Experimental and theoretical insights into structural features of methyl (E)-3-(3,4,5-trimethoxybenzylidene)dithiocarbazate with molecular docking and ADMET studies

A new Schiff base, methyl (E)-3-(3,4,5-trimethoxybenzylidene)dithiocarbazte (MTD), was successfully synthesized from a condensation reaction of methyldithiocarbazate with 3,4,5-trimethoxybenzaldehyde. The structure of MTD was confirmed by single-crystal X-ray, NMR, FTIR, TGA, UV-Vis and mass spectroscopy techniques. The Hirshfeld surface analysis of the MTD crystal structure showed dominant H⋅⋅⋅H contacts in the molecular system. Bond lengths and bond angles of the theoretical MTD structure optimized by density functional theory (DFT) using B3LYP label with 6-31G+(d,p) basis set showed excellent agreement with those of the crystal structure. The IR spectra calculated from ground-state vibrational frequency analysis and the UV-Vis spectra from time-dependent density functional theory correlate well with their respective experimental spectra. The results of frontier molecular orbitals (FMO), density of states and global descriptors such as chemical hardness, chemical potential, electrophilic index and chemical softness derived from FMOs with MTD optimized structure revealed that MTD is soft, polarizable, reactive and prone to intramolecular charge transfer. Close observation of frontier molecular orbital map indicated the N, S, O heteroatoms, phenyl ring and p‑methoxy group in negative potential regions while the rest of the molecule was in positive regions. Natural bond orbital analyses concluded that MTD is 98.085% Lewis structure. The molecular docking score result of MTD and Streptococcus pneumoniae protein (PDB code: 3OBH), which is very close to that of standard drugs (trimethoprim and sulfamethoxazole), suggests a potential drug candidature of MTD. The absorption, distribution, metabolism, excretion and toxicity (ADMET) study predicted the good drug-like character of MTD.