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Substitution reactions of [Pt(dien)Cl](+), [Pt(dien)(GSMe)](2+), cis-[PtCl2(NH3)(2)] and cis-[Pt(NH3)(2)(GSMe)(2)](2+) (GSMe = S-methylglutathione) with some sulfur-bonding chemoprotective agents

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Summary, in English

Sulfur-containing compounds are used as rescue agents to protect normal tissue from the toxic side effects of cis-[PtCl2(NH3)(2)] (cisplatin) without affecting its anti-tumour activity. Reactions of the model complexes [Pt(dien)Cl](+) (1) and [Pt(dien)(GSMe)](2+) (2) (GSMe = S-methylglutathione) with the rescue agents glutathione (GSH), thiourea, thiosulfate, and diethyldithiocarbamate (DDTC) have been studied in a 1.0 mol dm(-3) aqueous perchlorate medium at 37degreesC and pH 7.30 using stopped-flow and conventional UV/VIS spectrophotometry. The reactions of 1 with 2-mercaptoethanesulfonate (mesna) and 2-mercaptoethylamine (cysteamine), which is the parent compound of 2-(3-aminopropylamino)ethylphosphorothioic acid (WR2721), and of cis-[Pt(NH3)(2)(GSMe)(2)](2+) with thiosulfate have also been studied. The reactions between cisplatin and DDTC, thiourea and thiosulfate were investigated in an unbuffered 0.10-0.05 mol dm(-3) chloride medium at 37degreesC. All reactions follow the rate law: -d[complex]/dt = k(2)[Pt(II)][Nu] where k2 denotes a second-order rate constant and [Nu] is the total concentration of nucleophile. The rate law indicates that the reactions proceed via a direct nucleophilic substitution pathway. The rescue agents display a relatively narrow range of reactivity towards 1, mesna < Hcysteamine < GSH < thiourea < thiosulfate < DDTC with rate constants k(2) of 0.156 &PLUSMN; 0.001, 0.22 &PLUSMN; 0.01, 0.237 &PLUSMN; 0,003, 1.17 &PLUSMN; 0.01, 5.57 &PLUSMN; 0,04, and 8.0 &PLUSMN; 0.1 mol(-1) dm(1) s(-1), respectively. The sequence is consistent with the report that DDTC is the most effective rescue agent discovered so far when administered after cisplatin. The activation parameters &UDelta;H* and &UDelta;S* have been determined and the products of the reaction of 1 with the rescue agents have been characterised.

Publishing year

2002

Language

English

Pages

1281-1286

Publication/Series

Journal of the Chemical Society. Dalton Transactions

Issue

7

Document type

Journal article

Publisher

Royal Society of Chemistry

Topic

  • Inorganic Chemistry

Keywords

  • platinum(II) complexes
  • chemoprotective ligands
  • rescue agents

Status

Published

ISBN/ISSN/Other

  • ISSN: 1472-7773