Tumour-inhibiting platinum(ii) complexes with aminoalcoholligands: biologically important transformations studied by micellar electrokinetic chromatography, nuclear magnetic resonance spectroscopy and mass spectrometry

Abstract

(SP-4-2)-Bis[(R)-(−)-2-aminobutanol-κN]dichloroplatinum(II) and (SP-4-2)-bis[(R)-(−)-2-aminobutanolato-κ²N,O]platinum(II) are promising cytotoxic agents exhibiting a strongly pH-dependent rate of reaction with the DNA-modeling nucleotide guanosine 5′-monophosphate (GMP). This potential mode-of-action binding, directly correlating with cytotoxicity, is influenced by the intramolecular chelation of bifunctional aminoalcohol ligands which was examined by means of micellar electrokinetic chromatography (MEKC) and nuclear magnetic resonance (NMR). While NMR clearly proves the existence of equilibrium between the ring-opened and ring-closed species, no such transformation was observed under MEKC conditions. In a kinetic study performed by MEKC, the half-lives of GMP bound to the platinum complexes were determined and compared to the kinetic data acquired by capillary zone electrophoresis. An appreciable increase in binding in the presence of sodium dodecyl sulfate (SDS) micelles was explained in terms of activation of (SP-4-2)-bis[(R)-(−)-2-aminobutanol-κN]dichloroplatinum(II). This apparently takes place due to the shifting of the equilibrium towards the ring-opened species, induced by adduct formation between SDS and the platinum complex that was confirmed by electrospray ionization mass spectrometry.