ChemRxiv : the preprint server for chemistry最新文献

{"title":"Enhancing the Throughput of FT Mass Spectrometry Imaging Using Compressed Sensing and Subspace Modeling","authors":"Yuxuan Richard Xie, Daniel Coelho de Castro, S. Rubakhin, J. Sweedler, F. Lam","doi":"10.33774/chemrxiv-2021-ks1vf","DOIUrl":"https://doi.org/10.33774/chemrxiv-2021-ks1vf","url":null,"abstract":"Mass spectrometry imaging (MSI) allows for untargeted mapping of the chemical compositions of tissues with attomole detection limits. MSI using Fourier transform-based mass spectrometers, such as FT-ion cyclotron resonance (FT-ICR), grants the ability to examine the chemical space with unmatched mass resolution and mass accuracy. However, direct imaging of large tissue samples on FT-ICR is restrictively slow. In this work, we present an approach that combines the subspace modeling of ICR temporal signals with compressed sensing to accelerate high-resolution FT-ICR MSI. A joint subspace and sparsity constrained reconstruction enables the creation of high-resolution imaging data from the sparsely sampled and short-time acquired transients. Simulation studies and experimental implementation of the proposed acquisition in investigation of brain tissues demonstrate a factor of 10 enhancement in throughput of FT-ICR MSI, without the need for instrumental or hardware modifications.","PeriodicalId":72565,"journal":{"name":"ChemRxiv : the preprint server for chemistry","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2021-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"49545446","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Efficient Dynamic Computational Strategy for Heterogeneous Catalysis Based on Neural Network Potential Energy Surface: A Case Study of Temperature-Dependent Thermodynamics and Kinetics for the Chemisorbed on-surface CO","authors":"Jun Chen, Tan Jin, Tonghao Shen, Mingjun Yang, Zhe-ning Chen","doi":"10.33774/chemrxiv-2021-jpk9v","DOIUrl":"https://doi.org/10.33774/chemrxiv-2021-jpk9v","url":null,"abstract":"As a favorable alternative and complement of experimental techniques, computational tools on top of ab initio calculations have played an indispensable role in revealing the molecular details, thermodynamics and kinetics in catalytic reactions. The static computational strategy, which recovers the reaction thermodynamics and kinetics based on the calculations of a few stationary geometries at zero temperature and some ideal statistic mechanics models, is the most popular approach in theoretical catalysis due to its simplicity. In comparison, the ab initio molecular dynamics (AIMD) is a well-tested approach to provide more precise descriptions of catalytic processes, however, experiencing a significantly expensive computational cost in the direct ab initio calculation of potential energy and gradients. Here we proposed a highly efficient dynamic computational strategy for the calculation of thermodynamic and kinetic properties in heterogeneous catalysis on the basis of neural network potential energy surface (NN PES) and MD simulations. Taking CO adsorbate on Ru(0001) surface as the illustrative model catalytic system, we demonstrated that our NN-PES-based MD simulations can efficiently generate the reliable smooth two-dimensional potential-of-mean-force (2-D PMF) surfaces in a wide range of temperatures (from 300 to 900 K), and thus temperature-dependent thermodynamic properties can be obtained in a comprehensive investigation on the whole PMF surface rather than a rough estimation using ideal models based on a few optimized geometries. Moreover, MD simulations offer an effective way to describe the surface kinetics such as the CO adsorbate on-surface movement, which goes beyond the most popular static estimation based on calculated free energy barrier and transition state theory (TST). By comparing the results obtained in the dynamic and static approaches, we further revealed that the dynamic strategy significantly improves the predictions of both thermodynamic and kinetic properties as compared to the popular ideal statistic mechanics approaches such as harmonic analysis and TST. It is expected that this accurate yet efficient dynamic strategy can be a powerful tool in understanding reaction mechanisms and reactivity of a catalytic surface system, and further guides the rational design of heterogeneous catalysts.","PeriodicalId":72565,"journal":{"name":"ChemRxiv : the preprint server for chemistry","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2021-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"45703177","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Facile