Local Reactivity Research Articles

Receptor-Based Pharmacophore Modelling of a series of ligands used as inhibitors of the SARS-CoV-2 virus by complementary theoretical approaches, molecular docking, and reactivity descriptors.

Background: A coronavirus identified in 2019, SARS- CoV- 2, has caused a pandemic of respiratory illness, called COVID- 19. Most people with COVID-19 experience mild to moderate symptoms and recover without the need for special treatments. The SARS‑CoV‑2 RNA‑dependent RNA polymerase (RdRp) plays a crucial role in the viral life cycle. The active site of the RdRp is a very accessible region, so targeting this region to study the inhibition of viral replication may be an effective therapeutic approach. For this reason, this study has selected and analysed a series of ligands used as SARS-CoV-2 virus inhibitors, namely: the Zidovudine, Tromantadine, Pyramidine, Oseltamivir, Hydroxychoroquine, Cobicistat, Doravirine (Pifeltro), Dolutegravir, Boceprevir, Indinavir, Truvada, Trizivir, Trifluridine, Sofosbuvir and Zalcitabine. Methods: These ligands were analyzed using molecular docking, Receptor-Based Pharmacophore Modelling. On the other hand, these outcomes were supported with chemical reactivity indices defined within a conceptual density functional theory framework. Results: The results show the conformations with the highest root-mean-square deviation (RMSD), have π-π stacking interaction with residue LEU141, GLN189, GLU166 and GLY143, HIE41, among others. Also was development an electrostatic potential comparison using the global and local reactivity indices. Conclusions: These studies allow the identification of the main stabilizing interactions using the crystal structure of SARS‑CoV‑2 RNA‑dependent RNA polymerase. In this order of ideas, this study provides new insights into these ligands that can be used in the design of new COVID-19 treatments. The studies allowed us to find an explanation supported in the Density Functional Theory about the chemical reactivity and the stabilization in the active site of the ligands.

Chemical reactivity of 3-substituted-6,8-dimethylchromones towards 1H-benzimidazol-2-ylacetonitrile and 5-amino-2,4-dihydro-3H-pyrazol-3-one: Spectroscopic, theoretical and in silico ADME studies

The reactivity of 1H-benzimidazol-2-ylacetonitrile and 5-amino-2,4-dihydro-3H-pyrazol-3-one, as nucleophilic reagents, was examined towards some 3-substituted-6,8-dimethylchromones 2a-d. A diversity of novel pyrido[1,2-a]benzimidazoles, chromeno[2,3-b]pyridines, pyrazolo[3,4-b]pyridines and chromenopyrazolopyridines was efficiently synthesized through different chemical transformations; depending on the functional group present at C-3 position of the chromone moiety. With B3LYP/6–311 G(d,p) basis set in the ground state, density functional theory (DFT) is used to determine the molecular geometry of synthesized compounds. The reactivity of the current compounds was studied by global reactivity descriptors at the same level of theory. In order to forecast the reactive locations on the starting substrates 2a-d for nucleophilic and electrophilic attacks, Fukui functions (local reactivity descriptors) were computed at the same level of theory. On the other hand, molecular electrostatic potential (MEP) surface maps were used to identify the nucleophilic and electrophilic sites. Moreover, 1H and 13C NMR chemical shift values in the ground state was calculated using the Gauge-Including Atomic Orbital (GIAO) technique, and the predicted values were compared with the experimental results. To interpret the nonlinear optical (NLO) property of the synthesized compounds, the dipole moment, polarizability, and first hyperpolarizability values have been measured (in the range β = 0.38 × 1030 - 3.28 × 10−30 esu). First hyperpolarizabilities of the investigated compounds indicate promising candidates for nonlinear optical applications. Also, using web-based platforms, in silico ADME calculations were performed.

