Molecular conformation, vibrational spectroscopic and NBO analysis of atenolol and atenolol-hydrochlorothiazide cocrystals.

Geometry optimization of atenolol (ATN) in the gas phase was carried out using B3LYP-D3BJ/6-31++G(d,p), CAM-B3LYP/6-31++G(d,p) and M06-2X/6-31++G(d,p) levels of DFT. The computed structural parameters were compared with the data obtained by single crystal X-ray diffraction experiment. Chemical reactivity (electronegativity, electrophilicity, hardness, chemical softness and chemical potential) was predicted with the help of HOMO- LUMO energy values. Experimental FT-IR was recorded and the calculated values were also analyzed using the same level of DFT. A complete vibrational spectrum was made to analyze the potential energy distribution (PED). Stability of the molecule arising from hyperconjugative interaction was analyzed by the natural bond orbital (NBO) analysis. The molecular electrostatic potential map was used to detect the possible electrophilic and nucleophilic sites in ATN molecule. Cocrystallization of atenolol-hydrochlorothiazide (ATN-HCTZ) was performed and the structure was analyzed by powder X-ray diffraction. NBO analysis was carried out on the ATN-HCTZ cocrystal for the elucidation of inter and intra-molecular hydrogen bonding interactions in the structure. Atenolol interaction with human serum albumin (HSA) was investigated by a molecular docking study.