Antitumour Metallocenes: Effect of DMSO on the Stability of Cp(2)TiX(2) and Implications for Anticancer Activity

The rate of hydrolysis of the aromatic rings of Cp(2)TiX(2) [X = CI 1, O(2)CCCl(3)8 and O(2)CCH(2)NH(3)Cl 13], in aqueous solutions, 10%DMSO and 100% DMSO have been studied by (1)H NMR spectroscopy. Rapid hydrolysis of both the carboxylate and cyclopentadienyl ligands in Cp(2)TiX(2)[X = O(2)CCCl(3),O(2)CCH(2)NH(3)Cl] occurs in DMSO to give biologically inactive species. The rate of these reactions are concentration dependent as dilution of these samples with saline or water to give the therapeutic conditions of 10%DMSO/90%H(2)O slows the hydrolysis chemistry. In contrast, samples of Cp(2)TiX(2) [X = CI 1, O(2)CCH(2)NH(3)Cl13 ], dissolved in water give solutions containing the presumed antitumour active species in which the halide or glycine ligands have been hydrolysed but the Cp rings remain metal bound.