Pyridyl Thiosemicarbazone Complexes of Ni (II), Cu (II), and Zn (II): Structural Insights and Neuropharmacological Activity

ABSTRACT Thiosemicarbazone‐based metal complexes have attracted considerable attention due to their rich coordination chemistry and emerging biological relevance; however, systematic correlations between their structural features and neuropharmacological activities remain limited. In this work, three metal complexes, [Ni(HcpmTsc) 2 ] ( 1 ), [Cu(HcpmTsc)(Cl)] ( 2 ), and [Zn(HcpmTsc) 2 ] ( 3 ), derived from N ‐(2‐chlorophenyl)‐2‐(pyridyl methylene) thiosemicarbazone ( H 2 cpmTsc ), were synthesized and comprehensively characterized using spectral techniques. In addition, complexes 1 and 3 were characterized by single‐crystal X‐ray diffraction, whereas the crystal structure of complex 2 had been reported earlier; however, its sedative and anxiolytic activities have been evaluated for the first time in the present study. Structural analyses revealed distorted octahedral geometries for complexes 1 and 3, with the ligand acting as a uninegative tridentate donor in all cases. The crystal structures reveal extended supramolecular assemblies stabilized by intermolecular C‐H···N and C‐H···S interactions. Photoluminescence studies demonstrated that the ligand and all complexes exhibit fluorescent behavior. To address the paucity of neuropharmacological investigations on such systems, the synthesized compounds were evaluated for sedative and anxiolytic activities using established animal models. The results indicated notable sedative and anxiolytic effects mediated predominantly through GABA A receptor pathways, with [Ni(HcpmTsc) 2 ] ( 1 ) showing the highest activity. Molecular docking studies supported these findings by confirming favorable receptor interactions. Overall, this study highlights the therapeutic potential of these complexes as candidates for neuropharmacological development.