Journal
INORGANICA CHIMICA ACTA
Volume 359, Issue 1, Pages 44-52Publisher
ELSEVIER SCIENCE SA
DOI: 10.1016/j.ica.2005.08.030
Keywords
gold; gold(III); Au(Ill); anticancer; antitumor; polypyridyl; cytotoxicity; X-ray crystal structure and intercalate; solution chemistry; A2780; ovarian cancer
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This work reports the synthesis, characterization, and aqueous chemistry of a series of cytotoxic [Au(polypyridyl)Cl-2]PF6 complexes l(where polypyridyl = dipyrido[3,2-f.2',3'-h] quinoxaline (DPQ), dipyrido[3,2-a:2',3'-c] phenazine (DPPZ) and dipyrido[3,2-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 d(8) coordination complexes. The crystals of the complex belong to the space group P2(1)/n with a = 7.624(2) angstrom, b = 18.274(5) angstrom, c = 14.411(14) angstrom, beta = 98.03(3)degrees, and Z = 4. In 1 H 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 (A.2780) 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. (c) 2005 Elsevier B.V. All rights reserved.
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