a4a4 | 10.26434/chemrxiv.12734039.v1 | A Computational Study of the Relative Aromaticity of Pyrrole, Furan, Thiophene and Selenophene, and Their Diels-Alder Stereoselectivity | The collinearity of terminal <i>p</i>
orbitals of a diene with that of a dienophile is required for an effective
overlap to result in s bond formation during the Diels-Alder reaction.
The ease of the DA reaction of a cyclic diene with a given dienophile,
therefore, must also depend on the distance between the termini of the diene. A
distance larger than the unsaturated bond of the dienophile is expected to
raise the energy of activation. This scenario has been amply demonstrated from
the study of reactions of several dienes, some designed to serve the purpose,
with different dienophiles. The five-ring heterocycles pyrrole, furan,
thiophene and selenophene possess varying aromatic character for the varied resonance
participation of the heteroatom lone pair with ring p bonds. The aromaticity
decreases in the same order due to: (a) the increasing s<sub>C-X</sub> (X = heteroatom) bond
length lifts the bond uniformity required for ring current, hence aromaticity, such
as in benzene and (b) size-mismatch of the interacting lone pair orbital and
the ring <i>p</i> orbitals, especially in
thiophene and selenophene, both allowing poor overlap in the ground state
structures. It is demonstrated that increase alone in the activation energies
of the DA reactions of pyrrole, furan, thiophene and selenophene cannot be considered
a measure of relative aromaticity as often done and even theoretically attempted
in many ways to prove just that. The separation of the termini of the diene has
a much larger role in the determination of activation energy, especially in
thiophene and selenophene, than their aromaticity profile. There cannot be a
measure better than the relative intensity of heteroatom lone pair overlap with
ring p bonds, giving rise to a six-electron like
system in following Hückel’s 4n+2 rule, to assess the relative aromaticity. | Veejendra Yadav | Physical Organic Chemistry; Theory - Computational | CC BY NC ND 4.0 | CHEMRXIV | 2020-07-30 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/60c74e4eee301cb0e0c7a4a4/original/a-computational-study-of-the-relative-aromaticity-of-pyrrole-furan-thiophene-and-selenophene-and-their-diels-alder-stereoselectivity.pdf |
60c740a3337d6cc6b7e26736 | 10.26434/chemrxiv.7791836.v1 | Environment-Controlled Post-Synthetic Modifications of Iron Formate Frameworks | <b>New hybrid iron-formate
perovskites have been obtained in high-pressure reactions. Apart from the
pressure range, also the liquid environment of the sample regulates the course
of transformations. Formate α-DmaFe<sup>2+</sup>Fe<sup>3+</sup>For<sub>6</sub><a>, when
compressed in oil and in isopropanol at 1.40 GPa, transforms to a new</a><a> phase<i> </i></a><i>γ</i>, different than that phase β obtained at
low-temperature. In <a></a><a></a><a></a><a></a><a></a><a>glycerol</a>
phase α can be compressed to 1.40 GPa, but then <a></a><a>reacts </a>to <a></a><a>DmaFe<sup>2+</sup>For<sub>3</sub>,
with all Fe(III) cations reduced, </a>surrounded by amorphous iron
formate <a></a><a></a><a></a><a>devoid </a>of Dma
cations. <a></a><a></a><a>Another
mixed-valence framework Dma<sub>3</sub>[Fe<sup>2+</sup><sub>3</sub>Fe<sup>3+</sup>For<sub>6</sub>]<sub>2</sub>·CO<sub>2</sub>,
can be produced from phase α incubated in methanol and ethanol at 1.15 GPa</a>. These
pressure-induced environment-sensitive modifications have been rationalised by
the volume effects involving the oxidation states of Fe(II) and
Fe(III), their high- and low-spin states as well as the properties of pressure transmitting media. The topochemical
redox reactions controlled by pressure and the liquid environment offer new
highly efficient, safe and environment-friendly reactions leading to new advanced
materials and their post-synthesise modifications.</b> | Szymon Sobczak; Andrzej Katrusiak | Hybrid Organic-Inorganic Materials; Coordination Chemistry (Organomet.); Kinetics and Mechanism - Organometallic Reactions; Physical and Chemical Properties | CC BY NC ND 4.0 | CHEMRXIV | 2019-03-04 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/60c740a3337d6cc6b7e26736/original/environment-controlled-post-synthetic-modifications-of-iron-formate-frameworks.pdf |
60c7525f567dfee90bec5c49 | 10.26434/chemrxiv.13292933.v1 | Photoinduced Regioselective Olefination of Arenes at Proximal and Distal Sites | The Fujiwara-Moritani reaction has had a profound contribution in the emergence of contemporary C−H activation protocols. Despite the applicability of the traditional approach in different fields, the associated reactivity and regioselectivity issues had rendered it redundant. The revival of this exemplary reaction requires the development of a mechanistic paradigm that would have simultaneous control on both the reactivity and regioselectivity. Often high thermal energy required to promote olefination leads to multiple site functionalization. To this aim we established a photoredox catalytic system constituting a merger of palladium/organo-photocatalyst that forges oxidative olefination in an explicit regioselective fashion of diverse arenes and heteroarenes. Visible light plays a significant role in executing ‘regio-resolved’ Fuijiwara-Moritani reaction without the requirement of silver salts and thermal energy. The catalytic system is also amenable towards proximal and distal olefination aided by respective directing groups (DGs), which entails the versatility of the protocol in engaging the entire spectrum of C(sp<sup>2</sup>)−H olefination. Furthermore, streamlining the synthesis of natural products, chiral molecules, drugs and diversification through late-stage functionalization’s underscore the importance of this sustainable protocol. The photoinduced attainment of this regioselective transformation is mechanistically established through control reactions, kinetic studies and theoretical calculations. | Argha Saha; Srimanta Guin; Wajid Ali; Trisha Bhattacharya; Sheuli Sasmal; Nupur Goswami; Gaurav Prakash; Soumya Kumar Sinha; Hediyala B. Chandrashekar; S. S. Anjana; Debabrata Maiti | Natural Products; Organic Synthesis and Reactions; Photochemistry (Org.); Stereochemistry | CC BY NC ND 4.0 | CHEMRXIV | 2020-11-27 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/60c7525f567dfee90bec5c49/original/photoinduced-regioselective-olefination-of-arenes-at-proximal-and-distal-sites.pdf |
656f22985bc9fcb5c91783a9 | 10.26434/chemrxiv-2023-hg5zc | Extending the range of distances accessible by 19F electron-nuclear double resonance in proteins using high-spin Gd(III) labels | Fluorine electron-nuclear double resonance (19F ENDOR) has recently emerged as a valuable tool in structural biology for distance determination between F atoms and a paramagnetic center, either intrinsic or conjugated to a biomolecule via spin labeling, yielding distances beyond those accessible by double electron-electron resonance (DEER). To further extend the accessible distance range we exploit the high-spin properties of Gd(III) and focus on transitions other than the central transition (|–1/2> <-> |+1/2>), that become more populated at high magnetic fields and low temperatures. This increases the spectral resolution up to ca. 7 times, thus raising the long-distance limit of ENDOR almost twofold. We first demonstrate quantitative agreement between the experimental spectra and theoretical predictions for a model fluorine containing Gd(III) complex, whose 19F spectrum is well resolved in conventional central transition measurements. We then validate our approach on two proteins labeled with 19F and Gd(III), in which the Gd-F distance is too long to produce a well resolved 19F ENDOR doublet when measured at the central transition. By focusing on the |–5/2> <-> |–3/2> and |–7/2> <-> |–5/2> EPR transitions, a resolution enhancement of 4.5 and 7 fold was obtained, respectively. We also present data analysis strategies to handle contributions of different electron spin manifolds to the ENDOR spectrum. Our new extended 19F ENDOR approach should be applicable to Gd-F distances as large as 20Å, widening the traditional ENDOR distance window. | Alexey Bogdanov; Veronica Frydman; Manas Seal; Leonid Rapatskiy; Alexander Schnegg; Wenkai Zhu; Angela M. Gronenborn; Daniella Goldfarb | Physical Chemistry; Biological and Medicinal Chemistry; Biophysical Chemistry; Spectroscopy (Physical Chem.); Structure | CC BY NC ND 4.0 | CHEMRXIV | 2023-12-06 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/656f22985bc9fcb5c91783a9/original/extending-the-range-of-distances-accessible-by-19f-electron-nuclear-double-resonance-in-proteins-using-high-spin-gd-iii-labels.pdf |
60c74f5cbdbb899c46a39d62 | 10.26434/chemrxiv.12895064.v1 | A Microscopic Description of SARS-CoV-2 Main Protease Inhibition with Michael Acceptors. Strategies for Improving Inhibitors Design | The irreversible inhibition of the main protease of SARS-CoV-2 by a Michael acceptor compound known as N3 has been investigated using multiscale simulation methods. The noncovalent enzyme-inhibitor complex was simulated using classical Molecular Dynamics techniques and the pose of the inhibitor in the active site was compared to that of the natural substrate, a peptide containing the Gln-Ser scissile bond. The formation of the covalent enzyme-inhibitor complex was then simulated using hybrid QM/MM free energy methods. After binding, the reaction mechanism was found to be composed of two steps: i) the activation of the catalytic dyad (Cys145 and His41) to form an ion pair and ii) a Michael addition where the attack of the Sg atom of Cys145 to the Cb atom of the inhibitor precedes the water-mediated proton transfer from His41 to the Ca atom. The microscopic description of protease inhibition by N3 obtained from our simulations is strongly supported by the excellent agreement between the estimated activation free energy and the value derived from kinetic experiments. Comparison with the acylation reaction of a peptide substrate suggest that that N3-based inhibitors could be improving adding chemical modifications that could facilitate the formation of the catalytic dyad ion pair. | Carlos A. Ramos-Guzmán; J. Javier Ruiz-Pernía; Iñaki Tuñón | Biochemistry; Computational Chemistry and Modeling | CC BY NC ND 4.0 | CHEMRXIV | 2020-08-31 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/60c74f5cbdbb899c46a39d62/original/a-microscopic-description-of-sars-co-v-2-main-protease-inhibition-with-michael-acceptors-strategies-for-improving-inhibitors-design.pdf |
60c741ea337d6c5dd7e2698a | 10.26434/chemrxiv.8159033.v1 | A Generic LC-MS/MS Exposome Method for the Determination of Xenoestrogens in Biological Matrices | We are constantly exposed to a variety of environmental contaminants and hormones including those mimicking endogenous estrogens. These highly heterogeneous molecules are collectively referred to as xenoestrogens and hold the potential to affect and alter the delicate hormonal balance of the human body. To monitor exposure and investigate potential health implications, comprehensive analytical methods covering all major xenoestrogen classes are urgently needed but still not available. Herein, we describe an LC-MS/MS method for the simultaneous determination of multiple classes of endogenous as well as exogenous estrogens in human urine, serum and breast milk to enable proper exposure and risk assessment. In total, 75 analytes were included, whereof a majority was successfully in-house validated in the three matrices. Extraction recoveries of validated analytes ranged from 71% to 110% and limits of quantification from 0.015 to 5 µg/L, 0.03 to 14 µg/L, and 0.03 to 4.6 µg/L in urine, serum and breast milk, respec-tively. The applicability of the novel method was demonstrated in proof of principle experiments by analyzing urine from Austrian, and breast milk from Austrian and Nigerian individuals. Thereby, we proved the methods’ feasibility to identify and quantify different classes of xenoestrogens simultaneously. The results illustrate the general importance of multi-class exposure assessment in the context of the exposome paradigm. Specifically, they highlight the need for estimating total estrogenic burden rather than single analyte or chemical class measurements and its potential impact in endocrine disruption and hormone related diseases including cancers.<br /> | Karin Preindl; Dominik Braun; Georg Aichinger; Sabina Sieri; Mingliang Fang; Doris Marko; Benedikt Warth | Analytical Chemistry - General; Environmental Analysis; Mass Spectrometry; High-throughput Screening | CC BY NC ND 4.0 | CHEMRXIV | 2019-05-23 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/60c741ea337d6c5dd7e2698a/original/a-generic-lc-ms-ms-exposome-method-for-the-determination-of-xenoestrogens-in-biological-matrices.pdf |
6772f1796dde43c908d12e21 | 10.26434/chemrxiv-2024-fpzqb-v3 | CReM-dock: de novo design of synthetically feasible compounds guided by molecular docking | De novo generation of compounds is an attractive strategy allowing to explore much broader chemical space than virtual screening. Fragment-based approaches suffer from low synthetic accessibility of generated compounds. In this study we combined the previously developed fragment-based generator CReM and molecular docking to guide the exploration of chemical space. The developed approach is very flexible and allows to indirectly control synthetic accessibility of generated compounds, their diversity by choosing one of selection strategies, augmentation of an objective function to generate more drug-like compounds, control over preserving important protein-ligand interactions and ligand poses. The generated compounds demonstrated high novelty and were competitive to compounds generated with REINVENT4. We demonstrated in different case studies flexibility of the developed approach and its applicability to de novo generation as well as fragment expansion tasks. | Guzel Minibaeva; Pavel Polishchuk | Theoretical and Computational Chemistry; Chemoinformatics - Computational Chemistry | CC BY NC 4.0 | CHEMRXIV | 2024-12-31 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/6772f1796dde43c908d12e21/original/c-re-m-dock-de-novo-design-of-synthetically-feasible-compounds-guided-by-molecular-docking.pdf |
662c28ca91aefa6ce18972af | 10.26434/chemrxiv-2024-n01cs-v2 | Multi-Scale Modeling of Physical Properties of Nanoporous Frameworks: Predicting Mechanical, Thermal and Adsorption Behavior | Nanoporous frameworks are a large and diverse family of materials, with a key role in various industrial processes and applications such as energy production and conversion, fluid separation, gas storage, water harvesting, and many more. The performance and suitability of nanoporous materials for each specific application are directly related to both its physical and chemical properties, and their determination is crucial for process engineering and optimization of performances. In this Account, we focus on some recent developments in the multi-scale modeling of physical properties of nanoporous frameworks, highlighting the latest advances in three specific areas: mechanical properties, thermal properties, and adsorption. For the study of the mechanical behavior of nanoporous materials, the last few years have seen a rapid acceleration of research. For example, computational resources have been pooled to created public large-scale databases of elastic constants: those can serve as a basis for data-based discovery of materials with targeted properties, as well as the training of machine learning predictor models. The large-scale prediction of thermal behavior, in comparison, is not yet routinely performed at such large scale. Tentative databases have been assembled at the DFT level on specific families of materials, like zeolites, but prediction at larger scale currently requires the use of transferable, classical force fields, whose accuracy can be limited. Finally, adsorption is naturally one of the most studied physical properties of nanoporous frameworks, as fluid separation or storage is often the primary target for these materials. We highlight the recent achievements and open challenges for adsorption prediction at large scale, focusing in particular on the accuracy of computational models and the reliability of comparisons with experimental data available. We detail some recent methodological improvements in the prediction of adsorption-related properties, including thermodynamic quantities and transport properties. Finally, we stress the importance for data-based methods of addressing all sources of uncertainty. The Account concludes with some perspectives about the latest developments and open questions in data-based approaches, and the integration of computational and experimental data together in the materials discovery loop. | Arthur Hardiagon; François-Xavier Coudert | Theoretical and Computational Chemistry; Materials Science | CC BY 4.0 | CHEMRXIV | 2024-04-29 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/662c28ca91aefa6ce18972af/original/multi-scale-modeling-of-physical-properties-of-nanoporous-frameworks-predicting-mechanical-thermal-and-adsorption-behavior.pdf |
621dbaee57a9d274ff6ef244 | 10.26434/chemrxiv-2021-l2zd5-v3 | Identifying signatures of proteolytic
stability and monomeric propensity in
O-glycosylated insulin using molecular
simulation | Insulin has been commonly adopted as a peptide drug to treat diabetes given its ability to facilitate
the uptake of glucose from the blood. The development of oral insulin remains elusive over decades
owing to its susceptibility to the enzymes in the gastrointestinal tract and poor permeability through the
intestinal epithelium upon dimerization. Recent experimental studies have revealed that certain O-linked
glycosylation patterns could enhance insulin’s proteolytic stability and reduce its dimerization propensity,
but the understanding of such phenomena at the molecular level is still evasive. To address this challenge,
we propose and test several structural determinants that could potentially in uence insulin’s proteolytic stability
and dimerization propensity. We used these as the metrics to assess the properties of interest from
10 s aggregate molecular dynamics of each of 12 targeted insulin glyco-variants from multiple wild-type