synthesis of novel heterogenous Rh/COF catalyst and its application in tandem selective transfer hydrogenation and mono-methylation of Nitro compounds with Methanol","authors":"Jianguo Liu, Mingyue Zhang, Nan Wang, Xiuzhi Wei, Bo Yang, Longlong Ma","doi":"10.33774/chemrxiv-2021-6qtnd","DOIUrl":"https://doi.org/10.33774/chemrxiv-2021-6qtnd","url":null,"abstract":"The development of transition metal heterogeneous catalysts for economical and effective synthesis of N-methylamine, especially for the mono-methylation of amines is still challenging. Herein, two unprecedented Rh-supported COFs heterogeneous catalysts Rh/MelCOF was facile synthesized by Schiff base reaction using melamine as a precursor, and for the first time, it was successfully applied to the effective and high selective tandem reaction of transfer hydrogenation and mono-methylation of nitroaromatic hydrocarbons with methanol as C1 and hydrogenation source, with water as the only by-product. A series of nitroaromatic hydrocarbons, including heterocyclic or sterically hindered derivatives, can be well tolerated and the catalyst could also be reused 4 times without losing significant reactivity. At the same time, the study of the Rh/MelCOF mechanism supports the hydrogen borrowing mechanism and puts forward the reaction pathway of azobenzene as an intermediate, which is better than the hydrogen transfer pathway from N-phenylhydroxylamine to aniline directly. This work not only expands the COF family but also provides an effective way to obtain mono N-methylated amines from nitroaromatic hydrocarbons, as well as the detailed mechanism of Rh/COF catalyzed tandem transfer hydrogenation and mono-methylation of amines.","PeriodicalId":72565,"journal":{"name":"ChemRxiv : the preprint server for chemistry","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2021-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"49240513","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"An Efficient Synthesis of Tetrodotoxin","authors":"David B. Konrad, Peter Ruehmann, Hiroyasu Ando, Belinda E. Hetzler, Bryan S. Matsuura, D. Trauner","doi":"10.33774/chemrxiv-2021-xkftp","DOIUrl":"https://doi.org/10.33774/chemrxiv-2021-xkftp","url":null,"abstract":"Tetrodotoxin (TTX) is an indispensable probe in neuroscience, a biosynthetic and ecological enigma, and one of the most celebrated targets of synthetic chemistry. Here, we present a stereoselective synthesis of TTX that proceeds in 22 steps starting from a readily available glucose derivative. The central cyclohexane ring of TTX and its α-tertiary amine moiety was established via the intramolecular 1,3-dipolar cycloaddition of a nitrile oxide, followed by alkynyl addition to the resultant isoxazoline. After some carefully chosen protecting group manipulations, a ruthenium-catalyzed hydroxylactonization set the stage for the formation of its dioxa-adamantane core. Installation of the guanidine, oxidation of a primary alcohol, and late-stage epimerization of the resultant aldehyde gave a mixture of TTX and anhydro TTX. Our synthesis represents one of the most effective of TTX reported to date and could give ready access to biologically active derivatives.","PeriodicalId":72565,"journal":{"name":"ChemRxiv : the preprint server for chemistry","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2021-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"44901113","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mechanistic insights of key host proteins and potential repurposed inhibitors regulating SARS-CoV-2 pathway","authors":"Debabrata Pramanik, Aiswarya Pawar, Sudip Roy, Jayant K Singh","doi":"10.33774/chemrxiv-2021-65skk","DOIUrl":"https://doi.org/10.33774/chemrxiv-2021-65skk","url":null,"abstract":"The emergence of pandemic situations originated from SARS-CoV-2 and its new variants created worldwide medical emergencies. Due to the non-availability of efficient drugs and vaccines, hundreds of thousands of people succumbed to death intoxicated by this virus. At these emergency hours, repurposing existing drugs can effectively treat patients critically infected by SARS-CoV-2. Using a high-throughput screening approach, we validated a list of potential repurposed drugs, like Nafamostat, Camostat, Silmitasertib, Valproic acid, Zotatifin, and essential host target proteins HDAC2, eIF4E2, CSK22, that are essential for viral mechanism. We determined multiple dissociation pathways of repurposed drugs, suggesting the availability of sub pockets within the host target proteins. We showed the preferential residues involved in the (un)binding kinetics of the ligands correlated to the underlying