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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]

• Ex-Mal cocrystal formed by solution crystallization and confirmed by XRD and DSC. • Vibrational investigations highlighted the outcome of interacting groups. • O H (Mal) and C = O (Ex) groups formed intermolecular hydrogen bonding in cocrystal. • RDG analysis reveals the non-covalent bond interactions. • Reactivity descriptors, MEP, and drug-likeness endorse the pharmaceutical activity. The present study aimed to investigate the Exemestane - maleic acid (Ex-Mal) cocrystal using Fourier-transform Raman (FT-Raman), Fourier-transform Infrared (FT-IR), Powder X-ray Diffraction (PXRD) and Differential Scanning Calorimeter (DSC) experimental techniques and quantum chemical calculations. Exemestane (Ex) is an irreversible aromatase inhibitor, clinically used for the treatment of postmenopausal women having primary or advanced breast cancer. Maleic acid (Mal), a dicarboxylic acid is found in many vegetables and fruits and is used as a food additive and sweetener. Solution crystallization of Ex and Mal was done in the generation of Ex-Mal cocrystal (1:1). PXRD and DSC analysis confirmed the successful generation of Ex-Mal Cocrystal. Intermolecular hydrogen bonding (O4-H12···O13 & C8-O3···H36) also suggested the formation of a multi-component system, Ex-Mal cocrystal (1:1), as the respective modes shifted in the vibrational (Raman & IR) spectra of cocrystal than the Ex. Further, the quantum theory of atoms in molecules (QTAIM) has been done to analyze the strength and nature of inter-/intra molecular hydrogen bonding. Natural bond orbital (NBO) analysis was performed to check the stabilization energy of the system. The frontier molecular orbital (FMO) analysis predicted that Ex-Mal cocrystal is more reactive and less stable than Ex. Molecular electrostatic potential (MEP) surface showed that electrophilic (C16-H36)/(O4-H12), and nucleophilic (C8=O3) / (C17=O13) reactive groups in Ex/Mal and Mal/Ex, respectively, neutralized after the formation of Ex-Mal cocrystal, confirming the presence of hydrogen bonding interactions (C16-H36∙∙∙O3=C8) and (C17=O13∙∙∙H12-O4). Molar Refractivity (MR) was calculated to check the drug-likeness behaviours of Ex-mal cocrystal. This study provided a comparison of experimental and theoretical results to understand the hydrogen bonding interactions and structural activity of the system. [Display omitted] [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]

• 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]