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: Laura Maiore, Maria Carla Aragoni, Carlo Deiana, Maria Agostina Cinellu, Francesco Isaia, Vito Lippolis, Anna Pintus, Maria Serratrice, Massimiliano Arca
• Journal: Inorganic chemistry (Inorg Chem) Vol. 53 Issue 8 Pg. 4068-80 (Apr 21 2014) ISSN: 1520-510X [Electronic] United States
• PMID: 24679072 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• 2-(2'-pyridyl)benzimidazole
• Antineoplastic Agents
• Benzimidazoles
• Organogold Compounds
• Gold

Topics

• Antineoplastic Agents (chemical synthesis, chemistry, pharmacology)
• Benzimidazoles (chemistry)
• Cell Line, Tumor
• Cell Proliferation (drug effects)
• Dose-Response Relationship, Drug
• Drug Screening Assays, Antitumor
• Gold (chemistry)
• Humans
• Molecular Structure
• Organogold Compounds (chemical synthesis, chemistry, pharmacology)
• Quantum Theory
• Structure-Activity Relationship