Copper(II) and Dioxovanadium(V) Complexes Based on the Antiproliferative Chelating Agent HDpk44mT: Crystallographic...

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 Cu^II-N_phen bonds. X-band EPR spectroscopy demonstrated retention of the coordination sphere (g _z > g _x,y > 2.00; A _z > A _x,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.