Synthesis, spectroscopic (IR and NMR), HOMO-LUMO, NLO, molecular docking and ADME study of (E)-2-(2-((5-chloro-3-methyl-1-phenyl-1H-pyrazol-4-yl)methylene)hydrazineyl)-4-(4-nitrophenyl)thiazole

Abstract

The three component reaction between 5‑chloro-3-methyl-1-phenyl-1H-pyrazole-4- carbaldehyde, thiosemicarbazide and 4-nitrophenacyl bromide furnished (E)-2-(2-((5‑chloro-3-methyl-1-phenyl-1H-pyrazol-4-yl)methylene)hydrazineyl)-4-(4 nitrophenyl)thiazole which was characterized by FT-IR and NMR spectral methods. These spectroscopic methods confirmed the structural framework of the titled compound. The density functional theory (DFT) approach with a 6–311++G(d,p) method was used and electronic and spectroscopic parameters were analyzed. Frontier molecular orbital analysis of the titled compound found a 3.13 eV energy gap with HOMO primarily populated on pyrazole and thiazole rings whereas LUMO populated on benzene carrying nitro group. According to the Non-Linear Optical (NLO) study, the titled compound might be significant in the fabrication of nonlinear optical materials. The results of the in-silico molecular docking study against cytochrome P450 14-sterol demethylase (CYP51) showed that hydrogen bonds, aromatic and hydrophobic interactions, and van Der Waals forces all contributed to strong binding affinity with the ligand. The experimental and computational spectral comparison led assignments of IR and NMR signals. The ADME predictions suggested a good pharmacological profile of the titled compound.