crystal structures. We found that glycan-involved hydrogen bonds and glycan-dimer occlusion were useful
metrics predicting the proteolytic stability and dimerization propensity of insulin, as was in part the solvent
accessible surface area of proteolytic sites, while other plausible metrics were not generally predictive. This
work helps better explain how O-linked glycosylation in uences the proteolytic stability and monomeric
propensity of insulin, illuminating a path towards rational molecular design of insulin glycoforms. | Wei-Tse Hsu; Dominique Ramirez; Tarek Sammakia; Zhongping Tan; Michael Shirts | Theoretical and Computational Chemistry; Computational Chemistry and Modeling | CC BY 4.0 | CHEMRXIV | 2022-03-02 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/621dbaee57a9d274ff6ef244/original/identifying-signatures-of-proteolytic-stability-and-monomeric-propensity-in-o-glycosylated-insulin-using-molecular-simulation.pdf |
60c748704c89190550ad2f16 | 10.26434/chemrxiv.11907750.v1 | Fast Recovery of Lead from Hydrochloric Acid via a Novel Silica-Supported Anion Exchange Resin for the Determination of 210Pb in Environmental Samples | The<b> </b>measurement of <sup>210</sup>Pb is
significant in environmental studies. Lead separation in HCl solution is a
vital procedure but suffers from poor efficiency with high labor and time
costs. To overcome this problem, a novel anion exchange resin was synthesized
and characterized by different techniques followed by studies on the adsorption
behaviors towards lead in HCl solution. The results suggest that SiPS-N(CH<sub>3</sub>)<sub>3</sub>Cl
was successfully prepared with small particle size, low water swelling rate,
and large specific surface area. The maximum anion exchange capacity resulted
from quaternary amine groups was determined to be 1.0 mmol (Cl<sup>-</sup>)/g.The
adsorption activities reached equilibrium within 3 min under selected
conditions offering extremely fast adsorption kinetics. The synergistic
adsorption mechanism, the multilayer adsorption mechanism, and the competition
from co-existing chloride anions were found to be responsible for the lead
adsorption performance of SiPS-N(CH<sub>3</sub>)<sub>3</sub>Cl. Column experiments
showed that the feeding volume of lead and HCl had impact on the chemical yield
regardless of the co-existence of high concentrations of FeCl<sub>3</sub> (90
mM) and a high flow speed (4.0 mL/min). Based on these results, a separation
process integrating SiPS-N(CH<sub>3</sub>)<sub>3</sub>Cl and the matched
parameters was finally developed and tested. Our work greatly raised the lead
separation efficiency in HCl solutions with implications for measuring <sup>210</sup>Pb
in environmental samples. | Lifeng Chen; Jie Zhang; Xianwen He; Manqing Liu; Qiuyang Wei; Xinpeng Wang; Yuezhou Wei | Organic Polymers; Analytical Chemistry - General; Environmental Analysis; Separation Science; Process Control | CC BY NC ND 4.0 | CHEMRXIV | 2020-02-28 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/60c748704c89190550ad2f16/original/fast-recovery-of-lead-from-hydrochloric-acid-via-a-novel-silica-supported-anion-exchange-resin-for-the-determination-of-210pb-in-environmental-samples.pdf |
65782db2fd283d7904d288ba | 10.26434/chemrxiv-2023-177pg-v2 | Structural Coarse-Graining via Multi-Objective Optimization with Differentiable Simulation | In the realm of multiscale molecular simulations, structure-based coarse graining is a prominent approach for creating efficient coarse-grained (CG) representations of soft matter systems such as polymers. This involves optimizing CG interactions by matching static correlation functions of corresponding degrees of freedom in all-atom (AA) models. Here, we present a versatile method, namely, differentiable coarse-graining (DiffCG), which combines multi-objective optimization and differentiable simulation. The DiffCG approach is capable of constructing robust CG models by iteratively optimizing effective potentials to simultaneously match multiple target properties. We demonstrate our approach by concurrently optimizing bonded and non-bonded potentials of a CG model of polystyrene (PS) melts. The resulting CG-PS model accurately reproduces both structural and thermodynamic properties of the AA counterpart. More importantly, leveraging the multi-objective optimization capability, we develop a precise and efficient CG model for PS melts that is transferable across a wide range of temperatures, i.e., from $400$ to $600$ K. It is achieved via optimizing a pairwise potential with nonlinear temperature dependence in the CG model to simultaneously match target data from AA-MD simulations at multiple thermodynamic states. Our work showcases a promising route for developing accurate and transferable CG models of complex soft-matter systems through multi-objective optimization with differentiable simulation. | Zhenghao Wu; Tianhang Zhou | Theoretical and Computational Chemistry; Polymer Science; Polymer chains; Computational Chemistry and Modeling; Machine Learning | CC BY 4.0 | CHEMRXIV | 2023-12-12 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/65782db2fd283d7904d288ba/original/structural-coarse-graining-via-multi-objective-optimization-with-differentiable-simulation.pdf |
64f53f8fdd1a73847f20eb2a | 10.26434/chemrxiv-2023-0hnvj | Unveiling the Energy Storage Mechanism of MXenes under the Acidic Condition through Transitions of Surface Functionalizations | The high capacitive performance of MXenes in acidic electrolytes have made them potential electrode materials for supercapacitors. In this study, we conducted a structural analysis of MXene surface functionalizations by identifying the surface group distribution pattern and revealed the energy storage process of MXene surface chemistry by combining a complete Pourbaix stability diagram and density functional theory (DFT) calculations. The Pourbaix diagram indicated that pH controls the surface termination; an acidic pH generates favorable initial surfaces of MXenes with a specific distribution of functional groups (ten hydroxyls with respect to eighteen total locations for the selected surface unit). Using this, we report the charging and uncharging process of MXenes with transitions of surface oxygenic groups (-OH and -O) via hydrogen ion adsorptions and desorptions on the MXene surface. Our results demonstrated that transitions of surface functionalizations contribute to comparable pseudocapacitance and electrostatic capacitance for MXenes. These findings provide insights into understanding the MXene energy storage mechanism by controlling surface functionalizations through the experimental reaction environment and synthesis condition. | Zheng Bo; Yucheng Chen; Qian Yu; Jianhua Yan; Kefa Cen; Zhu Liu | Theoretical and Computational Chemistry; Energy; Materials Chemistry | CC BY NC ND 4.0 | CHEMRXIV | 2023-10-11 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/64f53f8fdd1a73847f20eb2a/original/unveiling-the-energy-storage-mechanism-of-m-xenes-under-the-acidic-condition-through-transitions-of-surface-functionalizations.pdf |
656619ddcf8b3c3cd7559081 | 10.26434/chemrxiv-2023-cw4bz | Straightforward Synthesis of Molsidomine and Mesocarb Analogue via Mechanochemical Desymmetrization of CDI | The mechanosynthesis of N6-functionalized iminosydnones was performed via a convergent strategy based on the desymmetrization of CDI. The whole process was carried out by ball-milling, offering an efficient and sustainable access to bioactive iminosydnones. | Nicolas Petry; Xavier Bantreil; Frédéric Lamaty | Organic Chemistry; Organic Compounds and Functional Groups; Organic Synthesis and Reactions | CC BY NC ND 4.0 | CHEMRXIV | 2023-11-29 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/656619ddcf8b3c3cd7559081/original/straightforward-synthesis-of-molsidomine-and-mesocarb-analogue-via-mechanochemical-desymmetrization-of-cdi.pdf |
6176d0c8ff3ba96da7a24cac | 10.26434/chemrxiv-2021-4h434 | Expedient Synthesis of Bis(imidazolium) Dichloride Salts and Bis(NHC) Complexes from Imidazoles using DMSO as a Key Polar Additive | A general approach for the synthesis of bis(imidazolium) dichloride salts from imidazoles and dichloroalkanes is reported. Typical limitations of this reaction for the formation of methylene-bridged derivatives are addressed herein through the use of an excess CH2Cl2 in the presence of DMSO as a polar cosolvent, significantly improving conversion rates presumably via stabilization of the initial SN2 transition state. The method was also shown to be applicable to the formation of bis(pyridinium) dichloride salts from pyridine derivatives, and to the direct synthesis of metal-bis(NHC) complexes from imidazoles. | Kyle Penn; Evan Anders; Vincent Lindsay | Organic Chemistry; Organometallic Chemistry; Organic Synthesis and Reactions; Catalysis | CC BY NC ND 4.0 | CHEMRXIV | 2021-10-28 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/6176d0c8ff3ba96da7a24cac/original/expedient-synthesis-of-bis-imidazolium-dichloride-salts-and-bis-nhc-complexes-from-imidazoles-using-dmso-as-a-key-polar-additive.pdf |
60c75240702a9b757918c0cd | 10.26434/chemrxiv.13275005.v1 | Chromium Reduction via a Semi-Conducting Hematite Electrode: Implications for Microbial Cycling of Metals in Natural Soils | Semi-conducting Fe oxide minerals, such as hematite, are well known to influence the
fate of contaminants and nutrients in many environmental settings and influence microbial
growth under suboxic to anoxic conditions through a myriad of different processes. Recent
studies of Fe oxide reduction by Fe(II) have demonstrated that reduction of Fe at one surface can result in the release of Fe(II) different one. Termed Fe(II) catalyzed recrystallization, this
phenomena is attributed to conduction of additional electrons through the mineral structure from
the point of contact to another which occurs because of the minerals’ semi-conductivity. While it
is well understood that Fe(II) plays a central role in redox cycling of elements, the environmental
implications of Fe(II) catalyzed recrystallization need to be further explored. Here, we provide
evidence that the Fe mineral conductivity underpinning Fe(II) catalyzed recrystallization can
couple the reduction of Cr, a priority metal contaminant, with an electron source that is cannot
directly affect Cr. This is shown for both an abiotic electron source, a potentiostat, as well as the
metal reducing bacteria Shewanella Putrefaciens. The implications of this work show that semiconductive minerals may be links in subsurface electrical networks that physically distribute
redox chemistry and suggests novel methods for remediating Cr contamination in groundwater. | Michael Chen; Neha Mehta; Benjamin D. Kocar | Geochemistry | CC BY NC ND 4.0 | CHEMRXIV | 2020-11-24 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/60c75240702a9b757918c0cd/original/chromium-reduction-via-a-semi-conducting-hematite-electrode-implications-for-microbial-cycling-of-metals-in-natural-soils.pdf |
660ed74721291e5d1d11c7e2 | 10.26434/chemrxiv-2024-j1jwp | Homonuclear Simplified Preservation of Equivalent Pathways Spectroscopy | Recently developed homonuclear Transverse mixing Optimal control Pulses (hTROP) revealed an elegant way to enhance the detected signal in multi-dimensional magic-angle spinning (MAS) NMR experiments. Inspired by their work, we present two homonuclear simplified preservation of equivalent pathways spectroscopy (hSPEPS) sequences for recoupling CA-CO and CA-CB dipolar couplings under fast and ultra-fast MAS rates, theoretically enabling a √2 improvement in sensitivity for each indirect dimension. The efficiencies of hSPEPS is evaluated for non-deuterated samples of influenza A M2 and bacterial rhomboid protease GlpG under two different external magnetic fields (600 MHz and 1200 MHz) and MAS rates (55 kHz and 100 kHz). 3D (H)CA(CO)NH, 3D (H)CO(CA)NH and 3D (H)CB(CA)NH spectra demonstrate the high robustness of hSPEPS elements to excite carbon-carbon correlations, especially in the (H)CB(CA)NH spectrum, where hSPEPS outperforms the J-based sequence by a factor of, on average, 2.85. | Evgeny Nimerovsky; Spyridon Kosteletos; Sascha Lange; Stefan Becker; Adam Lange; Loren B. Andreas | Physical Chemistry | CC BY NC 4.0 | CHEMRXIV | 2024-04-05 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/660ed74721291e5d1d11c7e2/original/homonuclear-simplified-preservation-of-equivalent-pathways-spectroscopy.pdf |
67ab3f2c6dde43c90863b6b3 | 10.26434/chemrxiv-2025-3484j | Metaverse For Battery Manufacturing: Connecting Students From Different Geographical Locations To Solve Battery Manufacturing Problems In The Virtual Reality Space | Laboratory practices are essential to prepare students and professionals to drive future innovations in the field of energy storage and conversion. However, universities and industries working in the battery field encounter challenges such as effective and efficient training on complex concepts related to battery production, mostly due to the lack of access to battery prototyping facilities or the limited availability of battery manufacturing pilot lines for training purposes. This Concept introduces an innovative educational platform in Virtual Reality (VR) named Battery Manufacturing Metaverse (BMM). BMM promotes accessibility, inclusion and collaborative learning of Lithium Ion Battery (LIB) manufacturing through an interactive and flexible VR representation of a LIB manufacturing pilot line. It enables collaboration among students and researchers from different geographical locations. Users can explore electrode and cell chemistries and adjust manufacturing parameters with informative feedback from a cell’s composition to the functioning of the manufacturing equipment. BMM does it with real-time collaboration using avatars and voice chat. This platform aims to connect universities of i-MESC (Interdisciplinarity in Materials for Energy Storage and Conversion, previously MESC+), an Erasmus+ MSc. Program, enabling seamless knowledge sharing and training. BMM represents a transformative step in battery research and education, offering an immersive, interactive environment without geographical barriers to pave the way towards global education and safe training in the energy sector. | Soorya Saravanan; Utkarsh Vijay; Sophie Tran; Maris Minna Mathew; Desislava Yordanova Apostolova; Inaki Gandarias; Aubin Leclere; Romain Lelong; Alejandro A. Franco | Energy; Energy Storage | CC BY 4.0 | CHEMRXIV | 2025-02-13 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/67ab3f2c6dde43c90863b6b3/original/metaverse-for-battery-manufacturing-connecting-students-from-different-geographical-locations-to-solve-battery-manufacturing-problems-in-the-virtual-reality-space.pdf |
64994fb34821a835f369acb7 | 10.26434/chemrxiv-2023-2m263 | Small molecule ligands of the BET-like bromodomain, SmBRD3, affect Schistosoma mansoni survival, oviposition, and development | Schistosomiasis is a disease affecting over 200 million people worldwide, but its treatment relies on a single agent, praziquantel. To investigate new avenues for schistosomiasis control, we have conducted the first systematic analysis of bromodomain-containing proteins (BCPs) in a causative species, Schistosoma mansoni. Having identified 29 putative bromodomains (BRDs) in 22 S. mansoni proteins, we selected SmBRD3, a tandem BRD-containing BCP that shows high similarity to the human bromodomain and extra terminal domain (BET) family, for further studies. Screening of 697 small molecules identified the human BET BRD inhibitor I-BET726 as a ligand for SmBRD3. An X-ray crystal structure of I-BET726 bound to the second BRD of SmBRD3 [SmBRD3(2)] enabled rationale design of a quinoline-based ligand (15) with an ITC Kd value of 364 ± 26.3 nM for SmBRD3(2). The ethyl ester pro-drug of compound 15 (compound 22) shows substantial effects on sexually immature larval schistosomula, sexually mature adult worms, and snail-infective miracidia in ex vivo assays. This compound will form the basis for future studies into new treatments for schistosomiasis. | Matthias Schiedel; Darius McArdle; Gilda Padalino; Anthony Chan; Josephine Forde-Thomas; Michael McDonough; Helen Whiteland; Manfred Beckmann; Rosa Cookson; Karl Hoffmann; Stuart Conway | Biological and Medicinal Chemistry; Chemical Biology; Drug Discovery and Drug Delivery Systems | CC BY 4.0 | CHEMRXIV | 2023-06-26 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/64994fb34821a835f369acb7/original/small-molecule-ligands-of-the-bet-like-bromodomain-sm-brd3-affect-schistosoma-mansoni-survival-oviposition-and-development.pdf |
65f97181e9ebbb4db90546ce | 10.26434/chemrxiv-2024-t9dqq | Access to Spiro-bicyclo[2.1.1]hexanes via BF3∙Et2O-Catalyzed Formal [2π + 2σ] Cycloaddition of Bicyclo[1.1.0]butanes with Benzofuran-derived Oxa(aza)dienes | Herein, we have developed a method for the construction of spiro[benzofuran-2,2'-bicyclo[2.1.1]hexanes] via BF3·Et2O-catalyzed formal [2π + 2σ] cycloaddition of bicyclo[1.1.0]butanes with benzofuran-derived oxa(aza)dienes. This transformation allowed for facile access to a variety of functionalized spiro-bicyclo[2.1.1]hexanes in good yields (up to 99% yield) with excellent regioselectivities and a broad substrate scope (34 examples) under mild reaction conditions. Moreover, the synthetic utility of the cycloadducts were further emphasized through a scale-up experiment and subsequent synthetic transformations. | Jia-Yi Su; Jian Zhang; Zhi-Yun Xin; Hanliang Zheng; Hao Li; Wei-Ping Deng | Organic Chemistry; Organic Synthesis and Reactions | CC BY 4.0 | CHEMRXIV | 2024-03-21 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/65f97181e9ebbb4db90546ce/original/access-to-spiro-bicyclo-2-1-1-hexanes-via-bf3-et2o-catalyzed-formal-2-2-cycloaddition-of-bicyclo-1-1-0-butanes-with-benzofuran-derived-oxa-aza-dienes.pdf |
