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Hydrogenation of Organic Molecules via Direct Mechanocatalysis
No full textMechanochemical hydrogenation of unsaturated C-C and C-O, as well as N-O and C-X bonds is successfully achieved without the use of solvents, ligands, or catalyst powders via ball milling. A variety of catalysts are electroplated onto the walls of the milling vessel, allowing for simple recycling and reuse of the catalytic material. Hydrogen gas is directly introduced into the milling vessel, eliminating the need for hydrogen donor compounds which contribute to waste production and suboptimal atom economy. This approach enables quantitative hydrogenation of unsaturated carbon-carbon bonds at ambient temperature and pressures as low as 1.5 bar in as little as 20 minutes. Mechanistic investigations suggest the reaction to be following established mechanisms for hydrogenation. Finally, chemoselective hydrogenation of various reducible functional groups was explored, demonstrating the versatility and efficiency of this solvent-free mechanochemical approach with simple catalyst recycling for hydrogenation reactions
Characterizing the Stability of Ultra-Thin Metal Oxide Catalyst Films in Non-thermal Plasma CO2 Reduction Reactions
No full textThe use of metal oxide catalysts to enhance plasma CO2 reduction has seen significant recent development towards processes to reduce greenhouse gas emissions and produce renewable chemical feedstocks. While plasma reactors are effective at producing the intended chemical transformations, the conditions can result in catalyst degradation. Atomic layer deposition (ALD) can be used to synthesize complex, hierarchically structured metal oxide plasma catalysts that, while active for plasma CO2 reduction, are particularly vulnerable to degradation due to their high surface area and nanoscopic thickness. In this work, we characterized the effects of extended non-thermal, glow-discharge plasma exposure on ALD synthesized, ultra-thin film (< 30 nm) TiO2 and ZnO catalysts. We used x-ray diffraction, reflectivity, and spectroscopy to compare films exposed to a CO2 plasma to ones exposed to an Ar plasma and to ones annealed in air. We found that the CO2 plasma exposure generated some surface reduction in TiO2 and increased surface roughening by a small amount, but did not initiate any phase changes or crystallite growth. The results suggest that ALD-deposited metal oxide films are robust to low pressure CO2 plasma exposure and are suitable as catalysts or catalyst supports in extended reactions
Molecular Probe to Visualize Effect of Glycolytic Inhibitor on Reducing NADH levels in the Cellular System
No full text1,4-Dihydronicotinamide adenine dinucleotide hydride (NADH) is an essential coenzyme existing in all living organisms. Due to its involvement in different biological process, fluorescence imaging of intracellular NADH levels at different pathological conditions has emerged as an interesting area of research. We report here the exploration of a fluorescent probe MQ-CN-BTZ as dual channel NADH imaging agent (green and red channel) for cellular system. Interestingly, depending on the ratio between probe and NADH concentration in solution phase, the probe showed emission at ~530 nm and ~660 nm when excited at 475 nm. It is to be noted that the probe showed very large Stokes shift of ~180 nm with respect to the longer wavelength emission with good fluorescence response towards NADH. In general, such large Stokes shift is highly beneficial for imaging applications largely due to better separation between emission and excitation spectra, and reduced spectral overlap. Finally, the probe was utilized to image the event of glycolysis pathway by employing 3-bromopyruvic acid (3-BrPA) as a glycolytic inhibitor that inhibits the activity of glyceraldehyde phosphate dehydrogenase (GAPDH) enzyme involved in a crucial step of the glycolysis. As the depletion of the NADH levels corresponds to the inactivity of GADPH upon treatment with inhibitor, we imaged the modulation of NADH concentration in cellular system in the presence of 3-BrPA inhibitor indicating the importance of glycolysis step in elevating NADH levels. Overall, the present study attempts to demonstrate the importance of fluorescent probe for imaging intracellular NADH in the presence of glycolytic inhibitor
Improved description of environment and vibronic effects with electrostatically embedded ML potentials
