engleski

Solid and Solution State Structural Characterization of Thiosemicarbazone Derivatives: A Combined Experimental and Theoretical Study

Thiosemicarbazones can exist in several tautomeric forms and conformations, with the possibility of intra- and intermolecular hydrogen bonding. Detailed structural characterization of thiosemicarbazones, as compounds that are associated with a wide spectrum of biological activities, is a prerequisite for better understanding of their bioactivity and for obtaining molecules with improved pharmacological properties. The aim of our research is to investigate the influence of substituents, the nature of the solvent (different polarity and different proton-donor and proton-acceptor abilities) and temperature on molecular conformation, tautomerism and nature of hydrogen bonding in salicylaldehyde and 2-methoxybenzaldehyde thiosemicarbazone derivatives. We present here a part of our study regarding the effect of substituting OH with OMe group in salycilaldehyde residue on the overall structure and thione-thiol tautomerism. Solid state structures of 1 (single polymorph) and 2 (two polymorphs) were characterized by single- crystal X-ray diffraction and high resolution 13C and 15N solid-state NMR spectroscopy. Since the crystal structure of 3 was reported previously, we employed 13C and 15N solid state NMR experiments which provided structural data complementary to those obtained by X-ray diffraction. Solid state NMR parameters were used as a reference for solution study results. Possible solvent induced conformational and tautomeric equilibrium changes were probed by multinuclear (1H, 13C and 15N) temperature dependent NMR experiments in CDCl3 and DMSO solutions. The experimental results were complemented with computational research of conformational space of selected compounds in a vacuum, and organic solvents (PCM approach), by combination of molecular- and quantum-mechanical methods. The most stable structures, obtained by molecular mechanics, were reoptimized in vacuum, CHCl3 and DMSO with B3LYP-D3/6-311++G(2df, 2p) computational model. QTAIM population analysis method was used for characterization of intramolecular hydrogen bonds in most stable conformers of investigated compounds.

thiosemicarbazones ; structure ; hydrogen bonding ; X-ray ; NMR spectroscopy ; conformational analysis

nije evidentirano