67bc04e8fa469535b9a6b21a | 10.26434/chemrxiv-2024-h0b3g-v2 | Single Semiconductor-Based Photocurrent Switching via Light Intensity for Selective Biosensing | The mechanism behind photocurrent generation is essential for tuning photoelectrochemical properties of semiconductors and fabricating related devices. As a basic parameter, the photocurrent polarity has been exploited for information processing and can be regulated by constructing suitable interfaces/junctions of semiconductors, tuning external bias potential, or light wavelengths. Nonetheless, light intensity is generally thought to affect only the photocurrent intensity rather than the photocurrent polarity. Here, we report a universal strategy to modulate the photocurrent polarity of a single semiconductor-based photoelectrode by light intensity. Photoelectrochemical kinetic measurements revealed that the surface states, bias potential, and light intensity jointly played crucial roles in the process of photogenerated carrier transfer, thus determining the photocurrent polarity. Based on the different charge transfer pathways produced simply under light of different intensities, a highly selective PEC sensing platform was demonstrated for dopamine detection without any sophisticated biorecognition processes. | Wang Li; Hong Yang; Qiushi Ruan; Sicheng Liang; Yanfei Shen; Songqin Liu; Haibin Zhu; Yuanjian Zhang | Physical Chemistry; Analytical Chemistry; Electrochemical Analysis; Electrochemistry - Mechanisms, Theory & Study | CC BY NC ND 4.0 | CHEMRXIV | 2025-02-25 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/67bc04e8fa469535b9a6b21a/original/single-semiconductor-based-photocurrent-switching-via-light-intensity-for-selective-biosensing.pdf |
66b2df98c9c6a5c07a3c4306 | 10.26434/chemrxiv-2024-w9z02 | Chemical and Optoelectronic Control of Ti3C2Tx MXene Work Function Values via Covalently-Tethered Electron Withdrawing or Electron Donating Organic Monolayers | We functionalized Ti3C2Tx MXene surfaces with organosilanes to modify the interfacial electronic configuration and work function values. Modifications included reaction with trimethoxy(3,3,3-trifluoropropyl)silane to yield a terminal electron-withdrawing group. Modification to yield a terminal electron donating character relative to nonderivatized MXene utilized (3-aminopropyl)trimethoxysilane (APTMS). X-ray photoelectron spectroscopy (XPS) established successful derivatization of Ti3C2Tx MXene surfaces with each silane in a process that did not deleteriously oxidize the MXene material. Ultraviolet photoelectron spectroscopy (UPS) quantified work-function values for resulting derivatized Ti3C2Tx thin films. Ultraviolet photoelectron spectroscopy (UPS) established shifts in work function values of ~350–400 meV relative to nonderivatized Ti3C2Tx MXenes based on interfacial dipoles resulting from covalent organosilane attachment. We discuss these results in the context of EMI shielding, catalysis, chemical sensing, and energy applications. | Julia Martin; Olivia Dube; Rebecca Ramthun; Kiana Montazeri; Mary Qin Hassig; Daniel Harris; Ken Ngo; Varun Natu; Lyubov Titova; Joshua Uzarski; Michel Barsoum; Ronald Grimm | Physical Chemistry; Nanoscience; Interfaces; Spectroscopy (Physical Chem.); Surface; Materials Chemistry | CC BY NC ND 4.0 | CHEMRXIV | 2024-08-08 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/66b2df98c9c6a5c07a3c4306/original/chemical-and-optoelectronic-control-of-ti3c2tx-m-xene-work-function-values-via-covalently-tethered-electron-withdrawing-or-electron-donating-organic-monolayers.pdf |
61b73e2602d90de6b861119b | 10.26434/chemrxiv-2021-zwz4f | Achieving High Performance Molecular
Rectification through Fast Screening Alkanethiol
Carboxylate-Metal Complexes Electro-Active
Unites | Achieving high rectifying performance of molecular scale diode devices through synthetic chemistry and device construction remain a formidable challenge due to the complexity of the charge transport process and the device structure. We demonstrated here high-performance molecular rectification realized in self-assembled monolayer (SAM) based device by low-cost and fast screening the electroactive units. SAMs of commercial available carboxylate terminated alkane thiols on gold substrate, coordinated with a variety of metal ions, structures denoting as Au-S-(CH2)n-1COO-Mm+ (Cn+Mm+), where n=11, 12, 13, 14, 16, 18 and Mm+=Ca2+, Mn2+, Fe2+,
Fe3+, Co2+, Ni2+, Cu2+, Zn2+, were prepared and junctions were measured using a eutectic indiumgallium alloy top contact (EGaIn). The C18+Ca2+ and C18+Zn2+ junctions were found to afford a record high rectification ratio (RR) of 756 at ±1.5 V. Theoretical analysis based on single level
tunneling model shows that optimized combination of the asymmetry voltage division, energy barrier and the coupling of carboxylate-metal complex with electrode. Our method described here represent a general strategy for fast, cheap and effective exploration of the metal complex chemical space for high-performance molecular diodes devices. | Lixain Tian; Aiqing Fan; Xi Yu; Wenping Hu | Physical Chemistry; Self-Assembly; Transport phenomena (Physical Chem.) | CC BY NC ND 4.0 | CHEMRXIV | 2021-12-28 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/61b73e2602d90de6b861119b/original/achieving-high-performance-molecular-rectification-through-fast-screening-alkanethiol-carboxylate-metal-complexes-electro-active-unites.pdf |
63d7f985d8f55fd0aa94fa36 | 10.26434/chemrxiv-2023-kpmj5 | Target-directed dynamic combinatorial chemistry affords inhibitors of Nsp10 as potential antivirals against SARS-CoV-2 | The development of antiviral drugs against the Severe Acute Respiratory Syndrome coronavirus 2 (SARS-CoV-2) responsible for the recent worldwide Covid-19 pandemic is important, as treatment options are still very limited and vaccination largely does not prevent infection. Two underexplored potential targets of this virus are the 3to5 exoribonuclease (ExoN) and the 2-O-methyltransferase (2-O-Mtase), which are essential for the viability of the virus. The non-structural protein Nsp14 displays the first enzymatic activity, and Nsp16 the latter, especially while in complex with their co-factor protein Nsp10. Herein, we report the use of target-directed dynamic combinatorial chemistry to find binders of Nsp10, in the aim of preventing the formation of the Nsp10-Nsp14 and Nsp10-Nsp16 protein-protein interaction (PPI). We synthesised the hits, and tested them for their affinity Nsp10 affinity, their inhibition of ExoN and 2-O-methyltransferase activities, as well as their anti-viral potential in a hCoV-229E and SARS-CoV-2 whole-cell setting. We report a novel class of inhibitors of ExoN and/or 2-O-methyltransferase activities that present an anti-viral activity against coronaviruses. | Ravindra P. Jumde; Gwenaëlle Jézéquel; Margarida Saramago; Nicolas Frank; Sebastian Adam; Marta V. Cunha; Chantal Bader; Antonia P. Gunesch; Natalie M. Köhler; Sandra Johannsen; Thomas Pietschmann; Rute G. Matos; Rolf Müller; Cecilia M. Arraiano; Anna K. H. Hirsch | Biological and Medicinal Chemistry; Drug Discovery and Drug Delivery Systems | CC BY NC ND 4.0 | CHEMRXIV | 2023-01-31 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/63d7f985d8f55fd0aa94fa36/original/target-directed-dynamic-combinatorial-chemistry-affords-inhibitors-of-nsp10-as-potential-antivirals-against-sars-co-v-2.pdf |
60c742899abda2aad2f8c02d | 10.26434/chemrxiv.8306414.v1 | Decomposition Kinetics of Perfluorinated Sulfonic Acids | A theoretical study of the decomposition kinetics of PFOS and other perfluorinated sulfonic acids, using density functional theory, wavefunction theory, and statistical reaction rate theory techniques.<br /> | Muhammad Yasir Khan; SUI SO; Gabriel da Silva | Physical Organic Chemistry; Atmospheric Chemistry; Environmental Science; Computational Chemistry and Modeling; Chemical Kinetics | CC BY NC ND 4.0 | CHEMRXIV | 1970-01-01 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/60c742899abda2aad2f8c02d/original/decomposition-kinetics-of-perfluorinated-sulfonic-acids.pdf |
64a8fc429ea64cc167a57d19 | 10.26434/chemrxiv-2023-3gcmq | Laser Spectroscopic Characterization of Supersonic Jet Cooled 2,7-Diazaindole (27DAI) | This article presents an extensively curated rich set of gas phase spectroscopic data of 2,7-diazaindole in the ground and excited states. Single vibronic level fluorescence spectroscopy (SVLF) was performed to determine the ground state vibrations of the molecule, which depicted a large Franck-Condon activity of the bands beyond 2600 cm-1. For the excited state, laser-induced fluorescence (LIF) and resonant two-colour two-photon ionization spectroscopy (R2PI) were performed. The band origin 〖(0〗_0^0) for S1←S0 transition appeared at 33910±1 cm-1 . The Frank-Condon active vibrational modes in the spectra were seen till 〖(0〗_0^0)+ 1600 cm-1 region, which suggested the similar ground and excited state geometries. The lower energy asymmetric vibrational modes at 207, 252 and 358 cm-1, observed in the excited state were absent in the SVLF spectrum. IR-UV double Hole Burning spectroscopy confirmed the absence of any other isomeric species in the molecular beam. Ionization potential (I.P) of the molecule was found to be 8.9310.001 eV, recorded using photoionization efficiency spectroscopy. The above value is significantly higher than the related azaindole derivatives. The ground and excited state N-H stretching frequencies of the molecule were determined using fluorescence-dip infrared spectra (FDIR) and resonant ion-dip infrared spectroscopy (IDIR), obtained at 3523 and 3467 cm-1, respectively. The lower value of NH in the electronic excited state implies the higher acidity of the group compared to the ground state. Moreover, to understand the excited state properties of the molecule, a comparative analysis of the experimental LIF/2C-R2PI spectra was done against Franck-Condon simulated spectra at three different levels of theories. The vibrational frequencies calculated at B3LYP-D4/def2-TZVPP showed the most accurate prediction on comparison with the experimentally detected symmetric modes in the ground state. However, in the excited state, the low energy asymmetric modes were correctly determined at B3LYP/def-SVP level of theory. This is most probably due to the distortion observed at the pyrazolyl ring leading to the appearance of asymmetric vibrational modes. However, all the three methods have shown nearly similar correlation with the experimental frequencies in the excited state, which was evident from their similar scaling factors. | Simran Baweja; Bhavika Kalal; surajit Maity | Physical Chemistry; Spectroscopy (Physical Chem.) | CC BY NC ND 4.0 | CHEMRXIV | 2023-07-10 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/64a8fc429ea64cc167a57d19/original/laser-spectroscopic-characterization-of-supersonic-jet-cooled-2-7-diazaindole-27dai.pdf |
66a24be401103d79c5a75e71 | 10.26434/chemrxiv-2024-6b2nh | Active Redox-Driven Photoselective Self-Organization | Self-organization is a key pathway to achieving high levels of matter complexity. However, an energy-consuming active process, such as a dissipative regime, is essential for adaptation and evolution to occur. In this study, we transform the passive self-organization of a luminescent square planar Pt(II) complex into an active process through the photo or chemical reduction of the corresponding octahedral Pt(IV) complex. This transformation enables the formation of metastable supramolecular fibers, which are inaccessible via conventional methods. The fibers obtained, featuring Pt∙∙∙Pt metallophilic interactions, gain new photophysical properties compared to the monomer, including the ability to absorb visible light up to 550 nm. This enhanced capability allows for selective elongation of fibers, as low-energy irradiation enables the aggregates to convert Pt(IV) to Pt(II) and grow, while preventing the formation of new nuclei. | ALESSANDRO ALIPRANDI; Dario Alessi; Luca Morgan; Elisa Pelorosso; Claudia Graiff | Organometallic Chemistry; Transition Metal Complexes (Organomet.) | CC BY 4.0 | CHEMRXIV | 2024-07-26 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/66a24be401103d79c5a75e71/original/active-redox-driven-photoselective-self-organization.pdf |
64527fb607c3f02937273f2d | 10.26434/chemrxiv-2023-tmlt3 | Gold Nanoparticle Translocation Across a Droplet Interface Bilayer via Dark-Field Microscopy | For a wide range of biomedical applications, measuring the transport of metal nanoparticles across a cell membrane is of tremendous interest. Such studies are gaining high importance due to applications, especially in the field of drug delivery using NPs. In this work, we measure the passive transport of arginine-functionalized ultra-small gold nanoparticles (AuNPs) with sizes lower than 3 nm across a planar lipid bilayer formed with the droplet interface bilayer (DiB) technique. The AuNPs transport is monitored using dark-field microscopy, which enables the tracking of AuNPs without the use of fluorescent labeling. The measurements of high numbers of events provide a robust quantitative estimation of AuNP translocation dynamics and energy barrier obtained from the lipid bilayer translocation analysis. Interestingly, we observed that the arginine number coated onto AuNP and the bilayer packing control the AuNPs translocation accross the lipid bilayer. | jean baptiste fleury; sean moro; virginie faure; xavier le guevel | Physical Chemistry; Analytical Chemistry; Nanoscience; Analytical Chemistry - General; Physical and Chemical Processes; Transport phenomena (Physical Chem.) | CC BY NC ND 4.0 | CHEMRXIV | 2023-05-04 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/64527fb607c3f02937273f2d/original/gold-nanoparticle-translocation-across-a-droplet-interface-bilayer-via-dark-field-microscopy.pdf |
60c746890f50db5f8339647d | 10.26434/chemrxiv.11294480.v1 | ChemEnv : A Fast and Robust Coordination Environment Identification Tool | Coordination or local environments have been used to describe, analyze, and understand crystal structures for more than a century. Here, we present a new tool called <i>ChemEnv</i>, which can identify coordination environments in a fast and robust manner. In contrast to previous tools, the assessment of the coordination environments is not biased by small distortions of the crystal structure. Its robust and fast implementation enables the analysis of large databases of structures. The code is available open source within the <i>pymatgen</i> package and the software can as well be used through a web app available on http://crystaltoolkit.org through the Materials Project. | David Waroquiers; Janine George; Matthew Horton; Stephan Schenk; Kristin Persson; Gian-Marco Rignanese; Xavier Gonze; Geoffroy Hautier | Bonding; Coordination Chemistry (Inorg.); Ligands (Inorg.); Solid State Chemistry; Theory - Inorganic; Crystallography – Inorganic | CC BY NC ND 4.0 | CHEMRXIV | 2019-12-17 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/60c746890f50db5f8339647d/original/chem-env-a-fast-and-robust-coordination-environment-identification-tool.pdf |
60c740a6bdbb892770a381cf | 10.26434/chemrxiv.7808351.v1 | FIDDLE. Simultaneous Indexing and Structure Solution from Powder Diffraction Data using a Genetic Algorithm and Correlation Functions | A method for the determination of crystal structures from powder diffraction data is presented that circumvents the difficulties associated with separate indexing. For the simultaneous optimization of the parameters that describe a crystal structure a genetic algorithm is used together with a pattern matching technique based on auto and cross correlation functions.<br /> | Carmen Guguta; Jan M.M. Smits; Rene de Gelder | Computational Chemistry and Modeling; Chemoinformatics - Computational Chemistry; Structure | CC BY NC ND 4.0 | CHEMRXIV | 2019-03-07 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/60c740a6bdbb892770a381cf/original/fiddle-simultaneous-indexing-and-structure-solution-from-powder-diffraction-data-using-a-genetic-algorithm-and-correlation-functions.pdf |
626001c8bdc9c2682edc47c4 | 10.26434/chemrxiv-2022-r4636 | Singlet fission as a polarized spin generator for biological nuclear hyperpolarization | Singlet fission (SF), converting a singlet excited state into a spin-correlated triplet-pair state, is the sole way to generate a spin quintet state in organic materials. Although its application to photovoltaics as an exciton multiplier has been extensively studied, use of its unique spin degree of freedom is largely unexplored. Here, we demonstrate that the spin polarization of the quintet multiexcitons generated by SF improves the sensitivity of biological magnetic resonance through dynamic nuclear polarization (DNP). We form supramolecular assemblies of a few pentacene chromophores and use SF-born quintet spins to achieve DNP of water-glycerol, the most basic biological matrix, at lower microwave intensities than for conventional triplet-based DNP. Our demonstration opens a new use of SF as a “polarized spin generator” in bio-quantum technology. | Yusuke Kawashima; Tomoyuki Hamachi; Akio Yamauchi; Koki Nishimura; Yuma Nakashima; Saiya Fujiwara; Nobuo Kimizuka; Tomohiro Ryu; Tetsu Tamura; Masaki Saigo; Ken Onda; Shunsuke Sato; Yasuhiro Kobori; Kenichiro Tateishi; Tomohiro Uesaka; Go Watanabe; Kiyoshi Miyata; Nobuhiro Yanai | Materials Science | CC BY NC ND 4.0 | CHEMRXIV | 2022-04-21 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/626001c8bdc9c2682edc47c4/original/singlet-fission-as-a-polarized-spin-generator-for-biological-nuclear-hyperpolarization.pdf |
6419b7582bfb3dc2511f9df6 | 10.26434/chemrxiv-2023-mjxcz | Ultra-sensitive selective detection of HopQ protein as a biomarker for Helicobacter pylori bacteria by an electrochemical voltammetric sensor | Background Helicobacter pylori (H. pylori) is a highly contagious pathogenic bacterium that can cause gastrointestinal ulcers and may gradually lead to gastric cancer. H. pylori expresses the outer membrane HopQ protein at the earliest stages of infection. Therefore, HopQ is a highly reliable candidate as a biomarker for H. pylori detection in saliva samples.
Materials and Methods: An H. pylori immunosensor is developed based on detecting HopQ as a biomarker in saliva by a screen-printed carbon electrode (SPCE) modified with MWCNT-COOH decorated with gold nanoparticles (AuNP). The HopQ antibodies are grafted on the SPCE/MWCNT/AuNP surface using EDC/S-NHS chemistry. The sensor performance is investigated by various methods and H. pylori detection performance in spiked saliva samples is evaluated by square wave voltammetry.
Results: The sensor is suitable for HopQ detection with high sensitivity and excellent linearity in the 10 pg/mL - 100 ng/mL range and with a 10 pg/ml limit of detection. The sensor was tested in saliva at 10 ng/mL and returned an 107.6% recovery. The dissociation constant Kd for HopQ/HopQ antibody interaction, estimated from Hill's model, is calculated with a value of an order of
4.605 × 10−10 mg/mL.
