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The present work focuses on the structural properties, spectroscopic signatures, intermolecular hydrogen bonding interactions, chemical and biological activity of nicotinamide (NIC) based on its monomeric and trimeric models using density functional theory and vibrational spectroscopy. FT-IR and FT-Raman spectra were obtained using the double-side forward-backward acquisition mode under vacuum. UV-Vis absorption spectra were recorded in methanol and compared with the calculated values. Geometry optimization and vibrational wavenumbers were obtained with the aid of Gaussian 09 program packages. The structural analysis of NIC revealed that the trimeric model was in better agreement with the experimental values than the monomer due to the incorporation of nearest hydrogen bond interactions. Spectroscopic results showed that NH2 and C = O groups of NIC were involved in intermolecular interactions in the trimeric model. The natural bond orbital (NBO) and quantum theory of atoms in molecules (QTAIM) analyses determined the presence, strength as well as nature of the hydrogen bonds were partially covalent. The lesser value of the HOMO-LUMO energy gap for the trimeric model indicated higher reactivity than monomer. Moreover, chemical reactivity was calculated using molecular electrostatic potential surface (MESP) and reactivity descriptors. The docking studies for NIC with several targets explored its biological activity. [ABSTRACT FROM AUTHOR]

Abstract Molecular structure, chemical and physical reactivity, spectroscopic behavior, intermolecular interactions play an important role in understanding the biological nature of pharmaceutical drugs. The objective of the study is to combine the spectroscopic and computational methodology for the investigation of structural behavior of ezetimibe (EZT). Computational study was done on monomeric, dimeric and trimeric models of EZT using B3LYP/6-311G(d,p). Hydrogen bond interactions were taken into consideration to validate the theoretical results with the experimental one. Results obtained for trimeric model were better than monomer and dimer. HOMO-LUMO energy band gap shows that the chemical reactivity calculated using dimeric and trimeric model is higher than that of monomeric model. Higher value of electrophilicity index (ω = 2.5654 eV) also confirms that trimer behaves as a strong electrophile in comparison with monomer and dimer. To examine the hyperconjugation interactions and the stability of the molecule, natural bond analysis (NBO) was done on dimer and trimer of EZT. Nature and the strength of hydrogen bonds were examined by quantum theory of atoms in molecules (QTAIM). Binding energy calculated from counterpoise method was −7.40 kcal/mol for dimer and −21.47 kcal/mol for trimer. Graphical Abstract Figure showing the intermolecular hydrogen bonding between neighboring molecules and comparison of theoretical and experimental spectra. Unlabelled Image Highlights • Intermolecular hydrogen bond interactions were considered for detailed study of ezetimibe (EZT). • FT-IR and FT-Raman spectra for monomer, dimer and trimer of EZT were compared with the theoretical result. • NBO and AIM analysis have been done for the understanding of charge transfer within the molecule and the nature of bond. • Chemical reactivity of EZT has been investigated by MEPS and global reactivity descriptors. • Inclusion of hydrogen bonding provides good and comparable results between experimental and theoretical data. [ABSTRACT FROM AUTHOR]

