Structural, spectroscopic (IR, Raman, and NMR), quantum chemical, and molecular docking analysis of (E)-2-(2,5-dimethoxybenzylidene)hydrazinecarbothioamide and its dimers

Abstract

Thiosemicarbazides are an important class of compounds with pronounced biological activities. In this contribution, the crystallographic structure of (E)-2-(2,5-dimethoxybenzylidene)hydrazinecarbothioamide (DBH) was described, and further spectroscopic studies (IR, Raman, 1H, and 13C NMR) studies were performed. Several density functional theory functionals (B3LYP, CAM-B3LYP, APFD, PBEPBE, M05-2X, and M06-2X) in conjunction with 6-311++G(d,p) were applied for the optimization of the structure. The highest resemblance to the crystallographic structure was obtained for structure optimized at M05-2X/6-311++G(d,p) level of theory. This structure was further used for the prediction of IR, Raman, and NMR spectra. The detailed vibrational and NMR analysis, with the most prominent bands assigned, proved that the experimental and theoretical spectra match well and that the obtained level of theory was suitable for the description of structure. Special emphasis was put on the analysis of dimers of DBH and water/DMSO-DBH structures to examine specific interactions. Natural Bond Orbital (NBO) and Quantum Atoms in Molecules (QTAIM) theories were applied for the quantification of the strength of these interactions. The most active positions were outlined through the calculation of the Fukui functions. A molecular docking study of DBH was performed towards Polo-like Kinase 1 (PLK1) to investigate the potential antitumor activity and the results were compared to volasertib. Specific interactions and binding affinities of monomers and dimers of DBH were discussed.