Antitumour metallocenes: Effect of DMSO on the stability of Cp 2TiX2 and implications for anticancer activity

Abstract

The rate of hydrolysis of the aromatic rings of Cp2TiX 2 [X = Cl 1, O2CCCl3 8 and O 2CCH2NH3Cl 13], in aqueous solutions, 10%DMSO and 100% DMSO have been studied by 1H NMR spectroscopy. Rapid hydrolysis of both the carboxylate and cyclopentadienyl ligands in Cp 2TiX2 [X = O2CCCl3, O 2CCH2NH3Cl] 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%H2O slows the hydrolysis chemistry. In contrast, samples of Cp2TiX2 [X = Cl 1, O 2CCH2NH3Cl 13], 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.