The use of global and local reactivity descriptors of conceptual DFT to describe toxicity of benzoic acid derivatives

The present study explores the use of global and local quantum reactivity descriptors and conceptual density functional theory (cDFT), as well as descriptors of atomic-quantum topology (QTAIM), to describe the structure–toxicity relationship (STR) for 37 compounds derived from benzoic acid, employing the median lethal dose logarithm (log LD50) as a parameter. The method was validated using a coefficient of determination (R2) of 0.8285 and a leave-one-out cross-validation (Q2LOO) of 0.7138, thus fulfilling the statistical criteria indicated for models generated in QSARINS software. The descriptors closely related to the toxicity of the compounds were EHOMO(N−1), ∇2ρ(r)(BCP2), ∇2ρ(r)(BCP5), QH4Hirshfeld, QYY(C1), and ∑q-meta. This finding both enabled the reactivity of the benzoic acid derivatives to be interpreted and facilitated an understanding of the potential chemical bonds with enzymes, such as serine, in a biological environment.

Monte Carlo and DFT calculations on the corrosion inhibition efficiency of some benzimide molecules

Calculations using density functional theory (DFT) and Monte Carlo methods were performed on 2-methylbenzimidazole, 2-mercaptobenzimidazole, 2-aminobenzimidazole, benzotriazole, and benzimidazole to determine their corrosion inhibition efficiency. The molecular structure was optimized geometrically using DFT calculations at the B3LYP/6– 311 G++(d,p) and b2plypd3/aug-cc-pvdz basis set level in protonated and non-protonated species in gas and water. In this study, HOMO, LUMO, bandgap, ionization energy, electronegativity, hardness, softness, electrophilicity and nucleophilicity, electron transfer, back donation energy and condensed Fukui indices are used to assess a molecule's local reactivity. Theoretical investigations can precisely establish the geometrical dimensions of a molecule and correctly explain the quantum properties of inhibitors. The mechanism of interaction between inhibitors and metal surfaces in a specified molecule is studied using molecular dynamics. The benzimidazole functional groups absorbed energy linearly on metal surfaces, with quantum characteristics determined using density functional theory and an ab initio technique. Importantly, the findings of this conceptual model are consistent with the corrosion inhibition efficiency of earlier experimental investigations.

Effective Screening Descriptor for MXenes to Enhance Sulfur Reduction in Lithium-Sulfur Batteries.

MXenes, two-dimensional transition (2D) metal carbides/nitrides, have shown promise as cathodic catalysts for accelerating the conversion of lithium polysulfides (LiPSs) in lithium-sulfur (Li-S) batteries due to their diverse redox-active sites and rapid electron transfer. However, efficiently screening the optimal cathodic catalysts out of thousands of MXenes is challenging. To address this, we developed a model that accurately predicts the thermodynamic energy barrier of the rate-limiting step in Li-S batteries. Our model relates the local chemical reactivity of the MXene sites to the p-band center of the terminations and the electronegativity of subsurface transition metals. The accuracy of the model was verified through density functional theory calculations and contrast experiments in pure and Zn-doping MXenes qualitatively. By utilizing this model, we screened a large library of MXenes (27 types of five-atom-layer MXenes) and identified Ti2CS2, Mo2CS2, and W2CS2 as potential cathodic catalysts for Li-S batteries.

Exploring the influence of structural characteristics on the stability of bioregulators in natural environmental conditions

This research aimed to identify the plant bioregulator with lower environmental risk for improving fruit and grape production through the comprehensive field, laboratory, and computational experiments. Plant bioregulators are compounds playing a vital role in the development of plants, regulating diverse cellular processes. Among these compounds, Ormoroc and Globaryll are widely known formulations extensively applied for improving the quality of crops. However, overusing bioregulators in food production has led to their presence in different water resources, threatening to designate them as severe pollutants of natural resources. Field experiments were conducted to identify which bioregulator improves the quality of selected fruit and grape varieties. The laboratory study involved photolysis and hydrolysis experiments in pure and rain waters, aimed at studying the stability of the mentioned bioregulators under naturally occurring conditions. The laboratory experiments also included the exploration of chemical and biochemical oxygen demand. The computational analysis involved density functional theory calculations and molecular dynamics simulations in investigating how the structural characteristics of the compounds affect their local reactivity properties. The study indicates that the application of Ormoroc improves fruit and grape quality to a greater extent. However, the active component of Ormoroc is less stable under the influence of solar irradiation and water, reducing the likelihood of water pollution.

