The preparation, characterisation and in vitro cytotoxicity of potentially chemotherapeutic heterobimetallic complexes containing early and late transition metals.
The reactions of phosphine Ph(2)P(CH(2))(2)SO(3)Na with Cp(2)M'Cl(2) (M'=Ti, Zr) in aqueous solution give the metallophosphines, Cp(2)Ti(OSO(2)(CH(2))(2)PPh(2))(2) (Cp=cyclopentadienyl) and CpZr(OH)(OSO(2)(CH(2))(2)PPh(2))(2). These react with CODM"Cl(2) (M"=Pd, Pt) (COD=1,5-cyclooctadiene) in dichloromethane to give heterobimetallic complexes Cp(2)Ti(OSO(2)(CH(2))(2)PPh(2))(2)M"Cl(2) and CpZr(OH)(OSO(2)(CH(2))(2) PPh(2))(2)M"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(2)M'Cl(2) in water and dimethylsulfoxide (DMSO). For zirconocene dichloride and its product heterobimetallic complexes, the addition of ethylenediamine tetraacetic acid disodium salt (Na(2)H(2)EDTA) was found to be an effective ionisation enhancement agent for the electrospray mass spectral studies. Cytotoxicity studies for the previously reported Cl(2)Pt(PPh(2)(CH(2))(2)SO(3)H)(2).3.5H(2)O (Wedgwood et al., Inorg. Chim. Acta 290 (1999) 189), and the compounds Cp(2)Ti(OSO(2)(CH(2))(2) PPh(2))(2).1.5H(2)O and Cp(2)Ti(OSO(2)(CH(2))(2)PPh(2))(2)PtCl(2).4H(2)O 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(2)Pt(PPh(2)(CH(2))(2)SO(3)H)(2).3.5H(2)O overcomes cisplatin resistance.
Wedgwood
Janet L
JL
Department of Chemical Engineering, University of Birmingham, Edgbaston B15 2TT, UK.
Kresinski
Roman A
RA
Merry
Stephen
S
Platt
Andrew W G
AW
D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry* / Q000494:pharmacology*; D002945:Cisplatin / Q000494:pharmacology; D019008:Drug Resistance, Neoplasm; D004354:Drug Screening Assays, Antitumor; D004492:Edetic Acid / Q000737:chemistry; D009682:Magnetic Resonance Spectroscopy; D008670:Metals / Q000737:chemistry* / Q000494:pharmacology*; D051379:Mice; D009942:Organometallic Compounds / Q000737:chemistry / Q000494:pharmacology; D010720:Phosphines / Q000737:chemistry; D021241:Spectrometry, Mass, Electrospray Ionization / Q000379:methods; D013329:Structure-Activity Relationship; D028561:Transition Elements / Q000737:chemistry* / Q000494:pharmacology*; D014407:Tumor Cells, Cultured
D000970:Antineoplastic Agents; D008670:Metals; D009942:Organometallic Compounds; D010720:Phosphines; D028561:Transition Elements; D004492:Edetic Acid; C044646:phosphine; D002945:Cisplatin