Conclusions: Due to the strategical choice of biomarker, the utilization of nanocomposite material to enhance the SPCE electrical performance, the intrinsic selectivity of the antibody-antigen interaction, and effective immobilization, the fabricated platform shows high selectivity, good stability, reproducibility, and cost-effectiveness for early H. pylori detection. Additionally, we provide insight into possible future aspects the researchers are recommended to focus on. | Hussamaldeen Jaradat; Ammar Al-Hamry; Mohammed Ibbini2; Najla Fourati; Olfa Kanoun | Physical Chemistry; Analytical Chemistry; Nanoscience; Electrochemical Analysis; Nanodevices; Nanofabrication | CC BY NC ND 4.0 | CHEMRXIV | 2023-06-02 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/6419b7582bfb3dc2511f9df6/original/ultra-sensitive-selective-detection-of-hop-q-protein-as-a-biomarker-for-helicobacter-pylori-bacteria-by-an-electrochemical-voltammetric-sensor.pdf |
645e1a0da32ceeff2d85be29 | 10.26434/chemrxiv-2023-rrj7x | Direct Mechanocatalysis without Milling Media – From Mixer Mills to Resonant Accoustic Mixers | Here we describe the development of a sustainable and cost-effective approach for catalytic cross-coupling reactions in mechanochemistry. It is found that the substrate's impact with the vessel wall alone is sufficient to initiate the reaction, indicating that milling balls primarily serve as mixing agents rather than energy carriers. The absence of milling balls can be offset by adjusting the rheology using liquid-assisted grinding (LAG). The η-sweet spot of 0.25 μl/mg is confirmed for both resonance acoustic mixer (RAM) and ball-free mixer mills and is higher than in the presence of milling balls. The RAM exhibits excellent performance in the Suzuki reaction, achieving yields of 90% after 60 minutes and complete conversion after 90 minutes. The longevity of the milling vessel is significantly improved in the RAM, allowing for at least 20 reactions without deterioration. | Maximilian Wohlgemuth; Sarah Schmidt; Maike Mayer; Wilm Pickhardt; Sven Graetz; Lars Borchardt | Organic Chemistry; Catalysis; Heterogeneous Catalysis; Homogeneous Catalysis | CC BY NC 4.0 | CHEMRXIV | 2023-05-12 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/645e1a0da32ceeff2d85be29/original/direct-mechanocatalysis-without-milling-media-from-mixer-mills-to-resonant-accoustic-mixers.pdf |
61cad9b51e13ebb5b608b7e7 | 10.26434/chemrxiv-2021-nd0r2-v2 | Covalent Bonding Aptamer with Enhanced SARS-CoV-2 RBD-ACE2 Blocking and Pseudovirus Neutralization Activities | SARS-CoV-2 uses its spike protein receptor-binding domain (RBD) to interact with the angiotensin-converting enzyme 2 (ACE2) receptor on host cells. Inhibitors of the RBD-ACE2 interaction are therefore promising drug candidates in treating COVID-19. Here, we report a covalent bonding aptamer that can block the RBD-ACE2 interaction and neutralize SARS-CoV-2 pseudovirus infection by forming covalent bonds on RBD, resulting in more than 25-fold enhancement of pseudovirus neutralization efficacy over the original binding aptamer. The chemically modified aptamer is equipped with sulfur(VI) fluoride exchange (SuFEx) modifications and covalently targets important RBD residues within the RBD-ACE2 binding interface, including Y453 and R408. The covalent bonding is highly specific to RBD over other proteins such as human serum albumin (HSA), ACE2 and immunoglobulin G1 (IgG1) Fc. Our study demonstrates the promise of introducing covalent inhibition mechanisms for developing robust RBD-ACE2 inhibitors against SARS-CoV-2 infection. | Zichen Qin; Yiying Zhu; Yu Xiang | Biological and Medicinal Chemistry; Organic Chemistry; Biochemistry; Chemical Biology | CC BY NC ND 4.0 | CHEMRXIV | 2021-12-28 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/61cad9b51e13ebb5b608b7e7/original/covalent-bonding-aptamer-with-enhanced-sars-co-v-2-rbd-ace2-blocking-and-pseudovirus-neutralization-activities.pdf |
60c745beee301c7318c793ac | 10.26434/chemrxiv.9642071.v2 | GPU-Accelerated Implementation of Continuous Constant pH Molecular Dynamics in Amber: pKa Predictions with Single-pH Simulations | This paper reports a GPU-accelerated implementation and testing data of the generalized Born based continuous constant pH molecular dynamics method in the Amber package. | Robert C. Harris; Jana Shen; Yandong Huang | Computational Chemistry and Modeling; Theory - Computational | CC BY NC ND 4.0 | CHEMRXIV | 2019-10-25 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/60c745beee301c7318c793ac/original/gpu-accelerated-implementation-of-continuous-constant-p-h-molecular-dynamics-in-amber-p-ka-predictions-with-single-p-h-simulations.pdf |
60c74338469df4ec54f4312b | 10.26434/chemrxiv.8574416.v2 | State Selective Dynamics of TiO2 Charge Carrier Trapping and Recombination | <p>Time-resolved pump-probe photoemission
spectroscopy has been used to study the dynamics of charge carrier
recombination and trapping on hydroxylated rutile TiO<sub>2</sub>(110). Two
types of pump excitation were employed, one in the infrared (0.95 eV) and the
other in the UV (3.5 eV) region. With IR excitation, electrons associated with
defects are excited into the bottom of the conduction band from the polaronic
states within the band gap, which are retrapped within 45±10 fs. Under UV excitation, the electrons in these band gap states and
valence band electrons are excited into the conduction band. In addition to the
fast polaron trapping observed with IR excitation, we also observe a long
lifetime (about 1 ps) component to both the depletion of hot electrons at the
bottom of the conduction band and the refilling of the band gap states. This
points to a band gap state mediated recombination process with a ps lifetime.</p> | Yu Zhang; Daniel T. Payne; Chi L. Pang; Cephise Cacho; Richard T. Chapman; Emma Springate; Helen Fielding; Geoff Thornton | Photochemistry (Physical Chem.); Physical and Chemical Properties; Spectroscopy (Physical Chem.) | CC BY NC ND 4.0 | CHEMRXIV | 2019-07-15 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/60c74338469df4ec54f4312b/original/state-selective-dynamics-of-ti-o2-charge-carrier-trapping-and-recombination.pdf |
67210075f9980725cf45b9cf | 10.26434/chemrxiv-2024-tp7rh | A Deep Learning with Expert Augmentation Approach for Route Scoring in Organic Synthesis | The selection of efficient multi-step synthesis routes is a fundamental challenge in organic synthesis. Comparing different routes involves numerous parameters, economic considerations, and the integration of nuanced chemical knowledge. While computer-aided synthesis planning (CASP) tools can generate synthetic routes, evaluating their overall feasibility and quality continues to rely heavily on human expertise, often lacking consistency and reproducibility. To address this, we have developed a data-driven scoring model that incorporates significant human input. Experts selected key synthesis aspects to score and determined the most representative features of chemical knowledge. The model produces target-specific, generalizable scores for synthetic routes, achieving a top-1 ranking accuracy of 60 \% when benchmarked against experimental data. Evaluation bins, defined by human experts, were incorporated into the final score alongside route length, ensuring a comprehensive assessment. We demonstrate that this criterion and the resulting route rankings align with expert judgment and synthesis feasibility, learned from published reaction data. | Guo Yujia; Mikhail Kabeshov; Tat Hong Duong Le; Samuel Genheden; Giulia Bergonzini; Ola Engkvist; Samuel Kaski | Theoretical and Computational Chemistry; Organic Chemistry; Organic Synthesis and Reactions; Machine Learning | CC BY 4.0 | CHEMRXIV | 2024-11-08 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/67210075f9980725cf45b9cf/original/a-deep-learning-with-expert-augmentation-approach-for-route-scoring-in-organic-synthesis.pdf |
64e37e3700bbebf0e68dd9c4 | 10.26434/chemrxiv-2023-7r7qn-v4 | Geometry Optimization: A Comparison of Different Open-Source Geometry Optimizers | Based on a series of energy minimizations with starting structures obtained from the Baker test set of 30 organic molecules, a comparison is made between various open-source geometry optimization codes that are interfaced with the open-source QUantum Interaction Computational Kernel (QUICK) program for gradient and energy calculations. The findings demonstrate how the choice of the coordinate system influences the optimization process to reach an equilibrium structure. With fewer steps, internal coordinates outperform Cartesian coordinates while the choice of the initial Hessian and Hessian update method in quasi-Newton approaches made by different optimization algorithms also contributes to the rate of convergence. Furthermore, an available open-source machine learning method based on Gaussian Process Regression (GPR) was evaluated for energy minimizations over surrogate potential energy surfaces with both Cartesian and internal coordinates, with internal coordinates outperforming Cartesian. Overall, geomeTRIC and DL-FIND with their default optimization method as well as with GPR-based model using Hartree--Fock theory with the 6-31G** basis set, needed a comparable number of geometry optimization steps to the approach of Baker using a unit matrix as the initial Hessian to reach the optimized geometry. On the other hand, the Berny and Sella offerings in ASE outperformed the other algorithms. Based on this we recommend using the file-based approaches, ASE/Berny and ASE/Sella, for large-scale optimization efforts, while if using a single executable is preferable, we now distribute QUICK integrated with DL-FIND. | Akhil Shajan; Madushanka Manathunga; Andreas Goetz; Kenneth Merz | Theoretical and Computational Chemistry; Computational Chemistry and Modeling; Theory - Computational | CC BY 4.0 | CHEMRXIV | 2023-08-22 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/64e37e3700bbebf0e68dd9c4/original/geometry-optimization-a-comparison-of-different-open-source-geometry-optimizers.pdf |
60c74ffdbdbb892f60a39e63 | 10.26434/chemrxiv.12975014.v1 | Relaxometry Models Compared with Bayesian Technique: Ganglioside Micelle Example | <div>
<div>
<div>
<p>In this work a methodology to perform Bayesian model-comparison is developed and exemplified
in the analysis of magnetic relaxation dispersion (NMRD) experiments of water in Ganglioside
micelle system. The NMRD powerful probe of slow dynamics in complex liquids is obtained.
There are many interesting systems to study with NMRD, such as ionic and Lyotropic liquids
or electrolytes. However, to progress in the understanding of the physical chemistry of studied
systems relatively detailed theoretical NMRD-models are required. To improve the models they
need to be carefully compared, in addition to physico-chemical considerations of molecular and
spin dynamics. The comparison is performed by computing the Bayesian evidence in terms of a
thermodynamic integral solved with Markov chain Monte Carlo. The result leads to a conclusion
of two micelle water sites, and rules out lower and higher complexity level, i.e., one and three
sites. In contrast, and provided only with the quality of best fit, suggest a three site model. The
two approximate selection tools, Akaike and Baysian information criterions, may lead to wrong
conclusions compared to the the full integration. The methodology is expected to be one of
several important tools in NMRD model development, however, is completely general and should
find awakened use in many research areas.
</p>
</div>
</div>
</div> | Pär Håkansson | Surfactants; Biophysical Chemistry; Interfaces; Self-Assembly; Spectroscopy (Physical Chem.) | CC BY NC ND 4.0 | CHEMRXIV | 2020-10-12 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/60c74ffdbdbb892f60a39e63/original/relaxometry-models-compared-with-bayesian-technique-ganglioside-micelle-example.pdf |
630265aa90802d15cd64981a | 10.26434/chemrxiv-2022-wh9nz-v4 | Poly(butylene-succinate)-based blends with enhanced oxygen permeability | Poly(butylene succinate) (PBS) is a biodegradable polymer produced from renewable raw materials and is widely used in the production of packaging materials. Among important features, oxygen permeability is crucial for “breathing” packaging materials (such as packaging for medical devices sterilized with gaseous ethylene oxide). Recently, poly(butylene succinate-dilinolene succinate) (PBS-DLS) copolymers containing long chains of fatty acids and showing excellent elasticity were synthesized. In this work, bio-based polymer blends of PBS and PBS-DLS copolymer with an aliphatic-aromatic poly(butylene terephthalate-butylene adipate) (PBAT) (Ecoflex) were prepared in order to further improve their oxygen permeability while maintaining mechanical stability. PBS and PBS-DLS copolymer containing 90 wt% of hard segments and 10 wt% of soft segments, respectively, were used for blends preparation with 10 wt% of PBAT. The chemical structure was analyzed using infrared spectroscopy and thermal properties were determined with differential scanning calorimetry. The introduction of PBAT to the blends did not affect their melting temperatures. PBS-based blends were miscible at the molecular level based on single Tg value calculated from Fox equation and uniform fracture surface morphology from scanning electron microscopy (SEM). Importantly, the oxygen permeability of PBS-DLS/PBAT blend was comparable to non-biodegradable high-density polyethylene (HDPE) Tyvek used for medical devices packaging. | Nina Kantor-Malujdy; Sandra Skowron; Beata Michalkiewicz; Miroslawa El Fray | Materials Science; Biodegradable Materials; Elastic Materials; Materials Processing | CC BY 4.0 | CHEMRXIV | 2022-08-22 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/630265aa90802d15cd64981a/original/poly-butylene-succinate-based-blends-with-enhanced-oxygen-permeability.pdf |
60c74f71337d6c610ae28146 | 10.26434/chemrxiv.12902288.v1 | Assigning the Origin of Microbial Natural Products by Chemical Space Map and Machine Learning | <p>Microbial natural
products (NPs) are an important source of drugs. However, their structural
diversity remains poorly understood. Here we used our recently reported MinHashed
Atom
Pair
fingerprint with diameter of
four bonds (MAP4), a fingerprint suitable for
molecules across very different sizes, to analyze the Natural Products Atlas (NPAtlas), a
database of 25,523 NPs of bacterial or fungal origin downloaded from <a href="https://www.npatlas.org/joomla/">https://www.npatlas.org/joomla/</a>.
To visualize NPAtlas by MAP4 similarity, we used the dimensionality reduction
method tree map (TMAP) (<a href="http://tmap.gdb.tools/">http://tmap.gdb.tools</a>).
The resulting interactive map (<a href="https://tm.gdb.tools/map4/npatlas_map_tmap/">https://tm.gdb.tools/map4/npatlas_map_tmap/</a>)
organizes molecules by physico-chemical properties and compound families such
as peptides, glycosides, polyphenols or terpenoids. Remarkably, the map separates
bacterial and fungal NPs from one another, revealing that these two compound
families are intrinsically different despite of their related biosynthetic
pathways. We used these differences to train a machine learning model capable
of distinguishing between NPs of bacterial or fungal origin. </p> | Alice Capecchi; Jean-Louis Reymond | Machine Learning; Chemoinformatics - Computational Chemistry | CC BY NC ND 4.0 | CHEMRXIV | 2020-09-02 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/60c74f71337d6c610ae28146/original/assigning-the-origin-of-microbial-natural-products-by-chemical-space-map-and-machine-learning.pdf |
60c75210842e6538f9db3c8d | 10.26434/chemrxiv.13249889.v1 | Activation of Ammonia and Hydrazine by Electron Rich Fe(II) Complexes Supported by a Dianionic Pentadentate Ligand Platform Through a Common Terminal Fe(III) Amido Intermediate | We report the use of electron rich iron complexes supported by a dianionic diborate
pentadentate ligand system, B2Pz4Py, for the coordination and activation of ammonia (NH3) and
hydrazine (NH2NH2). For ammonia, coordination to neutral (B2Pz4Py)Fe(II) or cationic
[(B2Pz4Py)Fe(III)]+ platforms leads to well characterized ammine complexes from which
hydrogen atoms or protons can be removed to generate, fleetingly, a proposed (B2Pz4Py)Fe(III)-
NH2 complex (3Ar-NH2). DFT computations suggest a high degree of spin density on the amido
ligand, giving it significant aminyl radical character. It rapidly traps the H atom abstracting agent
2,4,6-tri-tert-butylphenoxy radical (ArO•) to form a C-N bond in a fully characterized product
(2Ar), or scavenges hydrogen atoms to return to the ammonia complex (B2Pz4Py)Fe(II)-NH3 (1ArNH3). Interestingly, when (B2Pz4Py)Fe(II) is reacted with NH2NH2, a fully characterized bridging
diazene complex, 4Ar, is formed along with ammonia adduct 1Ar-NH3 as the spectroscopically
observed (-78˚C) (B2Pz4Py)Fe(II)-NH2NH2-Fe(II)( B2Pz4Py) dimer (1Ar)2-NH2NH2 is allowed to
warm to room temperature. Experimental and computational evidence is presented to suggest
that (B2Pz4Py)Fe(II) induces reductive cleavage of the N-N bond in hydrazine to produce the
Fe(III)-NH2 complex 3Ar-NH2, which abstracts H• atoms from (1Ar)2-NH2NH2 to generate the
observed products. All of these transformations are relevant to proposed steps in the ammonia
oxidation reaction, an important process for the use of nitrogen-based fuels enabled by
abundant first row transition metals.