mechanism of the host protein activity. Interestingly, the residues we obtained for HDAC2 and CSK22 target proteins, which we highlighted, are also involved in the catalytic activity. The mechanistic insight presented in this work is envisaged to help use these key host proteins and potential repurposed drugs as a treatment for the SARS-CoV-2 virus.","PeriodicalId":72565,"journal":{"name":"ChemRxiv : the preprint server for chemistry","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2021-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"42799479","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"An Efficient GaMD Multi-Level Enhanced Sampling Strategy for Polarizable Force Fields Simulations of Large Biological Systems","authors":"Frédéric Célerse, Theo Jaffrelot-Inizan, Louis Lagardère, Olivier Adjoua, Pierre Monmarché, Yinglong Mia, E. Derat, Jean‐Philip Piquemal","doi":"10.33774/chemrxiv-2021-ggjfx","DOIUrl":"https://doi.org/10.33774/chemrxiv-2021-ggjfx","url":null,"abstract":"We introduce a novel multi-level enhanced sampling strategy grounded on Gaussian accelerated Molecular Dynamics (GaMD). First, we propose a GaMD multi-GPUs -accelerated implementation within Tinker-HP. For the specific use with the flexible AMOEBA polarizable force field (PFF), we introduce the new \"dual–water\" GaMD mode. By adding harmonic boosts to the water stretching and bonding terms, it accelerates the solvent-solute interactions while enabling speedups with fast multiple–timestep integrators. To further reduce time-to-solution, we couple GaMD to Umbrella Sampling (US). The GaMD—US/dual–water approach is tested on the 1D Potential of Mean Force (PMF) of the CD2–CD58 system (168000 atoms) allowing the AMOEBA PMF to converge within 1 kcal/mol of the experimental value. Finally, Adaptive Sampling (AS) is added enabling AS–GaMD capabilities but also the introduction of the new Adaptive Sampling–US–GaMD (ASUS–GaMD) scheme. The highly parallel ASUS–GaMD setup decreases time to convergence by respectively 10 and 20 compared to GaMD–US and US.","PeriodicalId":72565,"journal":{"name":"ChemRxiv : the preprint server for chemistry","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2021-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"42628909","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Poly(thioether phenyl acrylate) Based Micelles Show Exclusively ROS-triggered Breakdown","authors":"I. Piergentili, P. Bouwmans, Luuk Reinalda, Reece W. Lewis, Benjamin Klemm, Huanhuan Liu, R. D. de Kruijff, A. Denkova, R. Eelkema","doi":"10.33774/chemrxiv-2021-5wn7m","DOIUrl":"https://doi.org/10.33774/chemrxiv-2021-5wn7m","url":null,"abstract":"In certain tumor and diseased tissues, reactive oxygen species (ROS), such as H2O2, are produced in higher concentrations than in healthy cells. To date, only few examples of drug delivery and release systems responds selectively to these small but significantly elevated ROS concentrations. In addition, assuring the stability of the polymer-based carrier in “healthy” biological conditions is still a challenge in the field of oxidation-sensitive materials. Here, we present ROS-responsive block copolymer micelles capable of achieving micellar disruption over days in the presence of 2 mM H2O2 and within hours under higher concentrations of H2O2 (60 – 600 mM). At the same time, these micelles are stable for over two weeks in oxidant-free physiological (pH = 7.4, 37°C) and for at least six days in mildly acidic (pH = 5.0 and pH = 6.0, 37°C) conditions. The observed selectivity is programmed into the material using a 4-(methylthio)phenyl ester based logic gate. Here, oxidation of the thioether moiety results in a large increase in ester hydrolytic lability, effectively switching the ester hydrolysis from off to on. The concept represents a step forward to realize signal responsive drug delivery materials capable of selective action in biological environments.","PeriodicalId":72565,"journal":{"name":"ChemRxiv : the preprint server for chemistry","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2021-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"46577381","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Catalytic Deracemization of α-Branched Aldehydes via Visible Light Promoted E/Z Isomerization of Enamine Intermediate","authors":"Mouxin Huang, Long Zhang, Tianrun Pan, S. Luo","doi":"10.33774/chemrxiv-2021-wrrws","DOIUrl":"https://doi.org/10.33774/chemrxiv-2021-wrrws","url":null,"abstract":"Catalytic deracemization of α-branched aldehydes represents an unmet challenge with fundamental importance in carbonyl chemistry. In this work, we