Evaluating the Anticancer Properties of Novel Piscidinol A Derivatives: Insights from DFT, Molecular Docking, and Molecular Dynamics Studies.

Cancer is characterized by uncontrolled cell growth and spreading throughout the body. This study employed computational approaches to investigate 18 naturally derived anticancer piscidinol A derivatives (-) as potential therapeutics. By examining their interactions with 15 essential target proteins (HIF-1α, RanGAP, FOXM1, PARP2, HER2, ERα, NGF, FAS, GRP78, PRDX2, SCF complex, EGFR, Bcl-xL, ERG, and HSP70) and comparing them with established drugs such as camptothecin, docetaxel, etoposide, irinotecan, paclitaxel, and teniposide, compound emerged as noteworthy.

Investigating the potential of 6-substituted 3-formyl chromone derivatives as anti-diabetic agents using in silico methods.

In exploring nature's potential in addressing diabetes-related conditions, this study investigates the therapeutic capabilities of 3-formyl chromone derivatives. Utilizing in silico methodologies, we focus on 6-substituted 3-formyl chromone derivatives (1-16) to assess their therapeutic potential in treating diabetes. The research examined the formyl group at the chromone's C-3 position.

Design, synthesis, and bioevaluation of novel unsaturated cyanoacetamide derivatives: In vitro and in silico exploration.

In this study, we synthesized novel α,β-unsaturated 2-cyanoacetamide derivatives () using microwave-assisted Knoevenagel condensation. Characterization of these compounds was carried out using FTIR and H NMR spectroscopy. We then evaluated their in vitro antibacterial activity against both gram-positive and gram-negative pathogenic bacteria.

Accelerating the discovery of the beyond rule of five compounds that have high affinities toward SARS-CoV-2 spike RBD.

The battle against SARS-CoV-2 coronavirus is the focal point for the global pandemic that has affected millions of lives worldwide. The need for effective and selective therapeutics for the treatment of the disease caused by SARS-CoV-2 is critical. Herein, we performed a hierarchical computational approach incorporating molecular docking studies, molecular dynamics simulations, absolute binding energy calculations, and steered molecular dynamics simulations for the discovery of potential compounds with high affinity towards SARS-CoV-2 spike RBD.

High-throughput virtual screening of drug databanks for potential inhibitors of SARS-CoV-2 spike glycoprotein.

COVID-19, which is caused by a novel coronavirus known as SARS-CoV-2, has spread rapidly around the world, and it has infected more than 29 million individuals as recorded on 16 September 2020. Much effort has been made to stop the virus from spreading, and there are currently no approved pharmaceutical products to treat COVID-19. Here, we apply an approach to investigate more than 3800 FDA approved drugs on the viral RBD S-ACE2 interface as a target.

Discovery of potent inhibitors for SARS-CoV-2's main protease by ligand-based/structure-based virtual screening, MD simulations, and binding energy calculations.

COVID-19 has caused lockdowns all over the world in early 2020, as a global pandemic. Both theoretical and experimental efforts are seeking to find an effective treatment to suppress the virus. In silico drug design can play a vital role in identifying promising drug candidates against COVID-19.

Molecular level investigation of curcumin self-assembly induced by trigonelline and nanoparticle formation.

Nanoparticle-facilitated drug delivery forms the core of medicine nowadays with the drug being delivered right at the target, reducing side effects and enhancing therapeutic value. Nanoparticles derived from natural compounds are further a point of focus being biocompatible and safe by and large. In this study, we have performed HF/6-31G calculations coupled with intermolecular interaction calculations and nanoscale molecular dynamics simulations to investigate self-assemblage in curcumin induced by trigonelline.

Direct Observation of an Oxepin from a Bacterial Cytochrome P450-Catalyzed Oxidation.

The cytochromes P450 are hemoproteins that catalyze a range of oxidative C-H functionalization reactions, including aliphatic and aromatic hydroxylation. These transformations are important in a range of biological contexts, including biosynthesis and xenobiotic biodegradation. Much work has been carried out on the mechanism of aliphatic hydroxylation, implicating hydrogen atom abstraction, but aromatic hydroxylation is postulated to proceed differently.

