The preparation, characterisation and in vitro cytotoxicity of potentially chemotherapeutic heterobimetallic complexes containing early and late transition metals

Abstract

The reactions of phosphine Ph 2P(CH 2) 2SO 3Na with Cp 2M′Cl 2 (M′=Ti, Zr) in aqueous solution give the metallophosphines, Cp 2Ti(OSO 2(CH 2) 2PPh 2) 2 (Cp=cyclopentadienyl) and CpZr(OH)(OSO 2(CH 2) 2PPh 2) 2. These react with CODM″Cl 2 (M″=Pd, Pt) (COD=1,5-cyclooctadiene) in dichloromethane to give heterobimetallic complexes Cp 2Ti(OSO 2(CH 2) 2PPh 2) 2M″Cl 2 and CpZr(OH)(OSO 2(CH 2) 2 PPh 2) 2M″Cl 2 respectively. The compounds are characterised by infrared and NMR spectroscopies and elemental analysis. Electrospray mass spectra of the complexes are reported and compared to those of Cp 2M′Cl 2 in water and dimethylsulfoxide (DMSO). For zirconocene dichloride and its product heterobimetallic complexes, the addition of ethylenediamine tetraacetic acid disodium salt (Na 2H 2EDTA) was found to be an effective ionisation enhancement agent for the electrospray mass spectral studies. Cytotoxicity studies for the previously reported Cl 2Pt(PPh 2(CH 2) 2SO 3H) 2·3.5H 2O (Wedgwood et al., Inorg. Chim. Acta 290 (1999) 189), and the compounds Cp 2Ti(OSO 2(CH 2) 2 PPh 2) 2·1.5H 2O and Cp 2Ti(OSO 2(CH 2) 2PPh 2) 2PtCl 2·4H 2O reported here, have been evaluated by colony formation assay against cisplatin-sensitive and -resistant cell lines L929 and L929/R to highlight potential chemotherapeutic activity. The compound Cl 2Pt(PPh 2(CH 2) 2SO 3H) 2·3.5H 2O overcomes cisplatin resistance.