<br /> | Lucie Nurdin; Yan Yang; Peter Neate; Warren Piers; Laurent Maron; Michael L. Neidig; Jian-Bin Lin; Benjamin
S. Gelfand | Coordination Chemistry (Inorg.); Kinetics and Mechanism - Inorganic Reactions; Small Molecule Activation (Inorg.); Theory - Inorganic | CC BY NC ND 4.0 | CHEMRXIV | 2020-11-18 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/60c75210842e6538f9db3c8d/original/activation-of-ammonia-and-hydrazine-by-electron-rich-fe-ii-complexes-supported-by-a-dianionic-pentadentate-ligand-platform-through-a-common-terminal-fe-iii-amido-intermediate.pdf |
657f53429138d23161e4550e | 10.26434/chemrxiv-2023-xgt42 | Simplifying Access to Targeted Protein Degraders via Ni-Electrocatalytic Cross-Coupling | C–C linked glutarimide-containing structures with direct utility in the preparation of cereblon-based degraders (PROTACs, CELMoDs) can be assessed in a single step from inexpensive, commercial -bromoglutaramide through a unique Brønsted-acid assisted Ni-electrocatalytic approach. The reaction tolerates a broad array of functional groups that are historically problematic and can be applied to the simplified synthesis of dozens of known compounds that have only been procured through laborious, wasteful, multistep sequences. The reaction is scalable in both batch and flow and features a trivial procedure wherein the most time-consuming aspect of reaction setup is weighing out the starting materials. | Philipp Neigenfind ; Luca Massaro ; Áron Péter ; Andrew Degnan ; Megan Emmanuel ; Martins Oderinde ; Chi He ; David Peters ; Tamara Ewing ; Yu Kawamata; phil baran | Biological and Medicinal Chemistry; Organic Chemistry; Catalysis; Organic Synthesis and Reactions; Drug Discovery and Drug Delivery Systems; Electrocatalysis | CC BY 4.0 | CHEMRXIV | 2023-12-20 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/657f53429138d23161e4550e/original/simplifying-access-to-targeted-protein-degraders-via-ni-electrocatalytic-cross-coupling.pdf |
653cb65e48dad231208f68dd | 10.26434/chemrxiv-2023-j8ndj | Enhanced flow in deformable carbon nanotubes | Water transport through nanopores is widespread in the natural world and holds significant implications in various technological applications. Several researchers observed a significant increase in water flow through graphene-based nanotubes. Graphene sheets are deformable, so we represent nano/Angstrom-size tubes with a deformable wall model using the small displacement structural mechanics with a linear pressure-area relationship. We assume the lubrication assumption in the shallow tubes, and using the microstructure of confined water along with slip at the capillary boundaries, we derive the model for deformable nanotubes. Our derived model also facilitates the flow dynamics of Newtonian fluids under different conditions as its limiting cases, which have been previously reported in the literature. We compare the predictions by our deformable-wall and rigid-wall model with the experimental results and the MD simulation predictions by multiple literatures. Many studies were well-predicted by the rigid-wall model with slips. However, we find that there are many studies with high porosity and thin wall tubes, where elasticity or deformability of the tube is essential in modelling, which is well-predicted by our deformable-wall model with slips. In our study, we focus on investigating the impact of two key factors: the deformability of the nanotubes and the slip length on the flow rate. We find that the flow rate inside the tube increases as the deformability $1/\alpha$ increases (or corresponding thickness $\mathcal{T}$ and elastic modulus $E$ of the wall decreases). We find that the flow rate in deformable tubes scales as $\dot{m}_{\text{deformable}}\sim 1/\alpha^0 $ for $\Big ( \Delta p/\alpha A_o \Big ) \ll 1$, $\dot{m}_{\text{deformable}}\sim 1/\alpha $ for $\Big ( \Delta p/\alpha A_o \Big ) \sim O(10^{-1})$ and $\dot{m}_{\text{deformable}}\sim \alpha^2 $ for $\Big ( \Delta p/\alpha A_o \Big ) \sim O(1)$. We also find that, for a given deformability factor $\alpha$, the percentage change in flow rate in the smaller diameter of the tube is much larger than the larger diameter. As the tube diameter decreases for the given reservoir pressure, $\Delta \dot{m}/\dot{m}$ increases $A_o^{-1}$ followed by $A_o^{-2}$ after a threshold with the tube diameter. We find that for the rigid tube, where the deformability parameter $1/\alpha=0$, the mass flow rate varies linearly, i.e., $\dot{m}_{\text{rigid}} \sim \Delta p $, whereas for the deformable tubes, the flow rate scales as $\dot{m}_{\text{deformable}}\sim \Delta p^2 $ for $ \Big ( \Delta p/\alpha A_o \Big ) \sim O(10^{-1})$ during transition from $\dot{m}_{\text{rigid}} \sim \Delta p $ to $\sim \Delta p^3 $, and finally to $\dot{m}_{\text{deformable}}\sim \Delta p^3 $ for $ \Big ( \Delta p/\alpha A_o \Big ) \sim O(1)$. We further find that the slip also significantly increases the mass flow rate in the nanotubes. Still, the deformability has, in comparison, a more substantial effect in increasing the mass flow rate to several orders than the slips. | Ashish Garg | Nanoscience; Nanodevices; Nanofluidics; Nanostructured Materials - Nanoscience | CC BY NC ND 4.0 | CHEMRXIV | 2023-10-31 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/653cb65e48dad231208f68dd/original/enhanced-flow-in-deformable-carbon-nanotubes.pdf |
60c740e6702a9bdf3718a190 | 10.26434/chemrxiv.6199304.v2 | Enthalpies of formation of the benzyloxyl, benzylperoxyl, hydroxyphenyl radicals and related species on the potential energy surface for the reaction of toluene with the hydroxyl radical | <p></p><p>The reaction of toluene (T) with OH<sup>●</sup>
produces addition products as well as the benzyl radical (TR). TR can react
with OH<sup>●</sup> or O<sub>2</sub> to produce oxygenated species, for many of
which there is no experimental information available. We present here theoretically
determined heats of formation (HFs) of 17 such species using the non-isodesmic
reactions on the potential energy surface (PES) of TR+O<sub>2</sub> and T+OH<sup>●</sup>+O<sub>2</sub>.
For those species the experimental HFs of which are known, we obtained a good
correlation between experimental and theoretical values at the G4 (r<sup>2</sup>=0.999)
and M06/cc-pVQZ (r<sup>2</sup>=0.997) levels, thus showing the goodness of the
methods used. Previously unknown HFs of other radicals (benzyloxyl, spiro
[1,2-dioxetane benzyl], hydroxyphenyl, and benzylperoxyl) and closed shell
species (salicylic alcohol, benzo[b]oxetane and p-hydroxy cyclohexa-2,5-dienone)
were later determined using those methods.<b></b></p><br /><p></p> | Oscar Ventura; Martina Kieninger; Zoi Salta; Agnie M. Kosmas; Vincenzo Barone | Computational Chemistry and Modeling; Quantum Mechanics; Thermodynamics (Physical Chem.) | CC BY NC ND 4.0 | CHEMRXIV | 2019-03-05 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/60c740e6702a9bdf3718a190/original/enthalpies-of-formation-of-the-benzyloxyl-benzylperoxyl-hydroxyphenyl-radicals-and-related-species-on-the-potential-energy-surface-for-the-reaction-of-toluene-with-the-hydroxyl-radical.pdf |
640446939789de3dd9f1cb36 | 10.26434/chemrxiv-2022-z0t4g-v3 | UmetaFlow: An untargeted metabolomics workflow for high-throughput data processing and analysis | Metabolomics experiments generate highly complex datasets, which are time and work-intensive, sometimes even error-prone if inspected manually. Therefore, new methods for automated, fast, reproducible, and accurate data processing and dereplication are required. Here, we present UmetaFlow, a computational workflow for untargeted metabolomics that combines algorithms for data pre-processing, spectral matching, molecular formula and structural predictions, and an integration to the GNPS workflows Feature-Based Molecular Networking and Ion Identity Molecular Networking for downstream analysis. UmetaFlow is implemented as a Snakemake workflow, making it easy to use, scalable, and reproducible. For more interactive computing, visualization, as well as development, the workflow is also implemented in Jupyter notebooks using the Python programming language and a set of Python bindings to the OpenMS algorithms (pyOpenMS). Finally, UmetaFlow is also offered as a web-based Graphical User Interface for parameter optimization and processing of smaller-sized datasets. UmetaFlow was validated with in-house LC-MS/MS datasets of actinomycetes producing known secondary metabolites, as well as commercial standards, and it detected all expected features and accurately annotated 76% of the molecular formulas and 65% of the structures. As a more generic validation, the publicly available MTBLS733 and MTBLS736 datasets were used for benchmarking, and UmetaFlow detected more than 90% of all ground truth features and performed exceptionally well in quantification and discriminating marker selection. We anticipate that UmetaFlow will provide a useful platform for the interpretation of large metabolomics datasets. | Eftychia Eva Kontou; Axel Walter; Oliver Alka; Julianus Pfeuffer; Timo Sachsenberg; Omkar S. Mohite; Matin Nuhamunada; Oliver Kohlbacher; Tilmann Weber | Biological and Medicinal Chemistry; Analytical Chemistry; Chemoinformatics; Mass Spectrometry; High-throughput Screening | CC BY 4.0 | CHEMRXIV | 2023-03-06 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/640446939789de3dd9f1cb36/original/umeta-flow-an-untargeted-metabolomics-workflow-for-high-throughput-data-processing-and-analysis.pdf |
65d90446e9ebbb4db913fc1c | 10.26434/chemrxiv-2024-6x271 | Coarse-Grained Simulation of mRNA-Loaded Lipid Nanoparticle Self-Assembly | Ionizable lipid-containing lipid nanoparticles (LNPs) have enabled the delivery of RNA for a range of therapeutic applications. In order to optimize safe, targeted and effective LNP-based RNA delivery platforms, an understanding of the role of composition and pH in their structural properties and self-assembly is crucial, yet there have been few computational studies of such phenomena. Here we present a coarse-grained model of ionizable lipid and mRNA-containing LNPs. Our model allows access to the large length- and time-scales necessary for LNP self-assembly, and is mapped and parameterized with reference to all-atom structures and simulations of the corresponding components at compositions typical of LNPs used for mRNA delivery. Our simulations reveal insights into the dynamics of self-assembly of such mRNA-encapsulating LNPs, as well as the subsequent pH change-driven LNP morphology and release of mRNA. | Douglas Grzetic; Nicholas Hamilton; John Shelley | Theoretical and Computational Chemistry; Computational Chemistry and Modeling | CC BY NC ND 4.0 | CHEMRXIV | 2024-02-26 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/65d90446e9ebbb4db913fc1c/original/coarse-grained-simulation-of-m-rna-loaded-lipid-nanoparticle-self-assembly.pdf |
6588369c66c1381729f085da | 10.26434/chemrxiv-2023-jrms3 | Long-range electron proton coupling in respiratory complex I – insights from molecular simulations of the quinone chamber and antiporter-like subunits | Respiratory complex I is a redox-driven proton pump. Several high-resolution structures of complex I have been determined providing important information about the putative proton transfer paths and conformational transitions that may occur during catalysis. However, how redox energy is coupled to the pumping of protons remains unclear. In this article, we review biochemical, structural and molecular simulation data on complex I and discuss several coupling models of complex I, including the key unresolved mechanistic questions. Focusing both on the quinone-reductase domain as well as the proton-pumping membrane-bound domain of complex I, we discuss a molecular mechanism of proton pumping that satisfies most experimental and theoretical constraints. We suggest that protonation reactions play an important role not only in catalysis, but also in the physiologically-relevant active/deactive transition of complex I. | Amina Djurabekova; Jonathan Lasham; Oleksii Zdorevskyi; Volker Zickermann; Vivek Sharma | Theoretical and Computational Chemistry; Biological and Medicinal Chemistry; Biochemistry; Biophysics; Computational Chemistry and Modeling | CC BY 4.0 | CHEMRXIV | 2023-12-27 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/6588369c66c1381729f085da/original/long-range-electron-proton-coupling-in-respiratory-complex-i-insights-from-molecular-simulations-of-the-quinone-chamber-and-antiporter-like-subunits.pdf |
67a5a55e81d2151a0278daa1 | 10.26434/chemrxiv-2025-wd5jw | Predicting Pore Limiting Diameter in Metal-Organic Frameworks Using Only Metal-Linker Building Blocks | Metal-organic frameworks (MOFs) show important potential in applications such as gas storage, catalysis, and drug delivery. However, the vast chemical space of MOFs makes experimental exploration impractical. While existing computational models often require the full MOF structure to predict key properties, we introduce a deep learning approach that predicts the pore limiting diameter (PLD) using only the metal-linker building blocks. Our method employs a 3D convolutional neural network (CNN) trained on spatial features derived from the 3D coordination of atoms within metal-linker complexes. We constructed a dataset of 25,529 MOFs from CoREMOF-2019 and Tobacco databases, deconstructed them into metal-linker units, and applied voxelization to generate 3D features. These features were then used to train a 3D CNN model, achieving an R² value of 0.86 on an unseen test set. By enabling accurate PLD prediction without requiring the full MOF structure, our approach facilitates early-stage screening and rational design of MOFs. The data and source code for our model are available at https://github.com/ClinicalAI/MOF_LPD_Prediction. | Mohamad Koohi-Moghadam; Ahmad Mohammadi; Hongyan Li; Hongzhe Sun | Theoretical and Computational Chemistry; Inorganic Chemistry; Bioinorganic Chemistry; Artificial Intelligence | CC BY NC 4.0 | CHEMRXIV | 2025-02-07 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/67a5a55e81d2151a0278daa1/original/predicting-pore-limiting-diameter-in-metal-organic-frameworks-using-only-metal-linker-building-blocks.pdf |
60c7533abb8c1af3233dbfe3 | 10.26434/chemrxiv.13334006.v2 | A Nanodiamond-Based Theranostic Agent for Light-Controlled Intracellular Heating and Nanoscale Temperature Sensing | Temperature is an essential factor in all biological processes and most of the biological activities are related to temperature. However, information about the temperature in living cells are limited. In photothermal therapy, an emerging cancer treatment due to its high spatial control and non-invasive nature, the local effect of intracellular temperature change is not well understood. Fluorescent nanodiamonds (ND) are a unique carbon material possessing optical defects inside the carbon lattice that enable sensing of temperature on a nanoscale completely independent of external conditions. Herein, we coat ND with polymers to form a nanogel shell around NDs that can absorb indocyanine green, a common photothermal agent, to obtain nanodiamond-nanogel-indocyanine green. Upon irradiation, we not only show successful killing of cancer cells with a high control in space but we are also able to sense the increase in temperature using single NDs as nanothermometers in cells.<br /> | Yingke Wu; Md Noor A Alam; Priyadharshini Balasubramanian; Anna Ermakova; Stefan Fischer; Holger Barth; Manfred Wagner; Marco Raabe; Fedor Jelezko; Tanja Weil | Biocompatible Materials; Coating Materials; Imaging Agents; Optical Materials; Polymer brushes; Bioengineering and Biotechnology | CC BY NC ND 4.0 | CHEMRXIV | 2020-12-15 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/60c7533abb8c1af3233dbfe3/original/a-nanodiamond-based-theranostic-agent-for-light-controlled-intracellular-heating-and-nanoscale-temperature-sensing.pdf |
60c741a79abda223d8f8beba | 10.26434/chemrxiv.8079620.v1 | Employing Exfoliated Graphite as Novel Support Material for Heterogeneous Model Catalysts | <p>The inert nature of graphitic samples allows for
characterisation of rather isolated supported nanoparticles in model catalysts,
as long as sufficiently large inter-particle distances are obtained. However, the
low surface area of graphite and the little interaction with nanoparticles
result in a challenging application of conventional preparation routes in
practice. In the present study, a set of graphitic carbon materials was characterised
in order to identify potential support materials for the preparation of model
catalyst systems. Various sizes of well-defined Co<sub>3</sub>O<sub>4</sub>
nanoparticles were synthesised separately and supported onto exfoliated graphite
powder, that is graphite after solvent-assisted exfoliation <i>via</i> ultrasonication resulting in thinner
flakes with increased specific surface area. The developed model catalysts are
ideally suited for sintering studies of isolated nano-sized cobaltous particles
as the graphitic support material does not provide distinct metal-support
interaction. Furthermore, the differently sized cobaltous particles in the
various model systems render possible studies on structural dependencies of
activity, selectivity, and deactivation in cobalt oxide or cobalt catalysed
reactions.</p> | Moritz Wolf; Nico Fischer; Michael Claeys | Carbon-based Materials; Catalysts; Nanocatalysis - Catalysts & Materials; Spectroscopy (Inorg.); Heterogeneous Catalysis | CC BY NC ND 4.0 | CHEMRXIV | 2019-05-08 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/60c741a79abda223d8f8beba/original/employing-exfoliated-graphite-as-novel-support-material-for-heterogeneous-model-catalysts.pdf |
60c74227469df4d534f42f43 | 10.26434/chemrxiv.8217929.v1 | Insights into Non-Covalent Interactions with a Machine-Learned Electron Density | <div>Chemists continuously harvest the power of non-covalent interactions to control phenomena in both the micro- and macroscopic worlds. From the quantum chemical perspective, the strategies essentially rely upon an in-depth understanding of the physical origin of these interactions, the quantification of their magnitude and their visualization in real-space. </div><div>The total electron density rho(r) represents the simplest yet most comprehensive piece of information available for fully characterizing bonding patterns and non-covalent interactions. The charge density of a molecule can be computed by solving the Schrodinger equation, but this approach becomes rapidly demanding if the electron density has to be evaluated for thousands of different molecules or for very large chemical systems, such as peptides and proteins. </div><div>Here we present a transferable and scalable machine-learning model capable of predicting the total electron density directly from the atomic coordinates. The regression model is used to access qualitative and quantitative insights beyond the underlying rho(r) in a diverse ensemble of sidechain-sidechain dimers extracted from the BioFragment database (BFDb). The transferability of the model to more complex chemical systems is demonstrated by predicting and analyzing the electron density of a collection of 8 polypeptides.</div> | Alberto Fabrizio; Andrea Grisafi; Benjamin Meyer; Michele Ceriotti; Clemence Corminboeuf | Computational Chemistry and Modeling; Theory - Computational; Machine Learning | CC BY NC ND 4.0 | CHEMRXIV | 2019-09-03 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/60c74227469df4d534f42f43/original/insights-into-non-covalent-interactions-with-a-machine-learned-electron-density.pdf |
