Chemical behavior and in vitro activity of mixed phosphine gold(I) compounds on melanoma cell lines

P-31 nuclear magnetic resonance and electrospray ionization-mass spectrometry studies on the melanoma cytotoxic chlorotriphenylphosphine-1,3-bis(diphenylphosphino)propanegold(I), [Au(DPPP)(PPh3)Cl], show partial decomposition that includes the novel dinuclear cation [Au-2(DPPP)(2)Cl](+); its structure was calculated by using the density functional theory (DFT). Unexpectedly, by using the. diphosphine ligand 1,2-bis(diphenylphosphino)ethane (DIPHOS), [{AuCl(PPh3)}(2)(mu(2)-DIPHOS)] was obtained. Its X-ray crystal structure shows a unique triangular coordination sphere in contrast to the T-shaped geometry of related Au(I)-DIPHOS compounds. Its cytotoxic activity in JR8, SK-Mel-5, and 2/60 melanoma cell lines is dose-dependent and lower than that of [Au(DPPP)(PPh3)Cl] because of its nonchelating nature. An in vitro study of the effect of both Au compounds on the B 16V melanoma cell line gives credence to this structure-activity relationship. IC50 indicates that both Au species are 10 times more active in B16V than in JR8, SK-Mel-5, and 2/60. Oxidation of [Au(DPPP)(PPh3)Cl] toward Au(III) compounds and phosphine-oxides is observed upon reaction with hypochlorite in water/dimethyl sulfoxide solution, mimicking endogenous hypochlorite. A related reaction involving the formation of [AUCl(4)](-) is thermodynamically feasible according to DFT calculations.