Copper(II) and dioxovanadium(V) complexes based on the antiproliferative chelating agent HDpk44mT: crystallographic analyses, spectroscopic features, and cytotoxicity

Single-crystal X-ray structures of hydrated di(2-pyridyl) ketone 4,4-dimethyl-3-thiosemicarbazone (HDpk44mT·H2O), the ternary ionic copper(II) complexes [Cu(Dpk-H-44mT)(phen)](ClO4)2·1(1/2)MeOH (1·1(1/2)MeOH) and [Cu(Dpk44mT)(phen)]ClO4 (2) (Dpk-H-44mT = zwitterionic) form of HDpk44mT; phen = 1,10-phenanthroline and the molecular dioxovanadium(V) complex [VO2(Dpk44mT)] (3) have been determined. Additionally, the solution structures of HDpk44mT·H2O and complex 3 have been elucidated with the aid of NMR spectroscopic techniques. Coordination compounds 1·1(1/2)MeOH, 2 and 3 represent extremely rare examples of thiosemicarbazone complexes of their specific kind possessing a di(2-pyridyl)-ketimine moiety. Under slightly acidic conditions, complex 1·1(1/2)MeOH is produced with the thiosemicarbazone ligand occurring in the zwitterionic thio-enolate form, but readily converts to complex 2 in basic medium. In the crystal lattice, these two copper(II) complexes show vastly different patterns of π-π stacking interactions. However, they have in common the ligand-imposed distorted square-pyramidal coordination geometry exhibiting a tetragonally induced disparity between the distances of the axial–equatorial CuII–Nphen bonds. X-band EPR spectroscopy demonstrated retention of the coordination sphere (gz > gx,y > 2.00; Az > Ax,y) in frozen solution. The crystallographic asymmetric unit of [VO2(Dpk44mT)] comprises two discrete molecules, one of which exhibits π-π stacking interactions. Their coordination geometry at the vanadium(V) center is severely distorted square pyramidal. Complexes 1·1(1/2)MeOH, 2 and 3 are electroactive with reduction potentials lying within the biologically accessible redox potential window. While the copper(II) complexes are highly efficacious as antiproliferative agents against the cancer cell lines HeLa and MCF-7, the main drawback is the lack of selectivity over the normal cell line MCF-10A. In sharp contrast, [VO2(Dpk44mT)] is specifically and selectively potent toward MCF-7 over HeLa and MCF-10A cells, and may provide impetus for further in vitro antitumor investigations.