649ae79eba3e99daef1f7956 | 10.26434/chemrxiv-2023-d25gk | Two-color Emissive AIEgens with Anti-Kasha Property for Dual-Organelle Imaging and Phototherapy | Despite the rapid development of probes for targeting single organelle, construction of robust dual-organelle targeting probes with multicolor emission was rarely reported. Towards this end and in consideration of the unique advantages of aggregation-induced emission luminogens (AIEgens), two dual emissive AIEgens with donor-π-acceptor structures were designed and syn-thesized, namely QT-1 and QF-2. Both two AIEgens exhibited excitation wavelength-dependence defying the Kasha’s rule. The invariant near-infrared emission was originated from S1 of AIEgens to S0. However, its anti-Kasha luminescence at a short wavelength from the S2 state can be tuned by changing the excitation wavelength. Given the two-color emission of AIEgens, QT-1 and QF-2 could stain lipid droplets (LDs) and mitochondria in a blue and red fluorescence, respectively. Moreover, thanks to the near-infrared emission and abundant ROS generation efficiency of QT-1, it was chosen as a photodynamic thera-py agent to selectively kill cancer cells from normal cells. Upon light irradiation, obvious decrease of mitochondrial membrane potential (MMP) and serious change of mitochondrial shape in cells were observed, which corresponded to the efficient inhibi-tion of tumor growth in vivo. This work afforded a promising strategy for the construction of multicolor emission by tuning anti-Kasha behaviors and to expand their application in dual-organelle targeting-based phototheranostics. | Pu Chen; Guogang Shan; Qingli Nie; Yuting Yan; Pengfei Zhang; Zujin Zhao; Hai-Tao Feng; Ben Zhong Tang | Biological and Medicinal Chemistry; Analytical Chemistry; Imaging; Cell and Molecular Biology; Chemical Biology; Materials Chemistry | CC BY NC ND 4.0 | CHEMRXIV | 2023-06-28 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/649ae79eba3e99daef1f7956/original/two-color-emissive-ai-egens-with-anti-kasha-property-for-dual-organelle-imaging-and-phototherapy.pdf |
60c73e57567dfeab27ec37ca | 10.26434/chemrxiv.6024410.v2 | Evaluating the London Dispersion Coefficients of Protein Force Fields Using the Exchange-Hole Dipole Moment Model | <div>London dispersion is one of the fundamental intermolecular interactions involved in protein folding and dynamics. The popular CHARMM36, Amber ff14sb, and OPLS-</div><div>AA force fields represent these interactions through the C6 /r 6 term of the Lennard-Jones potential. The C6 parameters are assigned empirically, so these parameters are</div><div>not necessarily a realistic representation of the true dispersion interactions. In this work, dispersion coefficients of all three force fields were compared to corresponding</div><div>values from quantum-chemical calculations using the exchange-hole dipole moment (XDM) model. The force field values were found to be roughly 50% larger than the XDM values for protein backbone and side-chain models. The CHARMM36 and Amber OL15 force fields for nucleic acids were also found to exhibit this trend. To explore how these elevated dispersion coefficients affect predicted properties, the hydration energies of the side-chain models were calculated using the staged REMD-TI method of Deng and Roux for the CHARMM36, Amber ff14sb, and OPLS-AA force fields. Despite having large C 6 dispersion coefficients, these force fields predict side-chain hydration energies that are in generally good agreement with the experimental values, including for hydrocarbon residues where the dispersion component is the dominant attractive solute–solvent interaction. This suggests that these force fields predict the correct total strength of dispersion interactions, despite C6 coefficients that are considerably larger than XDM predicts. An analytical expression for the water–methane dispersion energy using XDM dispersion coefficients shows that that higher-order dispersion terms(i.e., C 8 and C 10 ) account for roughly 37.5% of the hydration energy of methane. This suggests that the C 6 dispersion coefficients used in contemporary force fields are</div><div>elevated to account for the neglected higher-order terms. Force fields that include higher-order dispersion interactions could resolve this issue.</div> | Evan T. Walters; Mohamad Mohebifar; Erin R. Johnson; Christopher Rowley | Computational Chemistry and Modeling; Theory - Computational; Biophysical Chemistry | CC BY NC ND 4.0 | CHEMRXIV | 2018-06-06 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/60c73e57567dfeab27ec37ca/original/evaluating-the-london-dispersion-coefficients-of-protein-force-fields-using-the-exchange-hole-dipole-moment-model.pdf |
650e27d860c37f4f76465a57 | 10.26434/chemrxiv-2023-t2wsn | High Accuracy, ab initio Potential Energy Curves
and Dipole Moment Functions for the X1Σ+ and a3Π Spin States of the CF+ Diatomic Molecule | Potential energy curves and dipole moment functions constructed using high accuracy, ab initio methods allow for an in-depth examination of the electronic structure of diatomic molecules. ab initio methods are invaluable especially for molecules that are difficult to synthesize and examine spectroscopically such as those found in the interstellar medium (ISM) where conditions allow for the longer lifetimes of lower stability molecules. The CF+ diatomic molecule is one such molecule that has been observed spectroscopically in the ISM. Previous experimental and theoretical work have examined different spectroscopic aspects of the CF+ molecule but the development of newer, more complete potential energy curves and dipole moment functions allow for even greater insight. We constructed both potential energy curves and dipole moment functions for the ground X1Σ+ and first excited a3Π states of CF+ for both 12C and 13C isotopologues. The potential energy curves were constructed using coupled cluster with single, double, and perturbative triple excitations (CCSD(T)) at the complete basis set limit with corrections from full triple, quadruple, quintuple, and hextuple excitations within a finite-basis coupled cluster wavefunction as well as corrections from full configuration interaction and relativistic effects. Significant multireference character was identified in
the electronic structure of CF+ which prompted the need for such high-level corrections to the PEC. Rovibrational wavefunctions were calculated using a vibrational Hamiltonian matrix which moves beyond the harmonic oscillator approximation. The equilibrium bond length,
vibrational constant, and rotational constant were reproduced to within 0.00013 Å, 0.28 cm-1 and 0.00045 cm-1, respectively, of experimental values. Experimental transition energies from rovibrational spectra were reproduced with an error no larger than 0.63 cm-1. The triplet excited state (a3Π) was found to lie 4.808 eV (38774.9 cm-1) higher in energy with a slightly elongated bond length of 1.21069 Å. High accuracy rovibrational
line lists for the 12C and 13C isotopologues for both the X1Σ+ and the excited a3Π state were generated. | Gavin McCarver; Robert Hinde | Theoretical and Computational Chemistry; Physical Chemistry; Earth, Space, and Environmental Chemistry; Space Chemistry; Computational Chemistry and Modeling; Quantum Mechanics | CC BY NC ND 4.0 | CHEMRXIV | 2023-09-25 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/650e27d860c37f4f76465a57/original/high-accuracy-ab-initio-potential-energy-curves-and-dipole-moment-functions-for-the-x1-and-a3-spin-states-of-the-cf-diatomic-molecule.pdf |
60c74a3b567dfea528ec4d2a | 10.26434/chemrxiv.12170337.v1 | A Generative Deep Learning Approach for the Discovery of SARS CoV2 Protease Inhibitors | COVID19 has caused thousands of deaths worldwide within a few months. The rapid spread of this virus that causes COVID19, termed SARS CoV2, has been facilitated by the lack of effective vaccines and treatments against this virus. In recent months, our team has developed a novel deep learning platform, Rosalind, for drug design and optimisation, and it enables rapid in silico discovery and evaluation of novel chemical designs. In the current work, we applied Rosalind for the rapid discovery of SARS CoV2 replication inhibitors that target the virus main protease M<sup>pro</sup>. Through a series of training and optimisation rounds based on reported SARS CoV2 M<sup>pro</sup> inhibitors helped by docking into the recently reported crystal structures of SARS CoV2 M<sup>pro </sup>and medicinal chemistry input, we identified the a series of promising SARS CoV2 M<sup>pro </sup>inhibitors. These compounds are presented in this work so they scientific community could pursue them while we continue our deep learning-based work in a collaborative manner to identify lead SARS CoV2 M<sup>pro </sup>compounds with excellent drug-like properties that could be developed in a timely manner to address the urgent need for new and effective COVID19 treatments. | Noor Shaker; Mohamed Abou-Zleikha; Mubarak AlAmri; Youcef Mehellou | Drug Discovery and Drug Delivery Systems | CC BY NC ND 4.0 | CHEMRXIV | 2020-04-23 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/60c74a3b567dfea528ec4d2a/original/a-generative-deep-learning-approach-for-the-discovery-of-sars-co-v2-protease-inhibitors.pdf |
67af4c87fa469535b94eb60e | 10.26434/chemrxiv-2025-h53bc | Zero- to Ultralow-field Control of Hyperpolarized Nuclear Spin Orders in Acetonitrile Solvent | Zero- to ultralow-field (ZULF) nuclear magnetic resonance (NMR) provides ac- cess to untruncated spin-spin interactions and—with its simplified instrumentation demands—emerges as a promising tool for chemical fingerprinting and fundamental physics. However, ZULF NMR J-spectra typically suffer from poor signal-to-noise ra- tios (SNRs) due to the low natural abundance of many heteronuclei. In this work we employ hyperpolarization via Signal Amplification by Reversible Exchange (SABRE) and various preparation, evolution, and signal detection schemes to demonstrate the control of many (10+) hyperpolarized nuclear spin orders in the XA3 spin system di- rectly inside a ZULF apparatus (here X corresponds to the 15N spin and A3 corresponds to the three protons). Acetonitrile solvent with natural isotopic abundance is used as a chemical model of the XA3 system. The results underscore the versatility and precision of ZULF NMR, highlighting its potential for applications in precision chemistry and fundamental physics. | Jingyan Xu; Raphael Kircher; Roman Picazo-Frutos; Dmitry Budker; Danila Barskiy | Physical Chemistry; Analytical Chemistry; Organometallic Chemistry; Analytical Apparatus; Quantum Mechanics; Spectroscopy (Physical Chem.) | CC BY 4.0 | CHEMRXIV | 2025-02-18 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/67af4c87fa469535b94eb60e/original/zero-to-ultralow-field-control-of-hyperpolarized-nuclear-spin-orders-in-acetonitrile-solvent.pdf |
66fed6b3cec5d6c1420f0636 | 10.26434/chemrxiv-2024-dk2f8 | Transparent, ferroelectric Ca:HfO2 and Sr:HfO2 films grown from chemical solution on ITO-coated glass | The discovery of ferroelectricity in HfO2 thin films has revived the interest on ferroelectric-based memories. Yet, other applications like transparent micro sensors and actuators are also potentially possible. By using a simple chemical solution method, we achieved the growth of transparent Ca:HfO2 and Sr:HfO2 films on ITO coated glass and reached polarization values of 12 and 6 µC/cm2, respectively, after deposition of top Pt electrodes. The selection of Ca or Sr as doping element brought about large variations in thermal conditions at which ferroelectricity in doped-HfO2 films was achieved. Sr:HfO2 required significantly shorter annealing times than Ca:HfO2 and caused deformation of the glass substrate despite otherwise equal processing conditions. Moreover, although, both Ca and Sr induced the crystallization of hafnia into high symmetry phases, the latter also enhanced the appearance of the monoclinic structure. Interestingly, high resolution transmission microscopy revealed a semi-epitaxial “cube on cube” growth of doped-HfO2 on individual ITO crystals. This predicts that accomplishing fully epitaxial HfO2 films by a chemical solution method should be possible. Technological innovation might come from achieving fully transparent ferroelectric/piezoelectric HfO2-based devices. | Miguel-Angel Badillo-Avila; Sepide Taleb; Brenda Carreño-Jiménez; Cristian Ferreyra; Taraneh Mokabber; Diego Rubi; Myriam Aguirre; Rebeca Castanedo-Pérez; Gerardo Torres-Delgado; Mónica Acuautla; Beatriz Noheda | Materials Science; Thin Films; Materials Chemistry | CC BY NC 4.0 | CHEMRXIV | 2024-10-07 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/66fed6b3cec5d6c1420f0636/original/transparent-ferroelectric-ca-hf-o2-and-sr-hf-o2-films-grown-from-chemical-solution-on-ito-coated-glass.pdf |
64a332ff9ea64cc167631919 | 10.26434/chemrxiv-2023-568ks | Double-bond delocalization in non-alternant hydrocarbons induces inverted singlet-triplet gaps | Molecules where the first excited singlet state is lower energy than the first excited triplet state have the potential to revolutionize OLEDs. This inverted singlet-triplet gap violates Hund’s rule and currently there are only a few molecules which are known to have this property. Here, we screen the complete set of non-alternant hydrocarbons consisting of 5-, 6-, 7-membered rings fused into two-, three- and four-ring polycyclic systems. We identify several molecules where the symmetry of the ground-state structure is broken due to bond-length alternation. Through symmetry-constrained optimizations we identify several molecular cores where the singlet-triplet gap is inverted when the structure is in a higher symmetry, pentalene being a known example. We uncover a strategy to stabilize the molecular cores into their higher-symmetry structures with electron donors or acceptors. We design several substituted pentalenes, s-indacenes, and indeno[1,2,3-ef]heptalenes with inverted gaps, among which there are several synthetically known examples. In contrast to known inverted gap emitters, we identify the double-bond delocalized structure of their conjugated cores as the necessary condition to achieve the inverted gap. This strategy enables chemical tuning and paves the way for the rational design of polycyclic hydrocarbons with inverted singlet-triplet gaps. These molecules are prospective emitters if their properties can be optimized for use in OLEDs. | Marc H. Garner; J. Terence Blaskovits; Clemence Corminboeuf | Theoretical and Computational Chemistry; Physical Chemistry; Computational Chemistry and Modeling; Photochemistry (Physical Chem.); Materials Chemistry | CC BY 4.0 | CHEMRXIV | 2023-07-04 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/64a332ff9ea64cc167631919/original/double-bond-delocalization-in-non-alternant-hydrocarbons-induces-inverted-singlet-triplet-gaps.pdf |
6635d03e91aefa6ce11edb61 | 10.26434/chemrxiv-2024-c94bp | Co3O4 (111) surfaces in contact with water: Molecular dynamics study of the surface chemistry and structure at room temperature | In this work, we have used ab initio molecular dynamics at room temperature to study the adsorption and dissociation of a thin water film on the Co3O4 (111) surfaces, considering the Co-rich and O-rich terminations known as the A-type and B-type surface terminations, respectively. We investigate the occupation of active sites, the hydrogen bond network at the interface and the structural response of the surfaces to water adsorption. On both terminations, water adsorbs via a partial dissociative mode. The contact layer is populated by molecular water as well as OH groups and surface OH resulting from proton transfer to the surface. The B-termination is more reactive, with a higher degree of dissociation in the contact layer with water (46%). On the B-terminated surface water barely adsorbs on the Co2+ sites and almost exclusively binds and dissociates on the Co3+ sites. The interaction with the surface consists mostly, of Co3+-Ow bonds and proton transfer exclusively to the 3-fold unsaturated surface Os1. Hydrogen bonds between water molecules in the aqueous film dominate the hydrogen bond network and no hydrogen bonds between water and the surface is observed. The A-terminated surface is less reactive. Water binds covalenlty on Co2+ sites, with a dissociation degree of 13% . Proton transfer occurs mostly on the 3-fold unsaturated surface oxygens Os1. Besides, short-lived surface OH arising from proton transfer to 3-fold unsaturated surface oxygens Os2 are observed. H-bonding to surface Os1 and Os2 constitute 12.7% and 19.8% of the H-bond network, respectively, and the largest contribution is found among the water molecules (67.4%). On both surfaces, the coordination number of the active sites drives the relaxations of the outermost atoms positions to the their bulk counterparts. The occupation of active sites on the B-termination could reach up to 3 adsorbates per Co3+ leading to a binding motif in which the Co is octahedrally coordinated and which was observed experimentally. | Tim Kox; Stephane Kenmoe | Theoretical and Computational Chemistry; Physical Chemistry; Catalysis; Computational Chemistry and Modeling; Heterogeneous Catalysis | CC BY NC ND 4.0 | CHEMRXIV | 2024-05-08 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/6635d03e91aefa6ce11edb61/original/co3o4-111-surfaces-in-contact-with-water-molecular-dynamics-study-of-the-surface-chemistry-and-structure-at-room-temperature.pdf |
60c73d50bdbb89fe70a37c5b | 10.26434/chemrxiv.5661736.v1 | Drug induced micellization into ultra-high capacity and stable curcumin nanoformulations: Comparing in vitro 2D and 3D-tumor model of triple-negative breast cancer | This manuscript describes a ultra-high loaded nanoformulation of curcumin. This compound is extremely water insoluble but could be dissolved using poly(2-oxazoline)/poly(2-oxazine) based polymer amphiphiles. The resulting formulations were thoroughly characterized in solution and solid form by NMR, dynamic light scattering, electron microscopy, HPLC zeta potential measurements, XRD, respectively. Biological activity was ensured and compared in 2D and 3D cell culture. | Michael M. Lübtow; Lena C. Nelke; Anna Brown; Gaurav Sahay; Gudrun Dandekar; Robert Luxenhofer | Drug delivery systems; Organic Polymers | CC BY NC ND 4.0 | CHEMRXIV | 2017-12-05 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/60c73d50bdbb89fe70a37c5b/original/drug-induced-micellization-into-ultra-high-capacity-and-stable-curcumin-nanoformulations-comparing-in-vitro-2d-and-3d-tumor-model-of-triple-negative-breast-cancer.pdf |
60c75119337d6c71cfe284b0 | 10.26434/chemrxiv.13118528.v1 | Bridged Bicyclic Building Block Upgrading: Photochemical Synthesis of bicyclo[3.1.1]heptan-1-Amines | Compounds containing bridged bicyclic carbon skeletons
are desirable building blocks for medicinal chemistry. However, as a result of
their inefficient, linear syntheses, commercially available compounds of this
sort are plagued by high costs and/or a lack of diversity in substitution
patterns. Herein we report the conversion of the readily available bicyclo[1.1.1]pentan-1-amine
substructure to a wide range of poly-substituted bicyclo[3.1.1]pentan-1-amines