Exploring the Synergistic Effect of Tegafur-Syringic Acid Adduct Against Breast Cancer through DFT Computation, Spectroscopy, Pharmacokinetics and Molecular Docking Simulation

The most prevalent kind of cancer and the main reason for cancer-related deaths in women is breast cancer. Synergistic drug delivery plays an effective role in the treatment of cancer by targeting various proteins underlying different mechanism. In this present study, a thorough analysis of the tegafur syringic acid adduct compound using density functional theory, molecular docking and pharmacokinetic prediction has been done. The PED value was given to the estimated vibrational wavenumbers. The molecule’s UV-Vis absorption spectra in the gas phase and liquid phase (water), were exhibited as π→π* electronic transitions. In order to determine the stability and molecular reactivity of the molecule, the HOMO-LUMO energies, energy gap, molecular electrostatic potential surface and mulliken atomic charge distribution were determined. Natural bond orbital analysis was used to determine the molecule’s second order perturbation energy E(2) values and potential reactive location was revealed through local reactivity descriptors. The Hirshfeld surface analysis showed that H…H (40.9%), O…H/H…O (27.2%), C…C (8%), O…C/C…O (7.8%), F…H/H…F (5.9%), C…H/H…C (5.5%), and N…C/C…N (2.9%) have the highest percentage contributions of the most important interactions. Thermodynamic characteristics like enthalpy, specific heat capacity and entropy were calculated. The physiochemical, absorption, distribution, metabolism, excretion and toxicity (ADMET) properties were predicted and represented the safety profile of adduct compound and the docking studies exhibited the binding potential of the adduct against the breast cancer proteins and highest binding affinity was observed against GSK3β with docking score of −9.7 Kcal/mol.

Synthesis, Spectroscopic Analysis, Charge and Proton Transfer Interaction Studies, In-Vitro, and In-Silico Antimicrobial, Pharmacokinetics Studies of Piperazin-1-Ium 4-Aminobenzoate Monohydrate: A Density Functional Theory Approach

Piperazin-1-ium 4-aminobenzoate monohydrate (PPAB) single crystals were grown by slow evaporation method. The grown crystal PPAB has been characterized by single-crystal X-ray diffraction, FTIR, FT-Raman, and UV-visible analysis. The B3LYP method and 6-311G (d, p) basis set were used to optimize the structure. The title compound was investigated theoretically and experimentally by FT-IR, FT-Raman, and UV-Vis spectral analysis. The presence of various functional groups in the structure was elucidated by FTIR and FT-Raman spectral studies. The intermolecular interactions within the crystal structure were investigated using Hirshfeld surface analysis. The crystal packing diagram reveals interesting non-covalent interactions involving C–H···O, N–H···O, and N–H···N hydrogen bonds, leading to the generation of 3D supramolecular architecture. The charge transfer within the molecule was deeply analyzed by using the NBO approach. The molecular electrostatic potential (MEP) and the local reactivity descriptors, such as Fukui function (fk +, fk −) analyses were performed to determine the reactive sites within the molecule. The HOMO and LUMO analysis was used to determine the chemical reactivity and bioactivity of the molecule. Hole-electron analysis was performed to analyze the charge transfer in an excited state. Based on the hole-electron analysis, the inter-fragment charge transfer (IFCT) analysis establishes the amount of charge transfer among different fragments. Topological analyses, such as AIM, RDG, and ELF were carried out to identify the non-covalent interaction within the molecule. The molecular docking studies of the molecule are performed to investigate the binding affinity of the ligand with the protein receptor. Drug-likeness properties, such as Lipinski’s rule of five, adsorption, distribution, metabolism, excretion, and toxicity (ADMET) have been investigated by in silico web-based tools like SwissADME and ADMETlab.