No full textIncorporation of environment and vibronic effects in simulations of optical spectra and excited state dynamics is commonly done combining molecular dynamics with excite state calculations, which allows to estimate the spectral density describing the frequency-dependent system-bath coupling strength. The need for efficient sampling, however, usually leads to the adoption of classical force fields, despite well-known inaccuracies due to the mismatch with the excited state method. Here we present a multiscale strategy that overcomes this limitation by combining EMLE simulations based on electrostatically embedded ML potentials with the QM/MMPol polarizable embedding model to compute the excited states and spectral density of 3-methyl-indole, the chromophoric moiety of tryptophan that mediates a variety of important biological functions. Our protocol provides highly accurate results that faithfully reproduce their ab initio QM/MM counterparts, thus paving the way for accurate investigations on the interrelation between the timescales of biological motion and the photophysics of tryptophan and other biosystems
Thermochemical Heterolytic Hydrogenation Catalysis Proceeds Through Polarization-Driven Hydride Transfer
No full textHeterolytic hydrogenations, which split H2 across a hydride acceptor and proton acceptor, are a key class of reactions that span the chemical value chain, including CO2 hydrogenation to formate and NADH regeneration from NAD+. The dominant mechanistic models for heterogeneous catalysis of these reactions invoke classical surface mechanisms that ignore the role of interfacial charge separation. Herein, we quantify the electrochemical potential of the catalyst during turnover and uncover evidence supporting an interfacial electrochemical hydride transfer mechanism for this overall thermochemical reaction class. We find that the proton acceptor induces spontaneous electrochemical polarization of the metal catalyst surface, thereby controlling the thermodynamic hydricity of the surface M–H intermediates and driving rate-determining electrochemical hydride transfer to the hydride acceptor substrate. Overall, this model invokes that heterolytic hydrogenations proceed via the coupling of two electrochemical half-reactions, the hydrogen reduction reaction (HRR) and hydrogen oxidation reaction (HOR), which convert H2 to hydride and proton, respectively. This mechanistic framework, which applies across diverse reaction media and for the hydrogenation of CO2 to formate and NAD+ to NADH, enables the determination of intrinsic reaction kinetics and exposes design principles for the future development of sustainable hydrogenation reactivity
Two-Stage Growth of Solid Electrolyte Interphase on Copper: Imaging and Quantification by Operando Atomic Force Microscopy
No full textThe solid electrolyte interphase (SEI) plays a key role in the aging of lithium-ion batteries. The engineering of advanced negative electrode materials to increase battery lifetime relies on accurate models of SEI growth, but quantitative measurement of SEI growth rates remains challenging due to their nanoscale heterogeneity and environmental sensitivity. In this work, using operando electrochemical atomic force microscopy, we track the growth of SEI on copper in a carbonate electrolyte. From operando measurements of SEI thickness and irreversible electrochemical capacity, we directly visualize the dual growth regimes of the SEI, observing an early-stage primary SEI approximately 10 times more “electrochemically compact” than later-stage secondary SEI, as quantified via the incremental thickness per charge passed. While primary SEI is responsible for about half of the irreversible capacity loss (in a 24 h period), it accounts for only a tenth of thickness. We also show that nanoscale defects on the copper substrate play a key role in determining the non-uniform growth morphology of the SEI, thus providing novel, direct evidence that initial SEI growth is not purely transport-limited. Our experiments reveal SEI grows by two modes: first a reaction-limited nucleation and growth of a dense, passivating primary SEI layer, governed by ion-coupled electron transfer kinetics; and subsequently by diffusion-limited growth of a porous secondary SEI layer, once the primary SEI fully passivates the electrode surface
Visible Light Mediated Photoclick Reactions of Diazoenals: Direct Access to Bicyclo[4.1.0]heptane-Fused Polycycles with Potential Application as Insulin Aggregation Inhibitors