using imine photochemistry. To our knowledge, this is the first reported method
to convert the bicyclo[1.1.1]pentane skeleton to the bicyclo[3.1.1]heptane
skeleton. Hydrolysis of the imine products gives complex, sp<sup>3</sup>-rich
primary amine building blocks. | Alexander Harmata; Madison Sowden; Corey Stephenson | Organic Synthesis and Reactions; Photochemistry (Org.) | CC BY NC ND 4.0 | CHEMRXIV | 2020-10-21 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/60c75119337d6c71cfe284b0/original/bridged-bicyclic-building-block-upgrading-photochemical-synthesis-of-bicyclo-3-1-1-heptan-1-amines.pdf |
633909b7e665bd0f621a189c | 10.26434/chemrxiv-2022-fvb7q-v2 | Magnetic Fields Enable Precise Spatial Control of Electrospun Fiber Alignment for Fabricating Complex Gradient Materials | Musculoskeletal interfacial tissues consist of complex gradients in structure, cell phenotype, and biochemical signaling that are important for function. Designing tissue engineering strategies to mimic these types of gradients is an ongoing challenge. In particular, new fabrication techniques that enable precise spatial control over fiber alignment are needed to better mimic the structural gradients present in interfacial tissues, such as the tendon-bone interface. Here, we report a modular approach to spatially controlling fiber alignment using magnetically-assisted electrospinning. Electrospun fibers were highly aligned in the presence of a magnetic field and smoothly transitioned to randomly aligned fibers away from the magnetic field. Importantly, magnetically-assisted electrospinning allows for spatial control over fiber alignment at sub-millimeter resolution along the length of the fibrous scaffold similar to the native structural gradient present in many interfacial tissues. The versatility of this approach was further demonstrated using multiple electrospinning polymers and different magnet configurations to fabricate complex fiber alignment gradients. As expected, cells seeded onto gradient fibrous scaffolds were elongated and aligned on the aligned fibers and did not show a preferential alignment on the randomly aligned fibers. Overall, this fabrication approach represents an important step forward in creating gradient fibrous materials, where such materials are promising as tissue-engineered scaffolds for regenerating functional musculoskeletal interfacial tissues. | R. Kevin Tindell; Lincoln Busselle; Julianne Holloway | Materials Science; Polymer Science; Biocompatible Materials; Fibers; Polymer scaffolds | CC BY NC ND 4.0 | CHEMRXIV | 2022-10-03 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/633909b7e665bd0f621a189c/original/magnetic-fields-enable-precise-spatial-control-of-electrospun-fiber-alignment-for-fabricating-complex-gradient-materials.pdf |
667f2e13c9c6a5c07ab4aa50 | 10.26434/chemrxiv-2024-dmfhw | Decarboxylative Cross-Coupling Enabled by Fe and Ni Metallaphotoredox Catalysis | Decarboxylative cross-coupling of carboxylic acids and aryl halides has become a key transformation in organic synthe- sis to form C(sp2)–C(sp3) bonds. In this report, a base metal pairing between Fe and Ni has been developed with complementary reactivity to the well-established Ir and Ni metallaphotoredox reactions. Utilizing an inexpensive FeCl3 co-catalyst along with a pyr- idine carboxamidine Ni catalyst, a range of aryl iodides can be preferentially coupled to carboxylic acids over boronic acid esters, triflates, chlorides, and even bromides in high yields. Additionally, carboxylic acid derivatives containing heterocycles, N-protected amino acids, electron-rich amines, and protic functionality can be coupled in 23-96% yield with a range of sterically hindered, elec- tron-rich, and electron-deficient aryl iodides. Preliminary catalytic and stoichiometric reactions support a mechanism in which Fe is responsible for the activation of carboxylic acid upon irradiation with light and a Ni(I)alkyl intermediate is responsible for activation of the aryl iodide coupling partner followed by reductive elimination to generate product. | Reem Nsouli; Sneha Nayak; Venkadesh Balakrishnan; Jung-Ying Lin; Benjamin K Chi; Hannah G. Ford; Andrew Tran; Ilia A. Guzei; John Bacsa; Nicholas Armada; Fedor Zenov; Daniel J. Weix; Laura K.G. Ackerman-Biegasiewicz | Organic Chemistry; Catalysis; Organometallic Chemistry; Organic Synthesis and Reactions; Homogeneous Catalysis; Photocatalysis | CC BY NC ND 4.0 | CHEMRXIV | 2024-07-01 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/667f2e13c9c6a5c07ab4aa50/original/decarboxylative-cross-coupling-enabled-by-fe-and-ni-metallaphotoredox-catalysis.pdf |
64e8da3879853bbd786ca4eb | 10.26434/chemrxiv-2023-lw5k0 | Uni-pKa: An Accurate and Physically Consistent pKa
Prediction through Protonation Ensemble Modeling | Predicting pKa values of small molecules has key applications in drug discovery and molecular simulation. However, current methods face challenges in rigorously interpreting experimental data and ensuring thermodynamic consistency between successive pKa values. This study puts forward a protonation ensemble framework to address these limitations by modeling the full space of possible protonation microstates. Within this framework, we derive rigorous definitions connecting experimental macro-pKas to underlying micro-pKa equilibria. Under this new framework, we develop Uni-pKa, an accurate and reliable pKa predictor. Uni-pKa first pretrains on over 1 million predicted pKas from ChemBL to learn expressive molecular representations. It is then finetuned on experimental datasets that enforce consistency with the protonation ensemble definitions. The high-quality experimental pKa datasets are fitted to this framework by recovering underlying microstates from macro-pKas. Modeling the complete ensemble enables rigorous interpretation of macro-pKa data, and inherently preserves thermodynamic consistency, improving the prediction accuracy of Uni-pKa. Experiments demonstrate that Uni-pKa achieves state-of-the-art performance, outperforming previous methods. This novel protonation ensemble approach significantly advances machine learning for pKa prediction and molecular property modeling. Uni-pKa provides a good example of how to combine chemical knowledge and machine learning methods. Users can utilize Uni-pKa for predicting and ranking the protonation states of molecules under various pH conditions via https://app.bohrium.dp.tech/uni-pka. | Weiliang Luo; Gengmo Zhou; Zhengdan Zhu; Guolin Ke; Zhewei Wei; Zhifeng Gao; Hang Zheng | Theoretical and Computational Chemistry; Physical Chemistry; Analytical Chemistry; Chemoinformatics; Machine Learning; Thermodynamics (Physical Chem.) | CC BY NC ND 4.0 | CHEMRXIV | 2023-08-28 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/64e8da3879853bbd786ca4eb/original/uni-p-ka-an-accurate-and-physically-consistent-p-ka-prediction-through-protonation-ensemble-modeling.pdf |
60c74cd3bb8c1a32723db4b0 | 10.26434/chemrxiv.12548003.v1 | Computational Design of Potent Inhibitors for SARS-CoV-2’s Main Protease | In silico drug design can play a vital role in identifying promising drug candidates against COVID-19. Herein, we focused on the main protease of SARS-CoV-2 that plays crucial biological functions in the virus. We performed a ligand-based virtual screening followed by a docking screening for testing approved drugs and bioactive compounds listed in the DrugBank and ChEMBL databases. The top 8 docking results were advanced to all-atom MD simulations to study the relative stability of the protein-ligand interactions.Our results suggest several promising approved and bioactive inhibitors of SARS-CoV-2 Mpro. | Abd Al-Aziz A. Abu-Saleh; Ibrahim Awad; Arpita Yadav; Raymond A. Poirier | Computational Chemistry and Modeling | CC BY NC ND 4.0 | CHEMRXIV | 2020-06-25 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/60c74cd3bb8c1a32723db4b0/original/computational-design-of-potent-inhibitors-for-sars-co-v-2-s-main-protease.pdf |
60c73d51469df43555f426d3 | 10.26434/chemrxiv.5746197.v1 | Plasmonic Glasses and Films Based on Alternative Inexpensive Materials for Blocking Infrared Radiation | The need for energy-saving materials is pressing. This paper reports on
the design of energy-saving glasses and films based on plasmonic
composite glasses is nontrivial and requires to take full advantage of
both materials and shape-related properties of the nanoparticles. We
compute the performance of solar plasmonic glasses incorporating a
transparent matrix and specially-shaped nanocrystals. Plasmonic
nanoshells are shown to exhibit the best performances as compared to
nanorods and nanocups. Simultaneously, the synthesis of plasmonic
nanoshells is technologically feasible using gas-phase fabrication
methods. The computational work was done for noble metals (Au, Ag) as
well as for alternative plasmonic materials (Al, Cu, TiN). Inexpensive
materials (Ag, Al, Cu, TiN) show overall good performance in terms of
the commonly-used figures of merit of industrial glass windows. Together
with numerical data for specific materials, this study includes a set
of general rules for designing efficient plasmonic IR-blocking media.
The plasmonic glasses proposed herein are good candidates for cheap
optical media to be used in energy-saving windows in warm climates'
housing or temperature-sensitive infrastructure. | Lucas Vazquez Besteiro; Xiang-Tian Kong; Zhiming Wang; Federico Rosei; Alexander Govorov | Core-Shell Materials; Metamaterials; Optical Materials; Nanostructured Materials - Nanoscience | CC BY NC ND 4.0 | CHEMRXIV | 1970-01-01 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/60c73d51469df43555f426d3/original/plasmonic-glasses-and-films-based-on-alternative-inexpensive-materials-for-blocking-infrared-radiation.pdf |
60c74330ee301c4ddcc78f62 | 10.26434/chemrxiv.8967944.v1 | Structural Characterization of Agonist Binding to A3 Adenosine Receptor through Biomolecular Simulations and Mutagenesis Experiments | <div>The study aimed at highlighting
features of the still-unsolved A<sub>3</sub>R that
are important for IB-MECA and NECA binding and may be used for the design of
effective ligands using computational and mutagenesis studies.<br /></div> | Dimitrios Stamatis; Panagiotis Lagarias; Kerry Barkan; Eleni Vrontaki; Graham Ladds; Antonios Kolocouris | Biochemistry; Bioinformatics and Computational Biology; Chemical Biology | CC BY NC ND 4.0 | CHEMRXIV | 2019-07-22 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/60c74330ee301c4ddcc78f62/original/structural-characterization-of-agonist-binding-to-a3-adenosine-receptor-through-biomolecular-simulations-and-mutagenesis-experiments.pdf |
66da021612ff75c3a183c262 | 10.26434/chemrxiv-2024-5vwkp-v2 | Green Synthesis of Morpholines via Selective Monoalkylation of Amines | Morpholines are common heterocycles in pharmaceutical and agricultural products, yet methods to synthesize them from 1,2-amino alcohols are inefficient. We report the simple, high yielding, one or two-step, redox neutral protocol using inexpensive reagents (ethylene sulfate and tBuOK) for the conversion of 1,2-amino alcohols to morpholines. Key to this methodology is the identification of general conditions that allow for the clean isolation of monoalkylation products derived from a simple SN2 reaction between an amine and ethylene sulfate. Experiments suggest that the degree of selectivity is dependent upon the structure of reacting 1,2-amino alcohol as well as the unique properties of ethylene sulfate. This method can be used for the synthesis of a variety of morpholines containing substituents at various positions, including 28 examples derived from primary amines and multiple examples contained in known active pharmaceutical ingredients. We have conducted multiple examples on >50 g scale. We have also demonstrated the formal synthesis of a morpholine from a simple primary amine using ethylene sulfate. Overall, while this new methodology has many environmental and safety benefits relative to the traditional methods used to prepare morpholines from 1,2-amino alcohols the most striking feature is the facile selective monoalkylation of a variety of primary amines. We have also explored various reactions beyond those related to the synthesis of morpholines, including obtaining proof-of-principle that ethylene sulfate can be used for the synthesis of piperazines and as a 2-carbon electrophile for fragment couplings. | Kacey Ortiz; Andrew Brusoe; Jason An; Eugene Chong; Lifen Wu | Organic Chemistry; Organic Synthesis and Reactions; Process Chemistry | CC BY NC ND 4.0 | CHEMRXIV | 2024-09-06 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/66da021612ff75c3a183c262/original/green-synthesis-of-morpholines-via-selective-monoalkylation-of-amines.pdf |
61f0407b8d70c347850dac4f | 10.26434/chemrxiv-2022-hvh6b | BTDAzo - a photoswitchable TRPC5 channel activator | Photoswitchable reagents to modulate protein activity are powerful tools for high-spatiotemporal-precision control over endogenous biological functions. TRPC5 is a Ca2+-permeable cation channel with distinct tissue-specific roles, ranging from synaptic function to hormone regulation. Achieving spatially-resolved control over TRPC5 activity in particular cells or tissues, and temporal regulation in targeted cells, are therefore crucial milestones towards understanding and harnessing the biology of TRPC5. Here we develop the first photoswitchable TRPC5-modulating reagent, BTDAzo, towards reaching this goal. BTDAzo can photocontrol TRPC5 currents in cell culture, as well as controlling endogenous TRPC5-based neuronal Ca2+ responses in mouse brain slices. BTDAzos are also the first reported azo-benzothiadiazines, an accessible and conveniently derivatised azoheteroarene that features excellent two-colour photoswitching. BTDAzo's TRPC5 control across relevant channel biology settings makes it appropriate for a range of dynamically reversible photoswitching studies in TRP channel biology, aiming to decipher the various biological roles of this centrally important ion channel. | Markus Müller; Konstantin Niemeyer; Nicole Urban; Navin K. Ojha; Frank Zufall; Trese Leinders-Zufall; Michael Schaefer; Oliver Thorn-Seshold | Biological and Medicinal Chemistry; Organic Chemistry; Bioorganic Chemistry; Photochemistry (Org.); Chemical Biology | CC BY NC 4.0 | CHEMRXIV | 2022-01-28 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/61f0407b8d70c347850dac4f/original/btd-azo-a-photoswitchable-trpc5-channel-activator.pdf |
60c74a9bee301c1838c79c8f | 10.26434/chemrxiv.12229202.v1 | Single-Molecule Junction Origami | Stimuli-responsive
molecular junctions, where the conductance can be altered by an external
perturbation, are an important class of nanoelectronic devices. These have
recently attracted interest as large effects can be introduced through
exploitation of quantum phenomena. We show here that significant changes in conductance
can be attained as a molecule is repeatedly compressed and relaxed, resulting
in molecular folding along a flexible fragment and cycling between an <i>anti</i>
and a <i>syn </i>conformation. Power spectral density analysis and DFT
transport calculations show that through-space tunnelling between two phenyl
fragments is responsible for the conductance increase as the molecule is
mechanically folded to the <i>syn</i> conformation. This phenomenon represents
a novel class of mechanoresistive molecular devices, where the functional
moiety is embedded in the conductive backbone and exploits intramolecular
nonbonding interactions, in contrast to most studies where mechanoresistivity
arises from changes in the molecule-electrode interface. | Chuanli Wu; Demetris Bates; Sara Sangtarash; Nicolò Ferri; Aidan Thomas; Simon Higgins; Craig M. Robertson; Richard Nichols; Hatef Sadeghi; Andrea Vezzoli | Nanodevices | CC BY NC ND 4.0 | CHEMRXIV | 2020-05-05 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/60c74a9bee301c1838c79c8f/original/single-molecule-junction-origami.pdf |
6491e9caa2c387fa9aa5e4cd | 10.26434/chemrxiv-2023-392pg-v2 | A process-level perspective of the impact of molecular force fields on the computational screening of MOFs for carbon capture | The question we pose in this study is to what extent the ranking of metal organic frameworks (MOFs) for adsorption-based carbon capture, and the selection of top performers identified in Pressure Swing Adsorption (PSA) process modelling, depends on the choice of the commonly available forcefields. To answer this question, we first generated distributions of CO2 and N2 adsorption isotherms via molecular simulation in 690 MOFs using six typical forcefields: the UFF or Dreiding sets of Lennard-Jones parameters, in combination with partial charges derived from ab initio calculations or by charge equilibration schemes. We then conducted a systematic uncertainty quantification study using PSA process-level modelling. We observe that: (i) the ranking of MOFs significantly depends on the choice of forcefield; (ii) partial charge assignment is the prevailing source of uncertainty, and that charge equilibration schemes produce results which are inconsistent with ab initio-derived charges; iii) the choice of Lennard-Jones parameters is a considerable source of uncertainty. Our work highlights that is not really possible to obtain material rankings with high resolution using a single molecular modelling approach and that, as a minimum, some uncertainty should be estimated for the performance of MOFs shortlisted using high throughput computational screening workflows. Future prospects for computational screening studies are also discussed. | Conor Cleeton; Felipe Lopes de Oliveira; Rodrigo Neumann; Amir Farmahini ; Binquan Luan ; Mathias Steiner ; Lev Sarkisov | Chemical Engineering and Industrial Chemistry; Materials Chemistry | CC BY 4.0 | CHEMRXIV | 2023-06-21 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/6491e9caa2c387fa9aa5e4cd/original/a-process-level-perspective-of-the-impact-of-molecular-force-fields-on-the-computational-screening-of-mo-fs-for-carbon-capture.pdf |
60c758d50f50db34bd398510 | 10.26434/chemrxiv.14386547.v2 | Area Selective Deposition of Iron Films Using Temperature Sensitive Masking Materials and Plasma Electrons as Reducing Agents | <p>potential of area selective deposition (ASD) with a newly developed chemical vapor deposition method, which utilize plasma electrons as reducing agents for deposition of metal-containing films, is demonstrated using temperature sensitive polymer-based masking materials. The masking materials tested were polydimethylsiloxane (PDMS), polymethylmethacrylate (PMMA), polystyrene (PS), parafilm, Kapton tape, Scotch tape, and office paper. The masking materials were all shown to prevent film growth on the masked area of the substrate without being affected by the film deposition process. X-ray photoelectron spectroscopy analysis confirms that the films deposited consist mainly of iron, whereas no film material is found on the masked areas after mask removal. SEM analysis of films deposited with non-adhesive masking materials show that film growth extended for a small distance underneath the masking material, indicating that the CVD process with plasma electrons as reducing agents is not a line-of-sight deposition technique. The reported methodology introduces an inexpensive and straightforward approach for ASD that opens for exciting new possibilities for robust and less complex area selective metal-on-metal deposition. </p> | Hama Nadhom; Yusheng Yuan; Polla Rouf; Niclas Solin; Henrik Pedersen | Coating Materials; Materials Processing; Thin Films; Interfaces; Surface | CC BY NC ND 4.0 | CHEMRXIV | 2021-05-11 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/60c758d50f50db34bd398510/original/area-selective-deposition-of-iron-films-using-temperature-sensitive-masking-materials-and-plasma-electrons-as-reducing-agents.pdf |
