Imidazole-based phosphane gold(I) complexes as potential agents for cancer treatment: Synthesis, structural studies and antitumour activity

Abstract

The reaction of the imidazolyl-4(5)-phosphane ligands 2-isopropylimidazol-4(5)yl-diphenylphosphane (4-MIP^iPr) and tris(2-isopropylimidazol-4(5)yl)phosphane (4-TIP^iPr) towards gold(I) has been explored and compared to those of analogous 1-methylimidazol-2-ylphosphane ligands. The structure of [(4-MIP^iPr)AuCl] (4) shows a linear P–Au–Cl coordination, whereas the 4-TIP^iPr ligand forms a dinuclear complex [{(4-TIP^iPr)Au}₂]Cl₂ (5). Here, 4-TIP^iPr bridges two gold(I) atoms in a head-to-tail P,N fashion. Complex 5 forms in the presence of the hard Lewis acid ZnCl₂ the bimetallic complex [AuCl(4-TIP^iPr)ZnCl]Cl (6), in which 4-TIP^iPr bridges the two metal centers. In accordance with the HSAB concept the Au(I) atom is coordinated by the P atom and the zinc(II) by three N atoms in a N,N,N fashion. The solid-state structures of the complexes 4–6 have been elucidated by single-crystal X-ray analysis. The Au(I)–Au(I) contact in 5 is 2.8821(15) Å. The biological activities of all imidazol-2-yl- and imidazol-4(5)-ylphosphane gold(I) complexes towards nine human cancer cell lines including seven ovarian cancer cell lines of different sensitivity towards cisplatin and two leukemia cell lines have been explored.