Synthesis, theoretical and experimental spectroscopic techniques, proton transfer study on Metachlorphenprop-p-anisidine: In-vitro and in-silico antimicrobial analysis

The structural and packing feature of novel Metachlorphenprop-p-anisidine (MCPA) single crystal was grown by refluxing stoichiometric amount of Metachlorphenprop (MCP) and p-anisidine (PAS) in ethanol, was investigated by single crystal X-ray diffraction. The title compound was investigated theoretically and experimentally by FT-IR, FT-Raman, TG-DTA and UV–Vis spectra. The theoretical optimized geometrical parameters and vibrational analysis were performed by density functional theory (DFT) with the B3LYP method at 6–311 G (d,p) basis set. The optimized geometrical parameters obtained by DFT calculations were in good agreement with the experimental data. Various intermolecular interactions involved in MCPA were analysed using different topological analysis atoms-in-molecule (AIM), reduced density gradient (RDG), electron localization function (ELF) and natural bond orbital (NBO) analysis. The stability of the molecule arising from intermolecular interaction and charge delocalization have been analysed using NBO analysis. Molecular electrostatic potentials (MEP) was performed to analyse the reactive area of the title molecule, local chemical reactivity was studied by population analysis and Fukui function analysis. The thermal behaviour of the MCPA crystal was analysed by TG-DTA analysis. Hole-electron interaction study divulge that S1-S4 undergo charge transfer excitation. The mechanical strength of the grown material proves that it is a soft material. Molecular docking was performed to confirm the stability of the protein-ligand complex. The results shows that the title compound has antibacterial properties as well as antifungal activities against Escherichia coli and Aspergillus niger organisms. The pharmacokinetics and drug likeness were also performed on titled molecule for the confirmation of drug-like character of title molecule.

Experimental (FT‐Raman, FT‐IR and NMR) and theoretical (DFT) calculations, thermodynamic parameters, molecular docking and NLO (non-linear optical) properties of N‐(2,6‐dimethylphenyl)‐1‐piperazineacetamide

Abstract Theoretical and experimental studies are performed on the new organic–inorganic hybrid molecule N‐(2,6‐dimethylphenyl)‐1‐piperazineacetamide. The vibrational spectra of the molecule are characterized using FT‐IR and FT‐Raman in the range 4000–600 cm−1 and 4000–100 cm−1, respectively. Density functional theory with B3LYP/3‐21G and B3LYP/cc‐pVDZ basis sets is used to calculate energy, geometrical structure, and vibrational modes of stretching, bending, and torsion. The VEDA software Autodock Vina revealed a good binding is employed to calculate the detailed vibrational assignments. The theoretical and experimental vibrational data are compared to support the present study. Density functional theory is used to calculate thermodynamic parameters (heat capacity, entropy, and enthalpy) and nonlinear optical properties. The software Gaussian09W and Gaussview 6.0 are used for theoretical calculations. Molecular docking studies are carried out to investigate the effect of the titled molecule against various proteins such as SARS‐CoV‐2 that affect the immune system in humans. Chemical shifts are identified using carbon and proton NMR. Non‐covalent interactions are studied using a reduced density gradient. The chemical reactivity and selectivity for a local reactivity site are analyzed with the help of Fukui functions.

Transcriptome-wide probing reveals RNA thermometers that regulate translation of glycerol permease genes in Bacillus subtilis.

RNA structure regulates bacterial gene expression by several distinct mechanisms via environmental and cellular stimuli, one of which is temperature. While some genome-wide studies have focused on heat shock treatments and the subsequent transcriptomic changes, soil bacteria are less likely to experience such rapid and extreme temperature changes. Though RNA thermometers (RNATs) have been found in 5' untranslated leader regions (5' UTRs) of heat shock and virulence-associated genes, this RNA-controlled mechanism could regulate other genes as well. Using Structure-seq2 and the chemical probe dimethyl sulfate (DMS) at four growth temperatures ranging from 23°C to 42°C, we captured a dynamic response of the Bacillus subtilis transcriptome to temperature. Our transcriptome-wide results show RNA structural changes across all four temperatures and reveal nonmonotonic reactivity trends with increasing temperature. Then, focusing on subregions likely to contain regulatory RNAs, we examined 5' UTRs to identify large, local reactivity changes. This approach led to the discovery of RNATs that control the expression of glpF (glycerol permease) and glpT (glycerol-3-phosphate permease); expression of both genes increased with increased temperature. Results with mutant RNATs indicate that both genes are controlled at the translational level. Increased import of glycerols at high temperatures could provide thermoprotection to proteins.