Computational study on thermochemical properties for perhalogenated methanols (CX3OH) (X = F, Cl, Br).

The perhalogenated methanols (CX3OH; X = F, Cl, and Br) are found in the atmosphere as products of the degradation of halocarbons. The thermochemical properties for these molecules have been calculated at the HF, MP2, and B3LYP levels of theories in conjunction with six different basis sets as well as at G3MP2 and CBS-QB3. Calculated properties include the gas-phase enthalpies of formation (ΔfH(0)), gas-phase acidities (ΔacidG(0)), gas-phase proton affinity, and bond dissociation energies of the C-O and O-H bonds of CX3OH.

Mechanistic study of the deamidation reaction of glutamine: a computational approach.

Glutamine--a popular nutritional supplement, non-toxic amino acid, and an essential interorgan and intercellular ammonia transporter--can destroy the neurons' mitochondria. When glutamine enters (like a Trojan horse) into the mitochondria, in the presence of glutaminase, it reacts with water and yields glutamate and excess ammonia which opens gates in the membrane of the mitochondria and thereby destroys it. The mechanistic details underlying the molecular basis of the catabolic production of excess ammonia remain unclear.

Comparisons of computational and experimental thermochemical properties of α-amino acids.

This study provides comprehensive benchmark calculations for the thermochemical properties of the common α-amino acids. Calculated properties include the proton affinity, gas-phase basicity, protonation entropy, ΔH°(acid), ΔG°(acid), and enthalpies of formation for the protonated and deprotonated α-amino acids. In order to determine the performance at various levels of theory, including density functional methods and composite methods, the calculated thermochemical properties are compared to experimental results.

Theoretical investigation into competing unimolecular reactions encountered in the pyrolysis of acetamide.

Motivated by the necessity to understand the pyrolysis of alkylated amines, unimolecular decomposition of acetamide is investigated herein as a model compound. Standard heats of formation, entropies, and heat capacities, are calculated for all products and transition structures using several accurate theoretical levels. The potential energy surface is mapped out for all possible channels encountered in the pyrolysis of acetamide.

Computational study of the deamination of 8-oxoguanine.

Oxidation of guanine in DNA yields the nucleobase damage product 8-oxoguanine (8-oxoG), whose further oxidation gives other more stable products. In the present study, the mechanism for the deamination of 8-oxoG with H(2)O, 2H(2)O, H(2)O/OH(-), and 2H(2)O/OH(-) and for protonated 8-oxoG (8-oxoGH(+)) with H(2)O has been investigated using ab initio calculations. All structures were optimized at RHF/6-31G(d), MP2/6-31G(d), and B3LYP with the 6-31G(d), 6-31+G(d), 6-31G(d,p), 6-31+G(d,p), and 6-31++G(d.

Theoretical study on the unimolecular decomposition of thiophenol.

The potential energy surface for the unimolecular decomposition of thiophenol (C(6)H(5)SH) is mapped out at two theoretical levels; BB1K/GTlarge and QCISD(T)/6-311+G(2d,p)//MP2/6-31G(d,p). Calculated reaction rate constants at the high pressure limit indicate that the major initial channel is the formation of C(6)H(6)S at all temperatures. Above 1000 K, the contribution from direct fission of the S-H bond becomes important.

Mechanistic study of the deamination reaction of guanine: a computational study.

The mechanism for the deamination of guanine with H(2)O, OH(-), H(2)O/OH(-) and for GuaH(+) with H(2)O has been investigated using ab initio calculations. Optimized geometries of the reactants, transition states, intermediates, and products were determined at RHF/6-31G(d), MP2/6-31G(d), B3LYP/6-31G(d), and B3LYP/6-31+G(d) levels of theory. Energies were also determined at G3MP2, G3MP2B3, G4MP2, and CBS-QB3 levels of theory.

Atoms and bonds in molecules from radial densities.

Radial densities are explored as an alternative method for partitioning the molecular density into atomic regions and bonding regions. The radial densities for atoms in molecules are similar to those of an isolated atom. The method may also provide an alternative to Bragg-Slater radii.

SEST: Simulated Electronic Structure Theory.

