Formation of carbonato and hydroxo complexes in the reaction of platinum anticancer drugs with carbonate.
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 [(1)H-(15)N] HSQC NMR and (15)N-labeled carboplatin, we observe that cis-[Pt(CBDCA-O)(OH)(NH(3))(2)](-), cis-[Pt(OH)(2)(NH(3))(2)], cis-[Pt(CO(3))(OH)(NH(3))(2)](-), and what may be cis-[Pt(CO(3))(NH(3))(2)] are produced when 1 is allowed to react in 23.8 mM carbonate buffer. When (15)N-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(CO(3))(OH)(NH(3))(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.
Di Pasqua
Anthony J
AJ
Department of Chemistry, Syracuse University, 111 College Place, CST, Rm 1-014, Syracuse, New York 13244-4100, USA.
Centerwall
Corey R
CR
Kerwood
Deborah J
DJ
Dabrowiak
James C
JC
D000970:Antineoplastic Agents / Q000737:chemistry*; D002254:Carbonates / Q000737:chemistry*; D006900:Hydroxylation; D008024:Ligands; D009682:Magnetic Resonance Spectroscopy; D015394:Molecular Structure; D017671:Platinum Compounds / Q000737:chemistry*
D000970:Antineoplastic Agents; D002254:Carbonates; D008024:Ligands; D017671:Platinum Compounds