Vascular signaling plasticity reprograms neurovascular coupling pathways to precisely match energy delivery to neuronal metabolic needs

Neuronal computation is metabolically expensive and relies on the timely delivery of energy substrates via tightly controlled blood flow to prevent energetic deficits. The range of mechanisms responsible for this coupling of neural activity to blood flow are collectively termed ‘neurovascular coupling’ (NVC). These NVC mechanisms are typically assumed to be invariant and the possibility that they may be plastic, allowing reshaping of energy delivery according to ever-shifting neuronal metabolic needs, has not been considered. We present evidence that neuronal activity resculpts blood flow control mechanisms inherent to the endothelium, which forms the inner lining of all blood vessels, through a process we refer to as vascular signalling plasticity (VSP). Using an environmental enrichment paradigm, we find that housing mice in an environment that increases input to the barrel cortex drives profound synaptic plasticity within this network. This is accompanied by a remarkable resculpting of local vascular reactivity, augmenting the efficacy of mechanisms that signal for an increase in blood flow. This increase in sensitivity manifests as an increase red blood cell flux to capillary stimulation with extracellular K+, which activates strong inward rectifier K+ (Kir2.1) channel-dependent capillary-to-arteriole electrical signalling to elicit hyperemia. To support this augmentation, we find that VSP induces a ~70% increase in the density of Kir2.1 channels in endothelial cells membranes which is underlain by transcriptional and translational changes in capillary ECs. Using an ex vivo capillary-arteriole preparation, we demonstrate that this increase in membrane Kir2.1 channels translates into a profound shift in the sensitivity of capillaries to K+ stimulation to evoke upstream arteriolar dilation. Together, these results suggest that increasing neuronal energy consumption leads to a profound potentiation of the retrograde hyperpolarization generated by the endothelium during activity, enhancing upstream dilation at the penetrating arteriole and augmenting blood delivery to match enhanced local needs. Our data thus recast the capillary bed as a plastic, brain-wide, neural activity sensing network that is modulated at the molecular level by local neural input. This allows fine-tuning of existing blood delivery mechanisms to meet continually fluctuating neural energy needs. VSP represents a novel facet of brain plasticity that may be utilised by various physiological processes and may be disrupted in aging and in the broad range of brain pathologies that have a vascular component. Support for this work was provided by the NIH National Institute on Aging and National Institute of Neurological Disorders and Stroke (1R01AG066645, 5R01NS115401 [PI: S. Sakadžić], and 1DP2NS121347-01, to T.A.L), the American Heart Association (Awards 17SDG33670237 and 19IPLOI34660108 to T.A.L) and an NIH S10 grant (S10 OD026698, to University of Maryland School of Medicine CIBR Core Confocal Facility). This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Sulfonamide derived from anacardic acid as potential antichagasic: a theoretical approach based on molecular docking, molecular dynamics, and density functional theory calculations.

Chagas disease (CD) is a tropical disease caused by the parasite Trypanosoma cruzi, transmitted by the barber insect. Currently, there are approximately 7 million infected people in the world, and it is estimated that 70 million people could contract this disease. The anacardic acid (AA) showed effectiveness in in silico and in vitro tests. The antichagasic potential of five sulfonamide molecules, derived from anacardic acid, was evaluated from a molecular approach based on the density functional theory (DFT), molecular dynamics (MD), and molecular docking (docking) calculations. Methyl 2-methoxy-6- (8- (methylsulfonamide) octyl) benzoate (SA1); 2-methoxy-6- (8- (phenylsulfonamide) octyl) benzoate (SA2); methyl 2-methoxy-6- (8- (2methylphenyl sulfonamide) octyl) benzoate (SA3); methyl 2-methoxy-6- (8-(methylphenylsulfonamide)octyl)benzoate (SA4); methyl2-(8-(2,5-dimethylphenylsulfonamide)octyl)-6-methoxybenzoate (SA5) were the investigated molecules. The DFT calculations were performed using the B3LYP/6-311+G (d, p) level of theory. The global and local reactivity data showed that SA1 shows the highest molecular reactivity, while SA2 is the most stable derivative. In addition, the structures of investigated molecules were confirmed by the linear correlations higher than 0.98 displayed between the experimental and calculated spectroscopic data (IR and NMR). Molecular docking of the molecules showed a greater prominence for the SA1, SA2, and SA4 molecules in the results of distances of ligand-cruzain. In molecular dynamics, SA2 obtained better stability due to greater interactions with important amino acids of cruzain.