A novel approach to empirically modeling the electronic structure of molecules is introduced. The theory is based on relationships between molecular orbital energy components and the average distance between electrons and electrons and nuclei. The electron-electron and electron-nucleus distances are subsequently related to interatomic distances which provides a means for modeling the electronic structure of molecules.

Determining the transition-state structure for different SN2 reactions using experimental nucleophile carbon and secondary alpha-deuterium kinetic isotope effects and theory.

Nucleophile (11)C/ (14)C [ k (11)/ k (14)] and secondary alpha-deuterium [( k H/ k D) alpha] kinetic isotope effects (KIEs) were measured for the S N2 reactions between tetrabutylammonium cyanide and ethyl iodide, bromide, chloride, and tosylate in anhydrous DMSO at 20 degrees C to determine whether these isotope effects can be used to determine the structure of S N2 transition states. Interpreting the experimental KIEs in the usual fashion (i.e.

Mechanisms for the deamination reaction of cytosine with H2O/OH(-) and 2H2O/OH(-): a computational study.

Mechanisms for the deamination reaction of cytosine with H 2O/OH (-) and 2H 2O/OH (-) to produce uracil were investigated using ab initio calculations. Optimized geometries of reactants, transition states, intermediates, and products were determined at MP2 and B3LYP using the 6-31G(d) basis set and at B3LYP/6-31+G(d) levels of theory. Single point energies were also determined at MP2/G3MP2Large and G3MP2 levels of theory.

Comparison of the Standard 6-31G and Binning-Curtiss Basis Sets for Third Row Elements.

Ab initio calculations were carried out for isogyric reactions involving the third row elements, Ga, Ge, As, Se, and Br. Geometries of all the reactants and products were optimized at the HF, MP2, and B3LYP levels of theory using the 6-31G(d) and 6-31G(d,p) basis sets. For molecules containing third row elements geometries, frequencies and thermodynamic properties were calculated using both the standard 6-31G and the Binning-Curtiss (BC6-31G) basis sets.

Addition reaction of adamantylideneadamantane with Br2 and 2Br2: a computational study.

Ab initio calculations were carried out for the reaction of adamantylideneadamantane (Ad=Ad) with Br2 and 2Br2. Geometries of the reactants, transition states, intermediates, and products were optimized at HF and B3LYP levels of theory using the 6-31G(d) basis set. Energies were also obtained using single point calculations at the MP2/6-31G(d)//HF/6-31G(d), MP2/6-31G(d)//B3LYP/6-31G(d), and B3LYP/6-31+G(d)//B3LYP/6-31G(d) levels of theory.

New insights into the bromination reaction for a series of alkenes--a computational study.

Ab initio calculations were carried out for the reaction of Br2 with ethene, propene, isobutene, fluoroethene, chloroethene, (E)-1,2-difluoroethene, and (E)-1,2-dichloroethene. For ethene the calculations were also carried out for the reaction with 2Br2. Geometries were optimized at the HF, MP2, and B3LYP levels using the 6-31G(d) and 6-31+G(d) basis sets where for Br both the standard 6-31G and the Binning-Curtiss bromine basis sets were used.

A new insight into using chlorine leaving group and nucleophile carbon kinetic isotope effects to determine substituent effects on the structure of SN2 transition states.

Chlorine leaving group k(35)/k(37), nucleophile carbon k(11)/k(14), and secondary alpha-deuterium [(kH/kD)alpha] kinetic isotope effects (KIEs) have been measured for the SN2 reactions between para-substituted benzyl chlorides and tetrabutylammonium cyanide in tetrahydrofuran at 20 degrees C to determine whether these isotope effects can be used to determine the substituent effect on the structure of the transition state. The secondary alpha-deuterium KIEs indicate that the transition states for these reactions are unsymmetric. The theoretical calculations at the B3LYP/aug-cc-pVDZ level of theory support this conclusion; i.

Computational study of the reactions of SiH3X (X=H, Cl, Br, I) with HCN.

Ab initio calculations were carried out for the reactions of silane and halosilanes (SiH3X, X=H, Cl, Br, I) with HCN. Geometries of the reactants, transition states, intermediates and products were optimized at HF, MP2, and B3LYP levels of theory using the 6-31G(d) and 6-31G(d,p) basis sets. Energies were also obtained using G3MP2 and G3B3 levels of theory.