title: Structure-activity relationships in cytotoxic Au(I)/Au(III) complexes derived from 2-(2'-pyridyl)benzimidazole.
abstract: 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 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 [(μ-pbi)Au2Cl3] (7), [(Ph3P)Au(μ-pbi)AuX2]PF6 (X = Cl ((8(+))(PF6(-))), AcO ((9(+))(PF6(-)))), and the binuclear Au(I)-Au(I) compound [(μ-pbi)Au2(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) × 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.
authors.affiliation: Dipartimento di Scienze Chimiche e Geologiche, Università degli Studi di Cagliari , S.S. 554 bivio per Sestu, 09042 Monserrato (Cagliari), Italy.
authors.forename: Laura
authors.initials: L
authors.lastname: Maiore
authors.forename: Maria Carla
authors.initials: MC
authors.lastname: Aragoni
authors.forename: Carlo
authors.initials: C
authors.lastname: Deiana
authors.forename: Maria Agostina
authors.initials: MA
authors.lastname: Cinellu
authors.forename: Francesco
authors.initials: F
authors.lastname: Isaia
authors.forename: Vito
authors.initials: V
authors.lastname: Lippolis
authors.forename: Anna
authors.initials: A
authors.lastname: Pintus
authors.forename: Maria
authors.initials: M
authors.lastname: Serratrice
authors.forename: Massimiliano
authors.initials: M
authors.lastname: Arca
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D001562:Benzimidazoles / Q000737:chemistry*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004354:Drug Screening Assays, Antitumor; D006046:Gold / Q000737:chemistry*; D006801:Humans; D015394:Molecular Structure; D050607:Organogold Compounds / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D011789:Quantum Theory; D013329:Structure-Activity Relationship
chemical_list: C479869:2-(2'-pyridyl)benzimidazole; D000970:Antineoplastic Agents; D001562:Benzimidazoles; D050607:Organogold Compounds; D006046:Gold