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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

Lemma, Kelemu LU ; Elmroth, Sofi LU and Elding, Lars Ivar LU (2002) In Journal of the Chemical Society. Dalton Transactions p.1281-1286
Abstract
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... (More)
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. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
platinum(II) complexes, chemoprotective ligands, rescue agents
in
Journal of the Chemical Society. Dalton Transactions
issue
7
pages
6 pages
publisher
Royal Society of Chemistry
external identifiers
  • wos:000175112500010
  • scopus:0036010405
ISSN
1472-7773
DOI
10.1039/b110138m
language
English
LU publication?
yes
id
5ee4effe-c41e-4419-bc6f-af071fdd3171 (old id 339885)
alternative location
http://www.rsc.org/ej/DT/2002/b110138m.pdf
date added to LUP
2007-10-31 13:16:28
date last changed
2017-12-10 04:31:35
@article{5ee4effe-c41e-4419-bc6f-af071fdd3171,
  abstract     = {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 &lt; Hcysteamine &lt; GSH &lt; thiourea &lt; thiosulfate &lt; DDTC with rate constants k(2) of 0.156 &amp;PLUSMN; 0.001, 0.22 &amp;PLUSMN; 0.01, 0.237 &amp;PLUSMN; 0,003, 1.17 &amp;PLUSMN; 0.01, 5.57 &amp;PLUSMN; 0,04, and 8.0 &amp;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 &amp;UDelta;H* and &amp;UDelta;S* have been determined and the products of the reaction of 1 with the rescue agents have been characterised.},
  author       = {Lemma, Kelemu and Elmroth, Sofi and Elding, Lars Ivar},
  issn         = {1472-7773},
  keyword      = {platinum(II) complexes,chemoprotective ligands,rescue agents},
  language     = {eng},
  number       = {7},
  pages        = {1281--1286},
  publisher    = {Royal Society of Chemistry},
  series       = {Journal of the Chemical Society. Dalton Transactions},
  title        = {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},
  url          = {http://dx.doi.org/10.1039/b110138m},
  year         = {2002},
}