TY - JOUR
T1 - Formation of carbonato and hydroxo complexes in the reaction of platinum anticancer drugs with carbonate
AU - Di Pasqua, Anthony J.
AU - Centerwall, Corey R.
AU - Kerwood, Deborah J.
AU - Dabrowiak, James C.
PY - 2009/2/2
Y1 - 2009/2/2
N2 - 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 [ 1H- 15N] HSQC NMR and 15N-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 15N-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.
AB - 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 [ 1H- 15N] HSQC NMR and 15N-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 15N-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.
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U2 - 10.1021/ic801579h
DO - 10.1021/ic801579h
M3 - Article
C2 - 19113934
AN - SCOPUS:60849130157
SN - 0020-1669
VL - 48
SP - 1192
EP - 1197
JO - Inorganic Chemistry
JF - Inorganic Chemistry
IS - 3
ER -