Bottlenecks in the prediction of regioselectivity of [4 + 2] cycloaddition reactions: an assessment of reactivity descriptors

B3LYP/6-31G(d) calculations were performed to obtain all the transition states and products for the 128 distinct reaction channels of Diels-Alder reactions by taking all possible combinations from a series of dienes (1N-a, 1N-b, 2N, 1P-a, 1P-b, 2P, 1O, 1S) and dienophiles (NE, PE, OE, SE, AE, OHE, MeE, CNE). The predictive ability of the values to gauge the regioselectivity of the putative [4 + 2] cycloaddition reactions is analysed. No correlation is obtained between the reaction energies and activation energies. The extent of asynchronicity is measured based on the bond order analysis. DFT-based descriptors such as the local softness (sk+ and sk−), Fukui function indices (fk+ and fk−), global electrophilicity index (ω) and local electrophilicity index (ωk) were found to be better than the conventional FMO predictions

Feasibility of carbon nanomaterials as gas sensors: a computational study

Carbonaceous materials are a promising class of materials for potential application as chemical and biomolecule sensors. In this work we have done first principles calculations to study the interaction of various small molecules, such as CO2, H2O, NH3, CH4 and H2, on the surface of carbon nanotubes (CNTs) and graphene in order to study their feasibility as gas sensors. Model systems for armchair and zigzag CNTs of different diameter have been considered to study the effect of chirality and curvature of the carbon nanomaterials on binding with these small molecules. Our results reveal that these gas molecules have been weakly physisorbed on the surface and act as charge donors to the carbon nanomaterials. Charge transfer between the gas molecules and the carbon materials impacts the physical properties of the carbon materials, which may be traced to their sensitivity. As the gas molecules are physisorbed on the carbon materials, they may be suitable for repetitive sensor operation. Significant changes in the polarizability of the carbon materials have been observed on binding with the gas molecules and monitoring such changes provides valuable guidance in designing optimal gas sensors based on carbon materials that could satisfy the demand in various fields

Measures to evaluate heteroaromaticity and their limitations: story of skeletally substituted benzenes

Ab initio HF, MP2, CCSD(T) and hybrid density functional B3LYP calculations were performed on a series of skeletally mono- and di-substituted benzenes, (CH)5Z and (CH)4Z2, Z = C-, N, O+, Si-, P, S+, Ge-, As, Se+, BH-, NH+, AlH-, SiH, PH+, GaH-, GeH and AsH+. Various measures of aromaticity such as the bond length equalization, homodesmic equations, singlet-triplet energy difference (DEs-t), chemical hardness (η) and out-of-plane distortive tendency are critically analysed. The relative energy ordering in skeletally disubstituted benzenes displays trends that are inexplicable based on conventional wisdom. In general, the orthoisomer is found to be the least stable when the substituent is from the second row, whereas if the substituent is from the fourth row, the ortho-isomer is the most stable. Various qualitative arguments, including (a) lone pair-lone pair repulsion, (b) the sum of bond strengths in the twin Kekule forms, and (c) the rule of topological charge stabilization (TCS), are used to explain the observed relative energy trends. The rule of TCS in conjunction with the sum of bond strengths is found to predict the relative energy ordering reasonably well. The reactivity of this class of compounds is assessed based on their singlet-triplet energy differences, chemical hardness and the frequencies corresponding to out-of-plane skeletal distortions. These reactivity indices show less kinetic stability for the compounds with substituents from the fourth row and point to the fact that the thermodynamically most stable compounds need not be the least reactive ones. The Δ Es-t values indicate that the Π-framework of benzene weakens upon skeletal substitutions

Specificity rendering ‘hot-spots’ for aurora kinase inhibitor design: the role of non-covalent interactions and conformational transitions

