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

Abstract

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 · H2O · CH3OH (2). For 1, conformational rigidity imposed by the ethylenic bridge facilitates the formation of short intramolecular AuAu 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:PP ratios less than 1:1 indicating similar high thermodynamic and kinetic stabilities to other bis-chelated [Au(PP)2]+ complexes containing 5- or 6-membered chelate rings. The ionic Au(I) complex 2 and the analogous Ag(I) complex [Ag(dpmma)2]NO3 (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.