Complexes of Cytotoxic Chelators from the Dipyridyl Ketone Isonicotinoyl Hydrazone (HPKIH) Analogues

In an effort to better understand the antiproliferative effects of the tridentate hydrazone chelators di-2-pyridyl ketone
isonicotinoyl hydrazone (HPKIH) and di-2-pyridyl ketone benzoyl hydrazone (HPKBH), we report the coordination
chemistry of these ligands with the divalent metal ions, Mn, Co, Ni, Cu, and Zn. These complexes are compared
with their FeII analogues which were reported previously. The crystal structures of Co(PKIH)2, Ni(PKIH)2, Cu(PKIH)2, Mn(PKBH)2, Ni(PKBH)2, Cu(PKBH)2, and Zn(PKBH)2 are reported where similar bis-tridenate coordination
modes of the ligands are defined. In pure DMF, all complexes except the ZnII compounds exhibit metal-centered
MIII/II (Mn, Fe, Co, Ni) or MII/I (Cu) redox processes. All complexes show ligand-centered reductions at low potential.
Electrochemistry in a mixed water/DMF solvent only elicited metal-centered responses from the Co and Fe complexes.
Remarkably, all complexes show antiproliferative activity against the SK-N-MC neuroepithelioma cell line similar to
(HPKIH) or significantly greater than that of the (HPKBH) ligand which suggests a mechanism that does not only
involve the redox activity of these complexes. In fact, we suggest that the complexes act as lipophilic transport
shuttles that allow entrance to the cell and enable the delivery of both the ligand and metal which act in concert
to inhibit proliferation.