31P 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 [Au2(DPPP)2Cl]+; 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(?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 B16V 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 [AuCl4]- is thermodynamically feasible according to DFT calculations
Chemical Behavior and in Vitro Activity of Mixed Phosphine Gold(I) Compounds on Melanoma Cell Lines.
2008
Abstract
31P 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 [Au2(DPPP)2Cl]+; 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(?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 B16V 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 [AuCl4]- is thermodynamically feasible according to DFT calculationsI documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