The present study examines the conformational transitions occurring among the major structural motifs of Aurora kinase (AK) concomitant with the DFG-flip and deciphers the role of non-covalent interactions in rendering specificity. Multiple sequence alignment, docking and structural analysis of a repertoire of 56 crystal structures of AK from Protein Data Bank (PDB) has been carried out. The crystal structures were systematically categorized based on the conformational disposition of the DFG-loop [in (DI) 42, out (DO) 5 and out-up (DOU) 9], G-loop [extended (GE) 53 and folded (GF) 3] and αC-helix [in (CI) 42 and out (CO) 14]. The overlapping subsets on categorization show the inter-dependency among structural motifs. Therefore, the four distinct possibilities a) 2W1C (DI, CI, GE) b) 3E5A (DI, CI, GF) c) 3DJ6 (DI, CO, GF) d) 3UNZ (DOU, CO, GF) along with their co-crystals and apo-forms were subjected to molecular dynamics simulations of 40 ns each to evaluate the variations of individual residues and their impact on forming interactions. The non-covalent interactions formed by the 157 AK co-crystals with different regions of the binding site were initially studied with the docked complexes and structure interaction fingerprints. The frequency of the most prominent interactions was gauged in the AK inhibitors from PDB and the four representative conformations during 40 ns. Based on this study, seven major non-covalent interactions and their complementary sites in AK capable of rendering specificity have been prioritized for the design of different classes of inhibitors

Anomalous lithium adsorption propensity of monolayer carbonaceous materials: a density functional study

Interaction between lithium and carbonaceous materials has gained a lot of importance in lithium battery industry as an important source of energy and storage. The size, dimension, curvature and chirality of the carbonaceous materials are found to be very important factors in controlling the sequential binding of lithium. The propensity of lithium binding to the monolayer carbonaceous materials has been studied using Density functional theory (DFT). Structural and energetical parameters of the complexes have been analyzed through interaction energy, sequential energy, Mulliken population analysis and spin density distribution. Spindensity of odd Li doped systems reveals the preferences for addition of further lithium atoms on the surface. Upon analyzing the interaction energy in armchair carbon nanotubes (A-CNTs) and zigzag carbon nanotubes (Z-CNTs), it has been observed that external and internal surfaces of CNTs have contrasting binding preferences for sequential addition of Li atoms. Internal surface is found to be more feasible site for lithium adsorption than the external surface. This current study provides fundamental understanding of the mechanism of lithium adsorption in lithium battery

Dynamic ligand-based pharmacophore modeling and virtual screening to identify mycobacterial cyclopropane synthase inhibitors

Multidrug resistance in Mycobacterium tuberculosis (M. Tb) and its coexistence with HIV are the biggest therapeutic challenges in anti-M. Tb drug discovery. The current study reports a Virtual Screening (VS) strategy to identify potential inhibitors of Mycobacterial cyclopropane synthase (CmaA1), an important M. Tb target considering the above challenges. Five ligand-based pharmacophore models were generated from 40 different conformations of the cofactors of CmaA1 taken from molecular dynamics (MD) simulations trajectories of CmaA1. The screening abilities of these models were validated by screening 23 inhibitors and 1398 non-inhibitors of CmaA1. A VS protocol was designed with four levels of screening i.e., ligand-based pharmacophore screening, structure-based pharmacophore screening, docking and absorption, distribution, metabolism, excretion and the toxicity (ADMET) filters. In an attempt towards repurposing the existing drugs to inhibit CmaA1, 6,429 drugs reported in DrugBank were considered for screening. To find compounds that inhibit multiple targets of M. Tb as well as HIV, we also chose 701 and 11,109 compounds showing activity below 1 μM range on M. Tb and HIV cell lines, respectively, collected from ChEMBL database. Thus, a total of 18,239 compounds were screened against CmaA1, and 12 compounds were identified as potential hits for CmaA1 at the end of the fourth step. Detailed analysis of the structures revealed these compounds to interact with key active site residues of CmaA1

2D-Double transition metal MXenes for spintronics applications: surface functionalization induced ferromagnetic half-metallic complexes

