Ring-Opened Adducts of the Anticancer Drug Carboplatin with Sulfur Amino Acids.
Reactions of the anticancer drug carboplatin ("Paraplatin") with a variety of sulfur-containing amino acids have been investigated by (1)H and (15)N NMR spectroscopy and by HPLC. Thiols react very slowly and sulfur-bridged species containing four-membered Pt(2)S(2) rings are the predominant products. In contrast, reactions with thioether ligands are much more rapid, and kinetics for the initial stages of the reaction with L-methionine have been determined (k = 2.7 x 10(-)(3) M(-)(1) s(-)(1)). Surprisingly, very stable ring-opened species are formed such as cis-[Pt(CBDCA-O)(NH(3))(2)(L-HMet-S)] which has a half-life for Met-S,N ring-closure of 28 h at 310 K. A study of the formation of the analogous product for N-acetyl-L-methionine and its subsequent ring closure is reported. Reactions such as these may play a role in the biological activity of carboplatin.
Barnham
Kevin J.
KJ
Gordon House and Christopher Ingold Laboratory, Department of Chemistry, Birkbeck College, University of London, 29 Gordon Square, London WC1H 0PP, U.K., and Department of Chemistry, National University of Singapore, 10 Kent Ridge Crescent, Singapore 0511.
Djuran
Milos I.
MI
Murdoch
Piedad del Socorro
PS
Ranford
John D.
JD
Sadler
Peter J.
PJ