MD, DFT Investigations and Inhibition of the Novel SARS- CoV-2 Mainprotease in Three Cocrystals of Hydrochloro- thiazide

In crystal engineering and medicinal chemistry, cocrystals have enormous applications. Hydrochlorothiazide (HTZ) is found to form cocrystals with picolinic acid (HCP1), pyrazinamide (HPP2) and isonicotinic acid (HIP3). In order to predict energy properties and model potential charge transfer between cocrystal constituents, FMOs energies are used. The frontier molecular orbital analysis reveals the cocrystal’s chemical reactivity and bioactivity. MEP displays the different reactive surfaces in the cocrystals, which is very important when deciding on different biological activities. HCP1, HPP2 and HIP3 have different intermolecular interactions, most of the bonds between atoms are covalent and some of the intramolecular interactions are strong ionic or weak ionic. The non-covalent interactions and identical patterns in the covalent character of weak interactions in title molecules are supported by ELF and LOL. From the MD simulation, the complex structure formed by the HIP3 compound with Mpro was more stable and lower RMSD values than HCP1 and HPP2. The ligands formed strong interactions at SARS-Cov-2 Mpro possible binding sites.</p

DFT, docking, MD simulation, and vibrational spectra with SERS analysis of a benzoxazole derivative: an anti-cancerous drug

Spectroscopic, DFT, and SERS studies of antimicrobial bioactive 2-(p-bromophenyl)-5-(2-(4-(p-chlorophenyl)piperazine-1-yl)acetamido)benzoxazole (BCAB) have been reported. Very large changes are seen wavenumbers in Raman and SERS. Variations in modes may be due to surface pi-electron interactions and means, the BACB is inclined with respect to the metal surface. Theoretical molecular geometry optimization parameters, wavenumbers, frontier molecular orbitals, and molecular electrostatic potential surface have been calculated using density functional theory. The docked ligand forms a stable complex with SOCS-2 and can be BCAB may be an anti-cancerous drug. According to RMSD, RMSF, and Rg analysis, BACB and SOCS-2 protein form a stable and stable interaction

The concentration dependent SERS studies of a bioactive 4-chlorobenzylidene derivative: Experimental and DFT investigations

In this work, the vibrational spectroscopy of the compound (E)-4-(tert-butyl)-Nˈ-(4-chlorobenzylidene)benzyhydrazide (TCB), which was studied in conjunction with theoretical calculations, is applied for Surface Enhanced Raman Scattering (SERS) studies. The assignments of the vibrational modes were completed with Density Functional Theory (DFT)/B3LYP/6-311++G*. The information gathered is utilized to determine the chemical and electrical characteristics in addition to wavenumber measurements. The TCB molecule's chemisorbed status on colloidal nanoparticles is confirmed by acquired red shift and decreased intensity behavior in the UV–VIS spectrum analysis. Additionally, the SERS spectra at varied concentrations and the chemisorption of the molecule with metal cluster were recorded and examined. Additionally, a silver cluster-based theoretical SERS model is put forth. The findings presented here will help in the construction of more dependable SERS sensors by thoroughly describing the concentration-dependent profile of analyte orientation

Theoretical investigation on the reactive and interaction properties of sorafenib – DFT, AIM, spectroscopic and Hirshfeld analysis, docking and dynamics simulation

© 2021 Elsevier B.V.Hepatocellular carcinoma is one of the severe types of malignancy characterized by rapid tumor growth and is mostly found in the last stage of very advanced tumor formation. In this manuscript, we present the gross structural features of sorafenib and its reactivity and wavefunction properties using computational simulations. Density functional theory was used to optimize the ground state geometry and docking was used to predict biological activity. Various intermolecular interactions are analyzed and reaction sites for attacking electrophiles and nucleophiles identified. The calculated values of electron density, Laplacian and ellipticity for all bonds designated the formation of an ionic or covalent bond. Regions between carbon and nitrogen have high LOL values showing covalent bond nature. Molecular docking and dynamics simulations studies show that from the binding energy, RMSD, RMSF and Rg analysis of sorafenib and multidrug resistance-associated protein 1 forms a stable and stable interaction

DFT, molecular docking and SERS (concentration and solvent dependant) investigations of a methylisoxazole derivative with potential antimicrobial activity

Spectroscopic analysis, DFT studies and surface enhanced Raman scattering of antimicrobial bioactive 4-[(2\u2011hydroxy-3,5-diiodobenzylidene)amino]-N-(5-methylisoxazole-3-yl)benzenesulfonamide (HDMB) have been studied. Changes in intensity and enhancement variations are observed for Raman and SERS bands. Changes observed in the ring mode vibrations may be due to surface \u3c0-electron interactions which means molecule is orientated in a tilted position with respect to metal surface. Changes in orientation are seen in SERS spectra depending on concentration. The molecular docking results show that binding affinity and interactions with the receptors may be supporting evidence for further studies in design further HDMB pharmaceutical applications. Reactivity properties are obtained from DFT analysis

Modeling the structural and reactivity properties of hydrazono methyl-4H-chromen-4-one derivatives-wavefunction-dependent properties, molecular docking, and dynamics simulation studies.