report a photochemical E/Z isomerization strategy for the deracemization of α-branched aldehydes by using simple aminocatalysts and readily available photosensitizers. Various racemic α-branched aldehydes could be directly transformed into their corresponding single enantiomers in high enantioselectivity. Rapid photodynamic E/Z isomerization and highly stereospecific iminium/enamine tautomerization are two key factors that underlie the highly effective enantio-enrichment. This study presents a distinctive photochemical E/Z isomerizing strategy for externally tuning enamine catalysis.","PeriodicalId":72565,"journal":{"name":"ChemRxiv : the preprint server for chemistry","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2021-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"48721276","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The catalytic mechanism of the Suzuki-Miyaura reaction","authors":"Juliet Macharia, C. Joshi, Joseph A. Izzo, Victor Wambua, Sungjin Kim, Jennifer S. Hirschi, Mathew J. Vetticatt","doi":"10.33774/chemrxiv-2021-64461","DOIUrl":"https://doi.org/10.33774/chemrxiv-2021-64461","url":null,"abstract":"Abstract: Experimental and theoretical 13C kinetic isotope effects are utilized to obtain atomistic insight into the catalytic mechanism of the Pd(PPh3)4 catalyzed Suzuki-Miyaura reaction of aryl halides and aryl boronic acids. Under catalytic conditions, we establish that oxidative addition of aryl bromides occurs to a 12-electron monoligated palladium complex (Pd(PPh3)). For aryl iodides, the first irreversible step in the catalytic cycle precedes oxidative addition and is shown to be binding of the iodoarene to Pd(PPh3). Our results suggest that the commonly proposed oxidative addition to the 14-electron Pd(PPh3)2 complex can occur only in the presence of excess added ligand or under stoichiometric conditions. The transmetalation step, under catalytic conditions, is shown to proceed via a tetracoordinate boronate (8B4) intermediate with a Pd-O-B linkage.","PeriodicalId":72565,"journal":{"name":"ChemRxiv : the preprint server for chemistry","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2021-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"47093383","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Understanding the Role of Geometric and Electronic Structure in Bioinspired Catalyst Design: the Case of Formate Dehydrogenase","authors":"Mingjie Liu, Azadeh Nazemi, Michael Taylor, Aditya Nandy, Chenru Duan, A. Steeves, H. Kulik","doi":"10.33774/chemrxiv-2021-397ph","DOIUrl":"https://doi.org/10.33774/chemrxiv-2021-397ph","url":null,"abstract":"The design of bioinspired synthetic inorganic molecular complexes is challenging, due to a lack of understanding of enzyme action and the degree to which that action can be translated into mimics. Exemplary of this challenge is the reversible conversion of formate into CO2 by formate dehydrogenase (FDH) enzymes with Mo/W centers in large molybdopterin cofactors. Despite numerous efforts to synthesize Mo/W-containing molecular complexes, none have been demonstrated to reproduce the full reactivity of FDH. Here, we carry out a large-scale, high-throughput screening study on all mononuclear Mo/W complexes currently deposited in Cambridge Structural Database (CSD). Using density functional theory, we systematically investigate the individual effects of metal identity, ligand identity, oxidation state, and coordination number on structural, electronic and catalytic properties. We compare our results on molecular complexes with quantum mechanics/molecular mechanics simulations on a representative FDH enzyme to further elucidate the influence of the enzyme environment. These comparisons reveal that the enzyme environment primarily influences the metal-local geometry, and these metal-local structural variations can improve catalysis. Through a series of computational mutations on molecular complexes, we extend beyond the CSD structures to further identify the limits of varied chalcogen and metal identity. This broad set and comparison reveal relatively little variation of electronic properties of the metal center due to the presence of the enzyme environment or changes in metal-distant ligand chemistry. Instead, these properties are found to be much more sensitive to the identity of the metal and the nature of the bound terminal chalcogen.","PeriodicalId":72565,"journal":{"name":"ChemRxiv : the preprint server for chemistry","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2021-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41771439","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}