Tumor‐inhibiting platinum(II) complexes with aminoalcohol ligands: Comparison of the mode of action by capillary electrophoresis and electrospray ionization‐mass spectrometry

Abstract

Capillary electrophoresis (CE) was used as an assay for studying the interaction of (SP‐4‐2)‐bis[(R)‐(–)‐2‐aminobutanol)dichloroplatinum(II) (1) and (SP‐4‐2)bis(4‐aminobutanol)dichloroplatinum(II) (2) with guanosine 5'‐monophosphate (GMP). CE kinetic measurements carried out at two physiological pH levels indicated that upon increasing the pH, 1 showed an appreciable change in binding behavior, with the rate of binding increased for more than 10 times as expressed by apparent half‐life values of GMP (6.1 and 62.2 h at pH 6.0 and 7.4, respectively). The rate of GMP binding for 2 remained comparatively less affected by pH (half‐lives of 8.5 and 10.6 h, respectively). Regardless of the nature of platinum complex and pH, the reaction with GMP tends to be decelerated at increased chloride concentrations in solution, this effect being particularly pronounced when changing from 4 mM (intracellular level) to 100 mM (extracellular level). The kinetic differences of platinum complexes were characterized in terms of the respective GMP‐adducts structure, independently identified by means of off‐line electrospray ionization‐mass spectrometry. Also addressed was the interpretation of binding behavior as based on the structural features of the intact complexes, namely differing inclination to intramolecular chelation.