Capillary zone electrophoresis and capillary zone electrophoresis-electrospray ionization mass spectrometry studies on the behavior of anticancer cis- and trans-[dihalidobis(2-propanone oxime)platinum(II)] complexes in aqueous solutions.
Anticancer chemotherapeutics with new modes of action are in great demand to overcome adverse effects, resistance problems and a limited application range. Among other approaches, trans-configured analogs of the established chemotherapy drug cisplatin show promising results in biological model systems. Herein we report on comparative studies on the stability of cis- and trans-[dihalidobis(2-propanone oxime)platinum(II)] (halido=Cl(-), Br(-), I(-)) complexes in phosphate buffer, using capillary zone electrophoresis (CZE) and CZE hyphenated to electrospray ionization-mass spectrometry (CZE-ESI-MS). The used conditions simulate those in the cytoplasm, being of importance for the activation of platinum anticancer agents for their reaction with DNA, the ultimate target. The configuration of the Pt center, i.e., cis or trans, accounts for the differing degradation kinetics of the compounds and in addition a significant influence of the halido leaving group was observed, with in case of the cis complexes pseudo first order rate constants of 0.268, 0.191 and 0.142h(-1) for Br(-), Cl(-), and I(-), respectively. Degradation of the trans isomers was significantly faster compared to their cis-configured counterparts also leading to different products which were characterized by hyphenation of CZE to ESI-MS.
University of Vienna, Institute of Inorganic Chemistry, Vienna, Austria.
Gerlinde
G
Grabmann
Samuel M
SM
Meier
Yulia Y
YY
Scaffidi-Domianello
Mathea S
MS
Galanski
Bernhard K
BK
Keppler
Christian G
CG
Hartinger
D000970:Antineoplastic Agents / Q000737:chemistry*; D019075:Electrophoresis, Capillary / Q000379:methods*; D007536:Isomerism; D010984:Platinum / Q000737:chemistry*; D021241:Spectrometry, Mass, Electrospray Ionization / Q000379:methods*
D000970:Antineoplastic Agents; D010984:Platinum