MXenes are rapidly emerging two-dimensional (2D) materials with thickness, composition, and functionalization-dependent outstanding properties having applications in diverse fields. To disclose nano-spintronic applications of 2D-double transition metal (DTM) carbide and nitride-based pristine and surface-functionalized MXenes (M'2M"X2Tx, M' and M" = Cr, Mo, W; X = C/N; T = -F/-OH/=O), a systematic investigation has been performed on structural stability, magnetic properties and electronic structure using spin-polarized first-principles calculations. 36 stables functionalized MXenes were screened from 144 explored DTM based MXenes. The explored materials exhibit striking properties, having wide range of magnetic ground states, from non-magnetic to ferromagnetic, and then to antiferromagnetic, accompanied by metallic to half-metallic or gapless half-metallic properties, depending on transition metal(s) and terminating group. Mo and W-based MXenes are found to be nonmagnetic and metallic, whereas Cr-Mo and Cr-W-based MXenes are magnetic with varying metallic behavior. W2CrN2O2 and Mo2CrN2O2 systems are found to be ferromagnetic half-metallic 2D materials with a direct band gap of 1.35 eV and 0.77 eV respectively, in the minority spin channel. The comprehensive study on DTM MXenes, provide intrinsic half-metallic properties along with robust ferromagnetism, opens up a class of promising new 2D materials with tunable magnetic and electronic properties for potential device applications in nano-spintronics and electronics.Comment: 61 pages, 6 figures, S

The bicyclo[2.1.1]hexan-2-one system: a new probe for the experimental and computational study of electronic effects in π-facial selectivity in nucleophilic additions

The remotely substituted 5-exo-bicyclo[2.1.1]hexan-2-one system is introduced as a new probe to study long range electronic effects on π -face selectivity during hydride reduction and a systematic computational study demonstrates good predictability at the semi-empirical level

Structure-function relationships among selected human coronaviruses

536-551Identifying the key proteins among different types of human disease-causing coronaviruses is essential for the molecular mechanism and thereby designing potential drug molecules. Eight selected proteins of seven types of disease-causing coronaviruses, viz.SARS-CoV-2 (severe acute respiratory syndrome coronavirus2), SARS-CoV (severe acute respiratory syndrome coronavirus), MERS-CoV (middle east respiratory syndrome coronavirus), Human coronavirus OC43, Human coronavirus HKU1, Human coronavirus 229E and Human coronavirus NL63, were chosen for the comparison. Further, an attempt has been made to explore the most important host-pathogen interactions with a special focus on spike (RBD) protein region as this region deemed to be functionally most important. Epitope region was also identified which helps in the design of epitope-based vaccines. The structural comparison carried out among the seven types of human coronaviruses has revealed the molecular level details on the similarity among this series. This study has facilitated the identification of the important residues in the studied proteins which control the key functions such as viral replication and transmission. Thus, exploring the protein space in the family of coronaviruses, provide valuable insights into the molecular basis associated with the role of proteins and viral infections, which is expected to trigger the identification of the drug targets for coronaviruses infections, in a rational way

Computational studies on siblings en-route to fullerenes: study of curved polycyclic aromatic hydrocarbons

Computational studies at ab initio, DFT and semiempirical levels were carried out on a large number of buckybowl molecules. Corannulene 2 and Sumanene 3 constitute the primary buckybowls as they are readily identifiable C<SUB>60</SUB> fragments along the C<SUB>5</SUB> and C<SUB>3</SUB> axes, respectively. These studies are directed at understanding the most elegant strategy to modulate the curvature of buckybowl molecules. The importance of choosing the right precursor for the successful synthesis of the target buckybowl molecules were highlighted. The effect of sequential ring annelation to the rim of buckybowl on their structures, curvature and inversion dynamics were studied. The energy profiles of the substituted buckybowls were fit to a double-well potential, which results in an empirical correlation between the bowl-to-bowl inversion and the bowl depths. The effect of metal ion binding to the concave and convex surfaces of the bowl structure and the inversion dynamics was also studied