Condensed-phase relative Gibbs free energy and E/Z descriptors for 2-acetylthiophene and 2-acetylthiophene-N1-phenyl thiosemicarbazones

Thiosemicarbazones (TSCs) encompasses a class of compounds relevant in the pharmacological context. Their specific applicability varies in function of the appropriated chemical modification and their binding to different transition metals. In the present work, we apply current standards functionals, B3LYP and B97D, with triple zeta basis set quality, 6-311++G(d,p), to investigate the relative stability of the various possible spatial arrangements for 2-acetylthiophene and 2-acetylthiophene-N1-phenyl thiosemicarbazones, denoted ATTSC and ATTSC-Ph, respectively. The relative stability of neutral and deprotonated species at ethanol described by an implicit solvent model was investigated. For ATTSC, the relative Gibbs energy changed significantly upon deprotonation, and for ATTSC-Ph, a novel global minimum was identified. Based on the present study, deprotonation determines population in condensed-media. Such information, valid for ATTSC and ATTSC-Ph, can be crucial in studying other thiosemicarbazones. Graphical abstract