Crystal structure, Hirshfeld surface, DFT and BSA binding studies of dihydropyrazole-1-thiocarboxamides

Abstract

Two trifluoromethyl substituted pyrazole derivatives (PTC-1 and PTC-2) were synthesized, characterized using FT-IR, 1H NMR and X-ray studies, they were also explored for their interactions with plasma protein. Theoretically predicted structures of both the compounds using Density Functional Theory (DFT) were found to be in agreement with the experimentally obtained single crystals. Strong F-F interactions were observed in the case PTC-1 upon decomposition of Hirshfeld surface over dnorm in 2D-fingerprint region. Apart from this, strong H-bonding of F-H, S-H and O-H type was also observed in the case of both compounds which was supported by molecular electrostatic potential calculated using DFT method. The chemical reactivity and selectivity for both the compounds were assessed using DFT based global chemical descriptors. The low value of chemical hardness associated with PTC-1 and PTC-2 reflected their soft nature. Local descriptors in the form of condensed Fukui function were also calculated to explore the sites available for electrophilic and nucleophilic attack. Natural bond orbital (NBO) analysis reflected the hyper conjugative interactions present in both compounds. BSA binding studies were performed for both the compounds to explore their binding ability with the plasma protein which was further supported by docking studies.