Structural Characterization, Spectroscopic Profile, Molecular Docking, ADMET Properties, Molecular Dynamics Simulation Studies, and Molecular Mechanics Generalized Born Surface Area Analysis of 5-(Adamantan-1-yl)-4-butyl-2,4-dihydro-3H-1,2,4-triazole-3-thione as a Potential COX Inhibitor.

Employing a synergistic combination of theoretical density functional theory (DFT) and experimental techniques, we conducted a comprehensive analysis elucidating the structural and pharmacological attributes of 5-(adamantan-1-yl)-4-butyl-2,4-dihydro-3H-1,2,4-triazole-3-thione (5A4BT) as a potent COX inhibitor. The X-ray crystallographic data of 5A4BT showed the pivotal role played by weak interactions, notably π-π and C-H-π interactions, alongside hydrogen bonding, in orchestrating the intricate supramolecular architectures within the crystalline lattice. A quantitative analysis of the arrangement of the crystal structure, as well as both inter- and intramolecular interactions, was conducted using Hirshfeld surfaces and 2D fingerprint plots. Additionally, a comprehensive examination of the IR spectra was undertaken, employing both experimental methods and theoretical DFT techniques, to elucidate the vibrational characteristics of the compound. The strength of intermolecular N-H···S hydrogen bonding and charge transfer within the system was assessed through natural bonding orbital analysis. Moreover, Bader's atoms in molecules theory was employed to estimate the strength of intermolecular hydrogen bonds, revealing strong interactions within the 5A4BT dimer. The title compound exhibited binding affinities of -6.4 and -6.5 kcal/mol for COX1 (PDB 3KK6) and COX2 (1CX2) target proteins, respectively. For the first time, predictions regarding ADMET properties, drug-likeness, and toxicity, including favorable bioavailability, along with 100 ns molecular dynamics simulations, binding free energy, and energy decomposition per residue in the binding cavity of the protein from molecular mechanics generalized born surface area approach, collectively indicate the potential of 5A4BT as a nonselective COX inhibitor.

Spectroscopic, electronic structure, molecular docking, and molecular dynamics simulation study of 7-Trifluoromethyl-1H-indole-2-carboxylic acid as an aromatase inhibitor.

The present work encompasses a combined experimental and theoretical investigation of the molecular structure, vibrational wavenumbers, electronic structure at the ground and electronic excited states, molecular electrostatic potential surface of 7-(Trifluoromethyl)-1H-indole-2-carboxylic acid (TICA) and possibility of the title molecule as an aromatase inhibitor using molecular docking and molecular dynamic simulations. A stable conformer has been obtained using potential energy scans by varying appropriate dihedral angles. The obtained minimum energy conformer was further optimized at the 6-311++G (d, p) basis set by applying the most accepted B3LYP functional. A good agreement between experimental and calculated normal modes of vibration has been observed. The hydrogen-bonded interaction between two monomeric units of TICA has been investigated using NBO,QTAIM, and NCI (noncovalent interactions) analysis. Molecular docking of TICA with human placental aromatase (PDB ID: 3S79) reveals the formation of polar hydrogen bonds as well as hydrophobic interactions between the ligand and the protein, right in the binding cavity. TICA satisfies all pharmacokinetic filters (Lipinski rule of five, the Veber rule, Ghose rule, Egan rule, as well as the Muegge rule) and has a high bioavailability score of 0.85. Dynamic stability of the ligand within the binding pocket of the target protein has been confirmed by 100 ns molecular dynamics simulation results. The present study provides an excellent starting point for additional in vivo research, and TICA may eventually serve as a significant therapeutic candidate for the treatment of breast cancer.

Study on molecular structure, spectroscopic behavior, NBO, and NLO analysis of 3-methylbezothiazole-2-thione.

Experimentally observed spectral data (FT-TR and FT-Raman) of 3-methylbezothiazole-2-thione (3MBT2T) were compared with the spectral data obtained by DFT/B3LYP method using 6-311++G(d,p) basis set. UV-Vis spectrum of the title compound was recorded and the electronic properties, such as frontier molecular orbitals and band gap energies were calculated by TD-DFT approach. The molecular properties like dipole moment, polarizability, first static hyperpolarizability, molecular electrostatic potential surface (MEPs), and contour map were calculated to get a better comprehension of the properties of the title molecule. Natural bond orbital (NBO) analysis was applied to investigate the stability of the molecule arising from charge delocalization. Global and local reactivity descriptors were also computed to predict reactivity and reactive sites on the molecule.

Spectroscopic (FT-IR, FT-Raman, and UV-visible) and quantum chemical studies on molecular geometry, Frontier molecular orbitals, NBO, NLO and thermodynamic properties of 1-acetylindole.

Quantum chemical calculations of ground state energy, geometrical structure and vibrational wavenumbers of 1-acetylindole were carried out using density functional (DFT/B3LYP) method with 6-311++G(d,p) basis set. The FT-IR and FT-Raman spectra were recorded in the condensed state. The fundamental vibrational wavenumbers were calculated and a good correlation between experimental and scaled calculated wavenumbers has been accomplished. Electric dipole moment, polarizability and first static hyperpolarizability values of 1-acetylindole have been calculated at the same level of theory and basis set. The results show that the 1-acetylindole molecule possesses nonlinear optical (NLO) behavior with non-zero values. Stability of the molecule arising from hyper-conjugative interactions and charge delocalization has been analyzed using natural bond orbital (NBO) analysis. UV-Visible spectrum of the molecule was recorded in the region 200-500nm and the electronic properties like HOMO and LUMO energies and composition were obtained using TD-DFT method. The calculated energies and oscillator strengths are in good correspondence with the experimental data. The thermodynamic properties of the compound under investigation were calculated at different temperatures.

FT-IR, FT-Raman, NMR, UV and quantum chemical studies on monomeric and dimeric conformations of 3,5-dimethyl-4-methoxybenzoic acid.

Extensive spectroscopic investigations along with theoretical quantum chemical studies on 3,5-dimethyl-4-methoxybenzoic acid (DMMBA) have been consummated. The fundamental vibrational transitions were addressed by experimental FT-IR (4000-400cm(-1)) and FT-Raman (4000-10cm(-1)) techniques and density functional calculations at B3LYP/6-311++G(d,p) and B3LYP/6-311++G(df,pd) levels of theory. The (1)H, (13)C and DEPT 135 NMR spectra of studied compound were recorded in deuterated dimethylsulfoxide (DMSO-d6), and compared with computed data obtained by using gauge including atomic orbital (GIAO) method. The electronic absorption spectra in methanol and ethanol solution were evaluated in the range of 200-400nm, and TD-DFT method was chosen for computational study. The spectroscopic and theoretical results were compared to the corresponding properties for monomer and dimer structures for the most stable conformer. Stability of the molecule arising from hyperconjugative interactions and charge delocalization has been analyzed using natural bond orbital (NBO) analysis. Moreover, the thermodynamic and nonlinear optical (NLO) properties were evaluated.