This study explains the vibration and interaction of three pharmaceutically active hydrazine derivatives, (E)-3-((2-(2,5-difluorophenyl)hydrazono)methyl)-4H-chromen-4-one (DFH), (E)-3-((2-(4-(trifluoromethyl)phenyl)hydrazono)methyl)-4Hchromen-4-one (TMH), and (E)-3-((2-(3,5-bis(trifluoromethyl)phenyl)hydrazono)methyl)-4H-chromen-4-one (BPH) using theoretical approach. The trend in chemical reactivity and stability of the studied compounds was observed to show increasing stability and decreasing reactivity and this was obtained from orbital energies. The effect of bromine and chlorine atoms, instead of fluorine atoms, is also noted. Surface analysis on the covalent bond was attained by ELF and LOL analysis. Biological activities were predicted using molecular docking studies. Docking results were analyzed with standard drugs, 5-fluorouracil/piperine. Antitumor activity of hydrazine derivativeswas found to be higher than reference ones. Molecular dynamics (MD) simulation was performed for 100 ns to validate the stability behavior of hydrazine derivatives with the dual specificity threonine tyrosine kinase (TTK) protein. RMSD, RMSF, Rg, SASA, and intermolecular analysis of DFH, TMH, and BPH with threonine tyrosine kinase forms stable ligand-protein interactions. The molecular and predictive biological properties of three pharmaceutically active hydrazine derivatives which can be helpful to researchers in future experimental validation through in vitro and in vivo studies

DFT, SERS-concentration and solvent dependent and docking studies of a bioactive benzenesulfonamide derivative

Spectroscopic analysis, DFT studies and surface enhanced Raman scattering (SERS) of antimicrobial bioactive 4-[(5-tert-butyl)2-hydroxybenzylidene]amino-N-(4,6-dimethylpyrimidin-2-yl)benzenesulfonamide (THPB) have been studied on different silver sols. Intensity and hence enhancement variations are observed for Raman and SERS bands. Observed changes in the ring modes may be due to surface π-electron interactions and presence of this indicated that molecule is inclined with respect to the metal surface. Changes in orientation are seen in SERS spectra depending on concentration. The molecular docking results show that binding affinity and interactions with the receptors may be supporting evidence for further studies in design further THPB pharmaceutical applications. Reactivity properties are obtained from DFT analysis

An investigation on spectroscopic, wavefunction dependent reactivity, docking and anti-Covid-19 ability of flupentixol dihydrochloride: DFT and MD simulations at different temperatures

A detailed vibrational analysis of flupentixol dihydrochloride (FDC) is performed by Density Functional Theory (DFT) calculations. Wavefunction reactivity properties and Atoms In Molecules (AIM) analysis are also performed. There is enormous O1-H1B…Cl1, N1-H1A…Cl1 and C9-H9A…F3B intermolecular hydrogen bonding in FDC. Electrons were resonated on the aromatic rings without any interference with aliphatic moiety of both highest occupied molecular orbital (HOMO) and in least unoccupied molecular orbital (LUMO) which is due to participation of fluorine atom intermolecular hydrogen bonding with adjacent C–H. The electron localization function (ELF) shows under populated N-C single bonds of ring A owing to the strong electron withdrawing effect of nitrogen atoms. SARS-CoV-2 main protease with FDC had energy −80 kcal/mol. With the help of molecular dynamics (MD), radial distribution functions (RDF) are calculated to identify the most critical interaction with water molecules

Spectroscopic, quantum mechanical studies, ligand protein interactions and photovoltaic efficiency modeling of some bioactive benzothiazolinone acetamide analogs

YALCIN, Gozde/0000-0002-9689-2239; Thomas, Renjith/0000-0003-0011-633X; yildiz, ilkay/0000-0001-9526-0232WOS: 000505358200002In the present work, the molecules, N-(4-chlorophenyl)-2-[6-(benzoyl)-2-benzothiazolinone-3-yl]acetamide (CBBA), N-(6-methyl-2-pyridyl)-2-[6-(2-chlorobenzoyl)-2-benzothiazolinone-3-yl]acetamide (MCBA), N-(3-Chlorophenyl)-2-[6-(2-fluorobenzoyl)-2-benzothiazolinone-3-yl]acetamide (CFBA) and N-(6-methyl-2-pyridyl)-2-[6-(2-fluorobenzoyl)-2-benzothiazolinone-3-yl]acetamide (MFBA) have been synthesized followed by the study of vibrational spectra and electronic properties. Photochemical and thermochemical modeling of the title compounds is also performed to analyze its ability to be used as phtosensitizers in dye-sensitized solar cells (DSSCs) and the compounds are found to show good light harvesting efficiency (LHE) and good free energy of electron injection to be used in the photo-voltaic cells. the non-linear optical (NLO) activity of the compounds has been investigated and second-order hyperpolarizability values vary in the order CFBA > CBBA > MCBA > MFBA. Natural bond orbital analysis provided insights into the various possible intramolecular interactions. Molecular docking has been accomplished by the Schrodinger suite to understand the binding interactions of the analyzed ligands with Cyclooxygenase 1 (COX1). Molecular docking studies indicated that compound MFBA had the best binding affinity