Gold(I) and silver(I) complexes of 2,3-bis(diphenylphosphino)maleic acid: Structural studies and antitumour activity

• Published in: Inorganica Chimica Acta Vol. 358; no. 14; pp. 4237 - 4246
• Main Authors: Berners-Price, Susan J., Bowen, Richard J., Fernandes, Manuel A., Layh, Marcus, Lesueur, William J., Mahepal, Sherika, Mtotywa, Matolwandile M., Sue, Rodney E., van Rensburg, Constance E.J.
• Format: Journal Article
• Language: English
• Published: Elsevier B.V 15.11.2005
• Subjects: Antitumour agents; Gold complexes; Phosphine ligands; Silver complexes; Phosphine ligands; Antitumour agents; Gold complexes; Silver complexes
• ISSN: 0020-1693; 1873-3255
• DOI: 10.1016/j.ica.2005.03.056

The 2:1 and 1:2 adducts of Au(I) and 1:2 adducts of Ag(I) with the diphosphine 2,3-bis(diphenylphosphino)maleic acid (dpmaa) have been prepared in high yields. Crystal structures are described for the neutral digold complex (AuCl) 2(dpmaa) · 2thf ( 1) and the water-soluble bis-chelated complex [Au(dpmaa) 2]Cl · H 2O · CH 3OH ( 2). The cytotoxicity of 2 was studied in tests with eight different cell lines and no significant activity was found. The 2:1 and 1:2 adducts of Au(I) and 1:2 adducts of Ag(I) with the diphosphine 2,3-bis(diphenylphosphino)maleic acid (dpmaa) have been prepared in high yields. Crystal structures have been determined for the neutral digold complex (AuCl) 2(dpmaa) · 2thf ( 1) and the bis-chelated complex [Au(dpmaa) 2]Cl · H 2O · CH 3OH ( 2). For 1, conformational rigidity imposed by the ethylenic bridge facilitates the formation of short intramolecular Au–Au contacts with no evidence of similar intermolecular contacts. Complex 2 crystallizes with [Au(dpmaa) 2] + cations hydrogen bonded through the carboxyl groups to a water molecule and chloride anion to form a H-bonded chain along the a axis. 31P NMR titration of 1 with dpmaa in acetone shows conversion to 2 at Au:P–P ratios less than 1:1 indicating similar high thermodynamic and kinetic stabilities to other bis-chelated [Au(P–P) 2] + complexes containing 5- or 6-membered chelate rings. The ionic Au(I) complex 2 and the analogous Ag(I) complex [Ag(dpmma) 2]NO 3 ( 3) are highly water soluble. The in vitro cytotoxic activity of 2 was assessed against eight different cell lines and no significant activity was found. The solubility properties and solution behaviour of the complexes are compared to the analogous 1,2-bis(diphenylphosphino)ethane (dppe) complexes and the potential significance of these results to the antitumour properties of chelated 1:2 Au(I)diphosphine complexes are discussed.