Synthesis, characterization, and aqueous chemistry of cytotoxic Au(III) polypyridyl complexes

This work reports the synthesis, characterization, and aqueous chemistry of a series of cytotoxic Au(polypyridyl)Cl₂]PF₆ complexes {(where polypyridyl = dipyrido3,2-f:2′,3′-h] quinoxaline (DPQ), dipyrido3,2-a:2′,3′-c] phenazine (DPPZ) and dipyrido3,2-a:2′,3′-c](6,7,8,9-tetrahydro) phenazine (DPQC))}. The crystal structure of Au(DPQ)Cl₂]PF₆ was determined as example of the series and exhibits the anticipated square planar geometry common for d⁸ coordination complexes. The crystals of the complex belong to the space group P2₁/n with a = 7.624(2) Å, b = 18.274(5) Å, c = 14.411(14) Å, β = 98.03(3)°, and Z = 4. In ¹H NMR studies of these compounds in the presence of aqueous buffer, all four complexes rapidly converted to the dihydroxy species Au(polypyridyl)(OH)₂] in a stepwise fashion. However, the Au(polypyridyl)]³⁺ fragment believed to impart cytotoxicity in human ovarian cancer cell lines (A2780) remained intact and appeared stable for days. It was also noted that these Au(III) complexes were readily reduced in the presence of the common biological reducing agents, reduced glutathione and sodium ascorbate. How solution and redox stability may affect the biological activity of these novel Au(III) complexes is discussed.