Inhibitory behavior and adsorption of asparagine dipeptide amino acid on the Fe(111) surface.

The inhibitory effect of asparagine (Asn) and its derivatives on iron (Fe) corrosion was studied by performing density functional theory (DFT) calculations. In this paper, the global and local reactivity descriptors of Asn in the protonated and neutral forms were evaluated. Also, the changes in reactivity were investigated when dipeptides were combined with Asn. Due to the increase in the reaction centers within their molecular structure, there was an enhancement in the inhibitory effect of these dipeptides. Moreover, the adsorption energies (Eads) and the adsorption configurations of Asn and small peptides (SPs) with most stability were determined on the surface of Fe(111). It was found that dipeptides had a chemical adsorption on these substrates. In the protonated forms, there was an enhancement in the absolute values of Eads between the inhibitors and the Fe(111) surfaces. Peptides were more likely to be adsorbed on the Fe surfaces, showing the great inhibitory effect of these moieties. The results of the current research demonstrate the possibility of utilizing SPs as efficient "green" corrosion inhibitors. DFT computations were undertaken by employing the BIOVIA Material Studio with B3LYP-D3 functional and 6-31 + G* basis set. The theoretical evaluation of the inhibitory effect of asparagine (Asn) dipeptides, and the potential analysis of small peptides to protect against the corrosion of Fe, was done.

Synthesis, non-covalent interactions and chemical reactivity of 1-pentyl-3-phenylquinoxalin-2(1H)-one — Structural and computational studies

This contribution presents the synthesis of a new quinoxaline derivative, 1-pentyl-3-phenylquinoxalin-2(1H)-one with formula C19H20N2O, through an alkylation reaction, followed by a thorough structural characterization. X-ray crystallography revealed that π-stacking and unconventional CH…O/π hydrogen bonding play a significant role in the supramolecular solid-state framework. These interactions are further assisted by infrequent CO…π interactions and CH…HC dispersive contacts. These non-covalent interactions (NCIs) are analyzed in terms of geometrical criteria, and Hirshfeld surface analysis is used to demonstrate their individual contributions. The nature and strength of prevalent NCIs are thoroughly discussed via computational tools NCI, NBO, and QTAIM. Moreover, the application of Density Functional Theory (DFT) at the wB97X-D/cc-pVTZ level yields valuable insights into both the global and local chemical reactivity of studied compound, thereby enhancing our understanding of the chemistry involved in the synthesis of quinoxaline and its derivatives.

High-Spatiotemporal-Resolution Electrochemical Measurements of Electrocatalytic Reactivity

The real-time measurement of the individual or local electrocatalytic reactivity of catalyst particles instead of ensemble behavior is considerably challenging but very critical to uncover fundamental insights into catalytic mechanisms. Recent remarkable efforts have been made to the development of high-spatiotemporal-resolution electrochemical techniques, which allow the imaging of the topography and reactivity of fast electron-transfer processes at the nanoscale. This Perspective summarizes emerging powerful electrochemical measurement techniques for studying various electrocatalytic reactions on different types of catalysts. Principles of scanning electrochemical microscopy, scanning electrochemical cell microscopy, single-entity measurement, and molecular probing technique have been discussed for the purpose of measuring important parameters in electrocatalysis. We further demonstrate recent advances in these techniques that reveal quantitative information about the thermodynamic and kinetic properties of catalysts for various electrocatalytic reactions associated with our perspectives. Future research on the next-generation electrochemical techniques is anticipated to be focused on the development of instrumentation, correlative multimodal techniques, and new applications, thus enabling new opportunities for elucidating structure-reactivity relationships and dynamic information at the single active-site level.