652521d5bda59ceb9a4026e8 | 10.26434/chemrxiv-2023-4l672 | Bis(pinacolato)diboron-Enabled Ni-Catalyzed Reductive Coupling of Alkyl with Aryl/Vinyl Electrophiles | The chemistry herein stresses the use of economic and environmentally friendly (bispinacolato)diboron, as the non-metallic reductant that enables the reductive cross-coupling of alkyl electrophiles with aryl/vinyl halides to afford C(sp3)–C(sp2) bond forming products. The present method displays equivalent coupling efficiencies to those reported ones using Zn and Mn as the terminal reductants that have predominated the field of cross-electrophile coupling. Our mechanistic studies support that B2Pin2-mediated reduction of NiII to Ni0, and a radical-chain process emphasizing interception of an alkyl Ni(0) may operate to give alkyl–NiI followed by oxidative addition of ArX to give a key alkyl–NiIII–Ar intermediate prior to ejection of the product. We believe the present study offers insight into the use of B2Pin2 as a non-metallic reductant that does not involve a SET reduction process. | Deli Sun; Yuxin Gong; Yunrong Chen; Hegui Gong | Organic Chemistry; Organic Synthesis and Reactions | CC BY NC ND 4.0 | CHEMRXIV | 2023-10-11 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/652521d5bda59ceb9a4026e8/original/bis-pinacolato-diboron-enabled-ni-catalyzed-reductive-coupling-of-alkyl-with-aryl-vinyl-electrophiles.pdf |
64e2a7ad694bf1540cb21fd0 | 10.26434/chemrxiv-2023-t2q5h-v2 | Data-driven imputation of miscibility of aqueous solutions via graph-regularized logistic matrix factorization | Aqueous, two-phase systems (ATPSs) may form upon mixing two solutions of independently water-soluble compounds. Many separation, purification, and extraction processes rely on ATPSs. Predicting the miscibility of solutions can accelerate and reduce the cost of the discovery of new ATPSs for these applications. Whereas previous machine learning approaches to ATPS prediction used physicochemical properties of each solute as a descriptor, in this work, we show how to impute missing miscibility outcomes directly from an incomplete collection of pairwise miscibility experiments. We use graph-regularized logistic matrix factorization (GR-LMF) to learn a latent vector of each solution from (i) the observed entries in the pairwise miscibility matrix and (ii) a graph (nodes: solutes, edges: shared relationships) indicating the general category of the solute (i.e., polymer, surfactant, salt, protein). For an experimental dataset of the pairwise miscibility of 68 solutions from Peacock et al. [ACS Appl. Mater. Interfaces 2021, 13, 11449--11460], we find that GR-LMF more accurately predicts missing (im)miscibility outcomes of pairs of solutions than ordinary logistic matrix factorization and random forest classifiers that use physicochemical features of the solutes. GR-LMF obviates the need for features of the solutions/solutes to impute missing miscibility outcomes, but it cannot predict the miscibility of a new solution without some observations of its miscibility with other solutions in the training data set. | Diba Behnoudfar; Cory Simon; Joshua Schrier | Theoretical and Computational Chemistry; Physical Chemistry; Chemical Engineering and Industrial Chemistry; Machine Learning; Solution Chemistry | CC BY NC ND 4.0 | CHEMRXIV | 2023-08-21 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/64e2a7ad694bf1540cb21fd0/original/data-driven-imputation-of-miscibility-of-aqueous-solutions-via-graph-regularized-logistic-matrix-factorization.pdf |
60c75697337d6c4b77e28e5b | 10.26434/chemrxiv.14084201.v1 | Rheological Behavior of Polymer Nanocomposites Filled with Spherical Nanoparticles: Insights from Molecular Dynamics Simulation | <div><div>It is very urgent to understand the rheological behavior of polymer nanocomposites (PNCs) on the molecular level, which is very important for their processing and application. Thus, here the reverse nonequilibrium molecular dynamics simulation isemployed to explore it by tuning the nanoparticle (NP) concentration, the polymer-NPinteraction and the NP size. The shear viscosity (η~-m) exhibits a power law with theshear rate where m varies from 0.42 to 0.53 at high shear rates. By adopting the Carreau-Yasuda model, the obtained zero-shear viscosity gradually rises with increasing the NPconcentration, polymer-NP interaction or reducing the NP size. This is attributed to thestrong adsorption of chains by NPs and the formed network, which leads to the retarded dynamics. In addition, both the first and second normal stress differences also show power laws on the shear rates. The chains are gradually extended as the increase of shear rates, which is characterized by the mean-square end-to-end distance and the mean square radius of gyration. Especially, the evolution process of the NP network and the polymer- NP network is analyzed to deeply understand the shear thinning behavior. The number ofthe direct contact structure of NPs increases while the number of polymer-NP bridgedstructure is reduced. This is further proved by the increase of the formation probability of the NP network and the decrease of the polymer-NP interaction energy. Finally, the chain dynamics is found to be enhanced due to the shear flow. In summary, this work provides a further understanding on the mechanism of the shear thinning of PNCs on the molecular level. <br /></div></div> | Haoxiang Li; Haoyu WU; Wenfeng Zhang; Xiuying Zhao; Yangyang Gao; Liqun Zhang | Composites | CC BY NC ND 4.0 | CHEMRXIV | 2021-03-24 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/60c75697337d6c4b77e28e5b/original/rheological-behavior-of-polymer-nanocomposites-filled-with-spherical-nanoparticles-insights-from-molecular-dynamics-simulation.pdf |
64ca90044a3f7d0c0d7bbbc2 | 10.26434/chemrxiv-2023-knn1v | Active Learning of Neural Network Potentials for Rare Events | Atomistic simulation with machine learning-based potentials (MLPs) is an emerging tool for understanding materials' properties and behaviors and predicting novel materials. Neural network potentials (NNPs) are outstanding in this field as they have shown a comparable accuracy to ab initio electronic structure calculations for reproducing potential energy surfaces while being several orders of magnitude faster. However, such NNPs can perform poorly outside their training domain and often fail catastrophically in predicting rare events in molecular dynamics (MD) simulations. The rare events in atomistic modeling typically include chemical bond breaking/formation, phase transitions, and materials failure, which are critical for new materials design, synthesis, and manufacturing processes. In this study, we develop an automated active learning (AL) capability by combining NNPs and enhanced sampling methods for capturing rare events to derive NNPs for targeted applications. We develop a decision engine based on configurational similarity and uncertainty quantification (UQ), using data augmentation for effective AL loops to distinguish the informative data from enhanced sampled configurations, showing that the generated data set achieves an activation energy error of less than 1 kcal/mol. Furthermore, we have devised a strategy to alleviate training uncertainty within AL iterations through a carefully constructed data selection process that leverages an ensemble approach. Our study provides essential insight into the relationship between data and the performance of NNP for the rare event of bond breaking under mechanical loading. It highlights strategies for developing NNPs of broader materials and applications through active learning. | Gang Seob Jung; Jong Youl Choi; Sangkeun Lee | Theoretical and Computational Chemistry; Materials Science; Catalysis; Machine Learning | CC BY NC 4.0 | CHEMRXIV | 2023-08-14 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/64ca90044a3f7d0c0d7bbbc2/original/active-learning-of-neural-network-potentials-for-rare-events.pdf |
60c743b6f96a003588286871 | 10.26434/chemrxiv.7957544.v2 | Structure-Reactivity Relationships on Substrates and Inhibitors of the Lysine Deacylase Sirtuin 2 from Schistosoma Mansoni (SmSirt2) | The only drug for treatment of Schistosomiasis is Praziquantel, and the possible emergence of resistance makes research on novel therapeutic agents necessary. Targeting of Schistosoma mansoni epigenetic enzymes, which regulate the parasitic life cycle, emerged as promising approach. Due to the strong effects of human Sirtuin inhibitors on parasite survival and reproduction, Schistosoma sirtuins were postulated as therapeutic targets. In vitro testing of synthetic substrates of S. mansoni Sirtuin 2 (SmSirt2) and kinetic experiments on a myristoylated peptide demonstrated lysine long chain deacylation as an intrinsic SmSirt2 activity for the first time. Focused in vitro screening of the GSK Kinetobox library and structure-activity relationships (SAR) of identified hits, led to the first SmSirt2 inhibitors with activity in the low micromolar range. Several SmSirt2 inhibitors showed potency against both larval schistosomes (viability) and adult worms (pairing, egg laying) in culture without general toxicity to human cancer cells.<br /> | Daria Monaldi; Dante Rotili; Julien Lancelot; Martin Marek; Nathalie Wössner; Alessia Lucidi; Daniela Tomaselli; Elizabeth Ramos-Morales; Christophe Romier; Raymond
J. Pierce; Antonello Mai; Manfred Jung | Biochemistry; Chemical Biology; Drug Discovery and Drug Delivery Systems; Microbiology | CC BY NC ND 4.0 | CHEMRXIV | 2019-08-02 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/60c743b6f96a003588286871/original/structure-reactivity-relationships-on-substrates-and-inhibitors-of-the-lysine-deacylase-sirtuin-2-from-schistosoma-mansoni-sm-sirt2.pdf |
677a05d481d2151a02e9dec1 | 10.26434/chemrxiv-2025-kh927 | Assembly of Functionalized Organic Fragments via Reductive Activation and (Cross)-Coupling of C2H4, CO, CO2 and/or H2 using a Magnesium-Dinitrogen Complex | Reactions of 1,2-dimagnesioethane compound [{K(TCHPNON)Mg}2(-C2H4)] (TCHPNON = 4,5-bis(2,4,6-tricyclohexylanilido)-2,7-diethyl-9,9-dimethyl-xanthene), formed by the two-electron reduction of ethene with a dimagnesium/dipotassium complex of reduced N2, viz. [{K(TCHPNON)Mg}2(-N2)], with CO and CO2 have been explored. In the case of the reaction with CO, cross-coupling of the reduced ethene fragment with two molecules of CO gave a heterobimetallic complex of the parent cyclobutenediolate dianion, [{K(TCHPNON)Mg}2(-O2C4H4)], which when exposed to THF gave adduct [{K(TCHPNON)Mg}2(-O2C4H4)(THF)]. Treating [{K(TCHPNON)Mg}2(-C2H4)] with CO2 led to insertion of CO2 into both Mg‒C bonds and all Mg‒N bonds of the 1,2-dimagnesioethane species, yielding a magnesium succinate complex, [{K(TCHPNON-C2O4)Mg}2(-O4C4H4)], in which the diamide ligands of the starting material have been converted to xanthene bridged dicarbamates. The reactions can be viewed as involving the “masked-magnesium(I)” induced cross-coupling of ethene with either CO or CO2, to give more complex organic products. Reaction of [{K(TCHPNON)Mg}2(-N2)] with CO2, proceeded via reductive coupling of the heterocumulene to give the oxalate dianion, in addition to insertion of CO2 into all Mg‒N bonds of the magnesium-dinitrogen complex, forming dimeric [{K(TCHPNON-C2O4)Mg}2(-O4C2)]2. When treated with THF this dissociates to monomeric [{K(THF)(TCHPNON-C2O4)Mg(THF)}2(-O4C2)]. Related chemistry results from the reaction of a dianionic magnesium(I) compound with CO2. In contrast, C‒C bond formation was not observed in the reaction of [{K(TCHPNON)Mg}2(-N2)] with a CO2 analogue, i.e. the carbodiimide CyNCNCy (Cy = cyclohexyl). Instead, H abstraction by a proposed intermediate containing a reduced carbodiimide radical fragment, gave polymeric formamidinate complex [K(TCHPNON)Mg{(CyN)2CH}]∞. Reaction of CO2 with the magnesium hydride complex [{K(TCHPNON)Mg(-H)}2] (formed by activation of H2 with [{K(TCHPNON)Mg}2(-N2)]), gave the unusual trimeric magnesium formate complex [{K(TCHPNON-CO2)Mg}(-O2CH)]3 in which CO2 has inserted into only one Mg‒N bond of each TCHPNON ligand. All of the above-mentioned reactions reveal the capacity of [{K(TCHPNON)Mg}2(-N2)] to act as a masked dimagnesium(I) diradical in reductive coupling or cross-coupling of the simple gaseous reagents, C2H4, CO, CO2 and H2, to give value-added organic fragments. | Dat T. Nguyen; Rahul Mondal; Matthew J. Evans; Joseph M. Parr; Cameron Jones | Inorganic Chemistry; Organometallic Chemistry; Main Group Chemistry (Organomet.); Small Molecule Activation (Organomet.) | CC BY NC ND 4.0 | CHEMRXIV | 2025-01-07 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/677a05d481d2151a02e9dec1/original/assembly-of-functionalized-organic-fragments-via-reductive-activation-and-cross-coupling-of-c2h4-co-co2-and-or-h2-using-a-magnesium-dinitrogen-complex.pdf |
650ef57ab927619fe7acea3e | 10.26434/chemrxiv-2023-vj5n0 | Nonlinear potentiodynamic battery charging protocols for fun, education, and application | Most secondary batteries in academia are (dis)charged by applying a constant current (CC) followed by a constant voltage (CV) i.e. a CCCV procedure. The usual concept is then to condense data for interpretation into representations such as differential capacity, or dQ/dV, graphs. This is done to extract information related to phenomena such as the growth of the solid electrolyte interphase (SEI) or, more broadly, degradation. Typically, these measurements take several months because measurements for differential capacity analysis need to be performed at relatively low C-rates. An alternate charging schedule to CCCV is pulsed charging, where CC sections are interrupted by an open-circuit measurement on the second time scale. These and similar partially constant current strategies primarily target diffusive effects during charging and broadly fall into a linear charging category, where the time derivative for the actuated property is mostly zero. Herein, I explore nonlinear charging i.e., the process of actively applying a potential with a nontrivial time derivate and a resulting non-trivial current time derivative to engineer (dis)charge cycles with enhanced information density. This method of nonlinear charging is then used to charge a cell such that some potential ranges in the differential capacity diagram are omitted. This study is purely a simulative endeavor and not backed by experimentation, owing mainly to the lack of facile implementation of arbitrary function inputs for battery cyclers and might point to limitations of the underlying theory. If found to be confirmed through an experiment, this technique would, however motivate a new roadmap to better understand secondary battery degradation inspired by electrocatalyst degradation. | Helge Sören Stein | Physical Chemistry; Analytical Chemistry; Energy; Electrochemical Analysis; Electrochemistry - Mechanisms, Theory & Study | CC BY 4.0 | CHEMRXIV | 2023-09-25 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/650ef57ab927619fe7acea3e/original/nonlinear-potentiodynamic-battery-charging-protocols-for-fun-education-and-application.pdf |
671102a112ff75c3a1b1d3d9 | 10.26434/chemrxiv-2024-8vb2n-v2 | Exposing the role of pre-association in interfacial proton-coupled electron transfer | Interfacial proton-coupled electron transfer (I-PCET) reactions are typically viewed as single elementary reaction steps even though analogous solution-phase reactivity is known to require pre-association of proton donor and acceptor. Herein, we examine the role of pre-association in I-PCET to a molecularly well-defined graphite-conjugated carboxylic acid (GC-COOH) surface site. We quantify electrolyte proton activity and I PCET kinetics in acidic, acetate buffered, and alkaline electrolytes as a function of NaClO4 concentration, ranging from 1 mole kg−1 to 17 mole kg−1. Upon accounting for the previously measured proton activity dependence of I-PCET kinetics to GC-COOH, we find that rate of I-PCET is systematically attenuated by factors of 4.3 and 4.6 over this range of NaClO4 concentration in acidic and acetate buffered media, respectively. In contrast, the rate of I-PCET remains unchanged within error across NaClO4 concentration in alkaline electrolyte. Based on these observations, we propose a multiple-step model for I-PCET in acidic media that invokes quasi-equilibrated displacement of Na+ from the interface to form hydrogen-bonded pre-association complexes prior to rate-limiting concerted proton-electron transfer. Increased NaClO4 concentration is invoked to increase Na+ activity in the bulk vs the interface, inhibiting pre-association complex formation and the overall I-PCET rate. These studies emphasize the non-innocent role of support electrolyte species and expose the key role of pre-association equilibria in I-PCET mechanisms. The work also suggests that control over pre-association equilibria could be used as an additional handle for tailoring the kinetics of interfacial ion transfer reactions. | Noah B. Lewis; Joel G. Gardner ; Neil K. Razdan; Shane Ardo; Yogesh Surendranath | Inorganic Chemistry; Electrochemistry | CC BY NC ND 4.0 | CHEMRXIV | 2024-10-18 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/671102a112ff75c3a1b1d3d9/original/exposing-the-role-of-pre-association-in-interfacial-proton-coupled-electron-transfer.pdf |
6655cc6d21291e5d1d77862d | 10.26434/chemrxiv-2024-5dkhm | Implementation of an Open Chemistry Knowledge Base with a Semantic Wiki | In this work, a concept for an open chemistry knowledge base was developed to integrate chemical research results into a collaboratively usable platform. To achieve this, we enhanced Semantic MediaWiki (SMW) to support the collection and structured summary of chemical data contained in publications. We implemented tools for capturing chemical structures in machine-readable formats and designed data forms along with a data model to ensure standardized input and organization of research results. These enhancements allow for effective data comparison and contextual analysis within an expandable Wiki environment. The use of the platform was specifically demonstrated by organizing and comparing research in the area of “CO2 reduction in homogeneous photocatalytic systems,” showcasing its potential to significantly enhance the collaborative collection of research outcomes. | Charlotte Neidiger; Tarek Saier; Kai Kühn; Victor Larignon; Michael Färber; Claudia Bizzarri ; Helena Šimek Tosino; Laura Holzhauer; Michael Erdmann; An Nguyen; Dean Harvey; Pierre Tremouilhac; Claudia Kramer; Daniel Hansch; Nicole Jung; Stefan Bräse | Organic Chemistry; Catalysis; Chemical Education; Organic Synthesis and Reactions; Photocatalysis; Redox Catalysis | CC BY 4.0 | CHEMRXIV | 2024-05-31 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/6655cc6d21291e5d1d77862d/original/implementation-of-an-open-chemistry-knowledge-base-with-a-semantic-wiki.pdf |
Subsets and Splits
No saved queries yet
Save your SQL queries to embed, download, and access them later. Queries will appear here once saved.