Synthesis, Structure, and Biologic Activity of Some Copper, Nickel, Cobalt, and Zinc Complexes with 2-Formylpyridine N4-Allylthiosemicarbazone

A series of zinc(II) ([Zn(H2O)(L)Cl] (1)), copper (II) ([Cu(L)Cl] (2), [Cu(L)Br] (3), [Cu-2(L)(2)(CH3COO)(2)]center dot 4H(2)O (4)), nickel(II) ([Ni(HL)(2)]Cl-2 center dot H2O (5)), and cobalt(III) ([Co(L)(2)]Cl (6)) complexes were obtained with 2-formylpyridine N-4-allylthiosemicarbazone (HL). In addition another two thiosemicarbazones (3-formylpyridine N-4-allylthiosemicarbazone (HLa) and 4-formylpyridine N-4-allylthiosemicarbazone (HLb)) have been obtained. The synthesized thiosemicarbazones have been studied using H-1 and C-13 NMR spectroscopy, IR spectroscopy, and X-ray diffraction analysis. The composition and structure of complexes were studied using elemental analysis, IR and UV-Vis spectroscopies, molar conductivity, and magnetic susceptibility measurements. Single crystal X-ray diffraction analysis elucidated the structure of thiosemicarbazones HL, HLa, and HLb, as well as complexes 4 and 5. The antiproliferative properties of these compounds toward a series of cancer cell lines (HL-60, HeLa, BxPC-3, RD) and a normal cell line (MDCK) have been investigated. The nickel complex shows high selectivity (SI > 1000) toward HL-60 cell line and is the least toxic. The zinc complex shows the highest selectivity toward RD cell line (SI = 640). The copper complexes (2-4) are the most active molecular inhibitors of proliferation of cancer cells, but exhibit not such a high selectivity and are significantly more toxic. Zinc and copper complexes manifest high antibacterial activity. It was found that calculated at B3LYP level of theory different reactivity descriptors of studied compounds strongly correlate with their biological activity.

Automated summary

A series of metal complexes were synthesized and characterized in this study. The synthesized compounds showed different inhibitory effects and selectivity on the proliferation of cancer cells and normal cells, with zinc and copper complexes exhibiting high antibacterial activity. Additionally, the study found that the biological activity of the compounds could be predicted using theoretical calculations.