Computational evaluation on molecular stability and binding affinity of methyldopa against Lysine-specific demethylase 4D Enzyme through quantum chemical computations and molecular docking analysis

For the complete characterization of the molecule, quantum chemical calculations utilizing density functional theory (DFT) were performed at the B3LYP/6–311++G(d,p) level of theory. The quantum theory of atoms in molecules (QTAIM) and the reduced density gradient (RDG) analysis were implemented to investigate non-covalent interactions. The electronic environment of each atom in a molecule was explored using an electron localization function (ELF). Molecular stability of dimer structure due to intermolecular hydrogen bonds: O29-H54⋅⋅⋅O2, O1-H26⋅⋅⋅O30, and O32-H56⋅⋅⋅O4 and their corresponding stabilization energies were predicted by natural bond orbital (NBO) analysis. The energy gap and global and local reactivity parameters were determined to predict the chemical reactivity. The molecular electrostatic potential (MEP) was used to predict the electrophilic and nucleophilic sites. The frontier molecular orbitals (FMOs) were also portrayed using a density of states (DOS). Molecular docking was performed to study the interaction of the molecule with an enzyme, Lysine-specific demethylase 4D-like, a human protein.

Local reactivity descriptors of the important atoms in chelotropic reactions provide insight into their global variants along the reaction path

AbstractChelotropic reactions are widely used in organic synthesis. These reactions are of the pericyclic type where a π bond and a lone pair are transformed into a pair of sigma bonds; with both sigma bonds added to the same atom. This work presents an analysis of several representative chelotropic reactions. To study the reaction path, we have divided it into two parts, from the reactants to the transition state and from the transition state to the products which has allowed us to compare the behavior of the reactants in these two ranges of the path. To perform the analysis, global reactivity descriptors based on the conceptual‐density functional theory (DFT), such as electrophilicity and global softness, have been calculated. To analyze these descriptors, the corresponding local descriptors have been used. A model based on Sanderson's principle (electronegativity equalization principle), developed previously, has been used to calculate the local reactivity descriptors (atomic). The statistical methodology of multiple regression analysis has been used to determine which local variables are the most relevant for the global parameter under study (softness, and electrophilicity), also the principal component analysis has been used as a guide to estimate the number of variables to take into account in the analysis, finally this has led us to important correlations between global and local parameters which has allowed us to analyze the reactions of the study. Transition states of the reactions are aromatic as obtained from the nucleus independent chemical shift (NICS) and gauge including magnetically induced ring current (GIMIC) analysis.

Operando Scanning Electrochemical Probe Microscopy during Electrocatalysis.

Scanning electrochemical probe microscopy (SEPM) techniques can disclose the local electrochemical reactivity of interfaces in single-entity and sub-entity studies. Operando SEPM measurements consist of using a SEPM tip to investigate the performance of electrocatalysts, while the reactivity of the interface is simultaneously modulated. This powerful combination can correlate electrochemical activity with changes in surface properties, e.g., topography and structure, as well as provide insight into reaction mechanisms. The focus of this review is to reveal the recent progress in local SEPM measurements of the catalytic activity of a surface toward the reduction and evolution of O2 and H2 and electrochemical conversion of CO2. The capabilities of SEPMs are showcased, and the possibility of coupling other techniques to SEPMs is presented. Emphasis is given to scanning electrochemical microscopy (SECM), scanning ion conductance microscopy (SICM), electrochemical scanning tunneling microscopy (EC-STM), and scanning electrochemical cell microscopy (SECCM).

Electron Tunneling at Electrocatalytic Interfaces

It was recently proposed that tunneling current fluctuations in electrochemical scanning tunneling microscopy (EC-STM) can be used to map the electrocatalytic activity of surfaces with high spatial resolution. However, the relation between the increased noise in the electron tunneling signal and the local reactivity for such complex electrode/electrolyte interfaces is only explained qualitatively or hypothetically. Herein, we employ electron transport calculations to examine tunneling at Pt surfaces under the conditions of the oxygen reduction reaction as a case study. By computing current–voltage characteristics, we reveal that the tunneling barrier strongly depends on the chemical identity of the adsorbed reaction intermediate as well as on the orientation of the average dipole moment of water species mediating electron tunneling. Our theoretical results combined with EC-STM measurements suggest that detecting reaction intermediates at electrified interfaces in operando conditions is possible based on tunneling noise amplitudes. This study also aims to stimulate further explorations of tunneling-based electron-proton transfers to enable quantum electrocatalysis beyond conventional approaches.