Formation of Carbonato and Hydroxo Complexes in the Reaction of Platinum Anticancer Drugs with Carbonate

摘要

The second-generation Pt-II anticancer drug carboplatin is here shown to react with carbonate, which is present in blood, interstitial fluid, cytosol, and culture medium, to produce platinum-carbonato and -hydroxo complexes. Using [H-1-N-15] HSQC NMR and N-15-labeled carboplatin, we observe that cis-[Pt(CBDCA-O)(OH)(NH3)(2)](-), cis-[Pt(OH)(2)(NH3)(2)], cis[Pt(CO3)(OH)(NH3)(2)](-), and what may be cis-[Pt(CO3)(NH3)(2)] are produced when 1 is allowed to react in 23.8 mM carbonate buffer. When N-15-labeled carboplatin is allowed to react in 0.5 M carbonate buffer, these platinum species, as well as other hydroxo and carbonato species, some of which may be dinuclear complexes, are produced. Furthermore, we show that the carbonato species cis-[Pt(CO3)(OH)(NH3)(2)](-) is also produced when cisplatin is allowed to react in carbonate buffer. The study outlines the conditions under which carboplatin and cisplatin form carbonato and aqua/hydroxo species in carbonate media.