No full textVisible light-induced photoclick chemistry is a powerful synthetic tool, combining the precision of photochemistry with the modularity of click reactions. Herein, we report a novel class of bench-stable acceptor-acceptor diazo compounds diazoenals, that enable visible light-mediated photoclick reactions with vinyl arenes, generating cyclopropane-fused tetralin, decalin, tetrahydrophenanthrene and tetrahydrocarbazole motifs having up to five stereocenters with excellent yield and diastereoselectivity, under aqueous conditions. These diazoenals exhibit enhanced photophysical properties, absorbing in the visible region and, upon irradiation, generate free enalcarbene intermediates that facilitate a selective mode of reactivity. Notably, these new class of photoclick products were found to be effective inhibitors of insulin aggregation, and the enal- cyclopropane-fused tetrahydrocarbazole completely rescued HEK293T cells from insulin fibril me-diated-toxicity, highlighting the bioactive and biocompatible nature of this molecule. This work underscores the versatility of diazoenals in visible light-driven transformations, particularly in photoclick reactions, offering a sustainable and biocompatible synthetic platform for complex molecular architectures with potential bio-applications
Rational exploration of 2,4-diaminopyrimidines as DHFR inhibitors active against Mycobacterium abscessus and Mycobacterium avium, two emerging human pathogens
No full textNontuberculous mycobacteria (NTM) are emerging human pathogens linked to severe pulmonary diseases. Current treatments involve the prolonged use of multiple drugs and are often ineffective. Bacterial dihydrofolate reductase (DHFR) is a key enzyme targeted by antibiotics in Gram-negative bacterial infections. However, existing DHFR inhibitors designed for Gram-negative bacteria often fail against mycobacterial DHFRs. Here, we detail the rational design of NTM DHFR inhibitors based on P218, a malarial DHFR inhibitor. We identified 8, a 2,4-diaminopyrimidine exhibiting improved pharmacological properties and activity against purified DHFR and whole cell cultures of two predominant NTM species: Mycobacterium avium and Mycobacterium abscessus. This study underscores the potential of 8 as a promising candidate for the in vivo validation of DHFR as an effective treatment against NTM infections
Solvent Effect on the Hydroxyl Radical Scavenging Activity of New Isothiocyanate Compounds
No full textThe role of natural-based isothiocyanates Cp1-Cp4, i.e., allylisothiocyanate, 1-isothiocyanate-3-methylbutane, 4-methylphenyl isothiocyanate, and 2-phenylethyl isothiocyanate in scavenging highly reactive HOꞏ-radical was studied using Density Functional Theory at M06-2X/6-311++G(3df,3pd)//M06-2X/6-311++G(d,p) level of theory. Formal hydrogen transfer, radical adduct formation, and single electron transfer mechanisms were considered in water and pentyl ethanoate (PEA, to mimic the lipid environment). The results illustrated the high HOꞏ-scavenging activity of the isothiocyanate compounds with rate constants of about 108 - 109 M-1s-1. Allylisothiocyanate Cp1 represents the most efficient HOꞏ-scavenger with koverall of 5.20 × 109 M-1s-1 in water, and 1.85 × 109 M-1s-1 in PEA. Moreover, the rate constants of HOꞏ-reactions with the studied isothiocyanates in the aqueous medium are comparable with that of several biological molecules. These results allow us to enrich the data source on effective antioxidants to reduce excess free radicals and limit damaging effects on biological molecules
DOPtools: a Python platform for descriptor calculation and model optimization. Overview and usage guide
No full textDOPtools (Descriptors and Optimization tools) platform is a Python library for calculation of chemical descriptors and hyperparameters optimization, building and validation of QSPR models. While a variety of existing tools and libraries can calculate various molecular de- scriptors, their output format is often unique, which complicates their connection to standard machine learning libraries. DOPtools provides a unified API for the calculated descriptors as an input for the scikit-learn library. Moreover, DOPtools has a command line interface for automatic calculation of various descriptors on server side and for eventual hyperparameters optimization of statistical models. The modular nature of the code allows easy additions of algorithms if required by the end user. The code for the platform is freely available at GitHub: https://github.com/POSidorov/DOPtools