Febuxostat (FXT) is a urate-lowering drug and xanthine oxidase inhibitor which is used for the treatment of hyperuricemia and gout caused by increased levels of uric acid in the blood (hyperuricemia). The present study aims to provide deeper knowledge of the structural, vibrational spectroscopic and physiochemical properties of FXT based on monomeric and dimeric model with the aid of combination of experimental and computational methods. The conformational analysis of form Q has been done to predict the possible structure of unknown form A. Vibrational spectra of form A and Q has been compared to get an idea of hydrogen bonding interactions of form A. A computational study of FXT has been executed at different level (B3LYP, M06-2X, WB97XD) of theory and 6–31 G (d, p) basis set for dimeric model to elucidate the nature of intermolecular hydrogen bond. The red shift observed in the stretching modes of OH, C O groups and blue shift in stretching mode of C N group in experimental as well as in theoretical spectra explains the involvement of these groups in intermolecular hydrogen bonding. NBO analysis shows that change in electron density (ED) in the lone pair orbital to σ* antibonding orbital (LP1 (N39) → σ* (O3-H38)) with maximum value of E(2) energy confirms the presence of hydrogen bond (N39⋯H38-O3) leading to dimer formation. Study of topological parameters was executed for dimer using Bader's atoms in molecules (AIM) theory predicting the partially covalent nature of hydrogen bonds present in the molecule. The study of molecular electrostatic potential surface (MEPS) map ascertains that the C O, C N group are prone to electrophilic attack and OH group is active towards nucleophilic attack. The lower energy band gap and higher value of softness of dimeric model of FXT indicates its more reactivity, polarisability than monomeric model. The local reactivity descriptors predict the order of reactive sites towards electrophilic, nucleophilic and radical attack. An investigation made to determine the ligand protein interaction of FXT through docking with different molecular targets reveals the inhibitive as well as antibacterial nature of FXT. [ABSTRACT FROM AUTHOR]

• Geometry optimization and conformational study of ricobendazole were performed. • Vibrational frequency assignments along with PED calculation have been presented. • NBO, QTAIM, and HOMO-LUMO have been analyzed in detail. • Protein-ligand interaction by molecular docking was discussed. The structural, spectroscopic (FT-IR and FT-Raman), and physicochemical properties of ricobendazole (RBZ) has been presented with the help of combined experimental and computational approaches. A comparison between the observed and simulated spectra show good agreement with each other. The conformational analysis was performed around eight flexible bonds to predict the most stable conformers, by employing density functional theory (DFT) at B3LYP/6–311++ G (d,p) level. The chemical reactivity has been demonstrated in terms of frontier molecular orbitals (HOMO-LUMO) energy gap, molecular electrostatic potential (MEP) surface, and global reactivity. The local reactivity descriptors explored an idea about the donor/acceptor/free radical reactive sites present in the molecule. Natural bond orbital (NBO) analysis was performed to study the interactions between bonding and antibonding orbitals. The intramolecular hydrogen bonding interactions were demonstrated using QTAIM theory. Binding sites against three targets such as Poly [ADP-ribose] polymerase-1, MAP kinase p38 alpha, and Adenosine A2a receptor were identified by molecular docking analysis as RBZ is believed to inhibit against them. Image, graphical abstract [ABSTRACT FROM AUTHOR]

Abstract In the present study, a combined theoretical and experimental approach is used to study the structure and properties of 4-methoxydalbergione (MD). The optimized geometry was calculated by B3LYP method using 6–311++G(d,p) basis set. Three conformers of MD (MD I, MD II and MD III) have been found by potential energy surface scan. The FT-Raman and FT-IR spectra were recorded in the solid phase, and interpreted in terms of potential energy distribution analysis. Good consistency is found between the calculated results and observed spectra. The detailed interpretation of electron delocalization from filled lone pair orbitals to unfilled antibonding molecular orbitals of most interacting molecular orbitals of the molecule has been done by natural bond orbital (NBO) analysis. HOMO-LUMO energy gap shows that chemical reactivity of MD II is higher than MD I and MD III. Molecular electrostatic potential (MEP) surface has also been predicted with the help of density functional theory. Global and local reactivity descriptors are used to study the chemical reactivity of the molecule. Chemical reactivity parameters show that MD II is softer and chemically more reactive than MD I and MD III. Topological parameters at bond critical points (BCP) have been evaluated by 'Quantum theory of atoms in molecules' (QTAIM). The docking studies revealed that the active sites C=O of MD showed best binding energies of −5.17, −5.43, −4.31,-4.77, −5.86 and −4.77for 5O3L, 1HTM, 3UV5, 5I1Q, 1MU7 and 1QZQ respectively, which are bacterial proteins of Escherichia coli. Graphical abstract Image 1 Highlights 1. Molecular structure and vibrational analysis of 4-methoxydalbergione (MD) were presented using FT-IR and FT- Raman spectroscopy and quantum chemical calculations. 2. The UV–Visible absorption spectrum was examined in DMSO solvent and compared with one calculated in gas phase as well as in solvent environment. 3. HOMO-LUMO energy gap shows that chemical reactivity of MD. 4. Natural Bond Orbital (NBO) analysis is followed to figure out the stability of the molecule 5. Investigation of ligand-protein interaction, molecular docking simulations has also been done on bacterial proteins. [ABSTRACT FROM AUTHOR]

