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

Gold(I) and gold(III) complexes derived from 2-(2′-pyridyl)-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 AuIII complexes [(pbi)AuX2] (X = Cl (1), AcO (2)), the four mononuclear AuI derivatives [(pbiH)AuCl] (3), [(pbiH)Au-(PPh3)]PF6 ((4+)(PF6−)), [(pbi)Au(PPh3)] (5), and (pbi)Au(TPA)] (6), the three mixed-valence AuIII/AuI complexes [(μ-pbi)Au2Cl3] (7), [(Ph3P)Au(μ-pbi)AuX2]PF6(X = Cl ((8+)(PF6−)), AcO ((9+)(PF6−))), and the binuclear AuI−AuI compound [(μ-pbi)Au2(PPh3)2]PF6 ((10+)(PF6 −)). All complexes feature irreversible reduction processes related to the AuIII/AuI or AuI/Au0 processes and peculiar luminescent emission at about 360−370 nm in CH2Cl2, with quantum yields that are remarkably lower ((0.7−14.5) × 10−2) in comparison to that determined for the free pbiH ligand (31.5 × 10−2) in the same solvent. The spectroscopic and electrochemical properties of all complexes were interpreted on the grounds of time-dependent PBE0/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.