Structure-Activity Relationships in Cytotoxic AuI/AuIII Complexes Derived from 2-(2′-Pyridyl)benzimidazole

Gold(I) and gold(III) complexes derived from 2-(2'-pyridyI)benzimidazole (pbiH) were proven to be a promising class of in vitro antitumor agents against A2780 human ovarian cancer cells. In this paper, a comparative electrochemical, UV-vis absorption, and emission spectroscopic investigation is reported on pbiH, the two mononuclear Au-III complexes [(pbi)AuX2] (X = Cl (1), AcO (2)), the four mononuclear Au-I derivatives [(pbiH)AuCl] (3), [(pbiH)Au(PPh3)]PF6 ((4(+))(PF6-)), [(pbi)Au(PPh3)] (5), and [(pbi)Au(TPA)] (6), the three mixed-valence Au-III/Au-I complexes [(mu-pbi)Au2Cl3] (7), [(Ph3P)Au(mu-pbi)AuX2] PF6 (X = Cl ((8(+))(PF6-)), AcO ((9(+))(PF6-))), and the binuclear Au-I-Au-I compound [(mu-pbi)Au-2(PPh3)(2))PF6 ((10(+))(PF6-)). All complexes feature irreversible reduction processes related to the Au-III/Au-I or Au-I/Au-0 processes and peculiar luminescent emission at about 360-370 nm in CH2Cl2, with quantum yields that are remarkably lower ((0.7-14.5) X 10(-2)) in comparison to that determined for the free pbiH ligand (31.5 X 10(-2)) in the same solvent. The spectroscopic and electrochemical properties of all complexes were interpreted on the grounds of time-dependent PBEO/DFT calculations carried out both in the gas phase and in CH2Cl2 implicitly considered within the IEF-PCM SCRF approach. The electronic structure of the complexes, and in particular the energy and composition of the Kohn-Sham LUMOs, can be related to the antiproliferative properties against the A2780 ovarian carcinoma cell line, providing sound quantitative structure activity relationships and shedding a light on the role played by the global charge and nature of ancillary ligands in the effectiveness of Au-based antitumor drugs.