Effects of the tetravanadate [V₄O₁₂]^4- anion on the structural, magnetic, and biological properties of copper/phenanthroline complexes

The aim to access linked tetravanadate [V4O12](4-) anion with mixed copper(II) complexes, using alpha-amino acids and phenanthroline-derived ligands, resulted in the formation of four copper(II) complexes [Cu(dmb)(Gly)(OH2)](2)[Cu(dmb)(Gly)](2)[V4O12]9H(2)O (1) [Cu(dmb)(Lys)](2)[V4O12]8H(2)O (2), [Cu(dmp)(2)][V4O12]C2H5OH11H(2)O (3), and [Cu(dmp)(Gly)Cl]2H(2)O (4), where dmb = 4,4 '-dimethioxy-2,2 '-bipyridine; Gly = glycine; Lys = lysine; and dmp = 2,9-dimethyl-1,10-phenanthroline. The [V4O12](4-) anion is functionalized with mixed copper(II) units in 1 and 2; while in 3, it acts as a counterion of two [Cu(dmp)](2+) units. Compound 4 crystallized as a unit that did not incorporate the vanadium cluster. All compounds present magnetic couplings arising from Cu & ctdot;O/Cu & ctdot;Cu bridges. Stability studies of water-soluble 3 and 4 by UV-Vis spectroscopy in cell culture medium confirmed the robustness of 3, while 4 appears to undergo ligand scrambling over time, resulting partially in the stable species [Cu(dmp)(2)](+) that was also identified by electrospray ionization mass spectrometry at m/z = 479. The in vitro cytotoxicity activity of 3 and 4 was determined in six cancer cell lines; the healthy cell line COS-7 was also included for comparative purposes. MCF-7 cells were more sensitive to compound 3 with an IC50 value of 12 +/- 1.2 nmol. The tested compounds did not show lipid peroxidation in the TBARS assay, ruling out a mechanism of action via reactive oxygen species formation. Both compounds inhibited cell migration at 5 mu M in wound-healing assays using MCF-7, PC-3, and SKLU-1 cell lines, opening a new window to study the anti-metastatic effect of mixed vanadium-copper(II) systems.