• Computational and experimental work has been performed on cocrystal of hydrochlorothiazide (HCTZ) and nicotinamide (NCT). • H-bonding interaction was studied by using monomeric, dimeric and trimeric models of HCTZ-NCT cocrystal. • NH 2 and C = O groups were involved in neighbouring hydrogen bonding interactions. • QTAIM and NBO analysis were done to explore inter and intramolecular H-bond interactions. • MEPS was performed to observe the reactive sites of the molecules. The present work focuses on the study of structural, vibrational, chemical properties and the effect of hydrogen bonding interaction in the formation of a cocrystal of hydrochlorothiazide (HCTZ, a diuretic drug) with nicotinamide (NCT) using vibrational spectroscopy (FT-IR and FT-Raman) and density functional theory. HCTZ being a BCS class IV drug, has low permeability and solubility; therefore, its cocrystal is studied. Monomer, dimer and trimer of HCTZ-NCT cocrystal were studied to understand hydrogen bonding interactions. The shifting in the wavenumber and the elongation in bond lengths of the amide (NH 2) group of HCTZ and carbonyl (C = O) group of NCT were observed in all the models of HCTZ-NCT cocrystal due to the hydrogen bonding interaction. The importance of hydrogen bonding were also explored by natural bond orbital (NBO) analysis in support of the quantum theory of atom in molecules (QTAIM). The chemical reactivity of HCTZ, NCT and HCTZ-NCT cocrystal was examined by MEPS map, FMOs, global electronic reactivity descriptor, ECT descriptors, and molar refractivity. The lesser value of the HOMO-LUMO energy gap in the cocrystal than API reflects that the chemical reactivity of the cocrystal was better than API itself. The comparison between API(HCTZ) and cocrystal (HCTZ-NCT) implies that pharmaceutical cocrystals may be a better option to improve and enhance the pharmacological properties of drugs. [Display omitted] [ABSTRACT FROM AUTHOR]

This study aims to investigate the structural and vibrational features of cefradine (the first-generation cephalosporin antibiotic) based on spectroscopic experiments and theoretical quantum chemical approach. The fundamental structural aspects of cefradine have been examined based on optimized geometry, spectroscopic behavior, intermolecular interaction, chemical reactivity, intramolecular hydrogen bonding, and molecular docking analysis. The most stable minimum energy conformer of the title molecule was identified by performing a one-dimensional potential energy surface scan along the rotational bonds at B3LYP/6-311++G (d,p) level of theory. The vibrational features of the molecule and information about the coupled modes were predicted. The chemical reactivity and stability of all the possible conformers of cefradine were estimated based on the HOMO-LUMO energy gap and NBO approach. The overall picture of accumulation of charges on individual atoms of the molecule was predicted by molecular electrostatic potential (MEP) surface map which in turn identifies the nucleophilic and electrophilic region or sites. The quantitative analysis of electrophilicity and nucleophilicity indices was done by Hirshfeld charge analysis and it was found that N8 atom is the most prominent site for nucleophilic attack while C14 atom is feasible for electrophilic attack. QTAIM study has also been performed to investigate the nature and strength of hydrogen bonding interactions. Besides, molecular docking studies were performed to examine the active binding residues of the target. Unlabelled Image • Geometry optimization and conformational studies of cefradine have been performed. • Experimental IR and Raman spectra are compared with the simulated spectra. • Local and global reactivity descriptors have been studied. • Docking analysis of cefradine with selected targets has been investigated. [ABSTRACT FROM AUTHOR]