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
(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)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/339885
- author
- Lemma, Kelemu LU ; Elmroth, Sofi LU and Elding, Lars Ivar LU
- organization
- publishing date
- 2002
- 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
- 2016-04-01 16:13:54
- date last changed
- 2022-02-27 19:47:24
@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 < 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.}},
author = {{Lemma, Kelemu and Elmroth, Sofi and Elding, Lars Ivar}},
issn = {{1472-7773}},
keywords = {{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}},
doi = {{10.1039/b110138m}},
year = {{2002}},
}