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Kinetics and Mechan...
Kinetics and Mechanism for Reduction of Oral Anticancer Platinum(IV) Dicarboxylate Compounds by L-Ascorbate Ions
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- Lemma, Kelemu (författare)
- Lund University,Lunds universitet,Kemiska institutionen,Institutioner vid LTH,Lunds Tekniska Högskola,Department of Chemistry,Departments at LTH,Faculty of Engineering, LTH,Addis Ababa University
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- Sargeson, Alan M. (författare)
- Australian National University
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- Elding, Lars Ivar (författare)
- Lund University,Lunds universitet,Centrum för analys och syntes,Kemiska institutionen,Institutioner vid LTH,Lunds Tekniska Högskola,Centre for Analysis and Synthesis,Department of Chemistry,Departments at LTH,Faculty of Engineering, LTH
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(creator_code:org_t)
- Royal Society of Chemistry (RSC), 2000
- 2000
- Engelska 7 s.
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Ingår i: Journal of the Chemical Society, Dalton Transactions. - : Royal Society of Chemistry (RSC). - 1472-7773 .- 1470-479X .- 1364-5447. ; 2000:7, s. 1167-1172
- Relaterad länk:
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http://dx.doi.org/10...
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https://lup.lub.lu.s...
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Abstract
Ämnesord
Stäng
- Ascorbate (Asc) reductions of the oral anticancer platinum(IV) prodrugs cis,trans,cis-[PtCl2(OAc)2(cha)(NH3)] (JM216) and cis,trans,cis-[PtCl2(OCOC3H7)2(cha)(NH3)] (JM221) and of the isomers of JM216, viz.trans,cis,cis-[PtCl2(OAc)2(cha)(NH3)] (JM394) and trans,trans,trans-[PtCl2(OAc)2(cha)(NH3)] (JM576) (OAc = acetate, cha = cyclohexylamine) have been investigated in a 1.0 M aqueous perchlorate medium using stopped-flow and conventional UV/VIS spectrophotometry as a function of temperature and pH. JM216 and 221 are reduced to cis-[PtCl2(cha)(NH3)] (JM118) and JM394 and 576 to cis- and trans-[Pt(OAc)2(cha)(NH3)], respectively. The redox reactions follow the second-order rate law: −d[Pt(IV)]/dt = k [Pt(IV)] [Asc]tot where k is a pH dependent second-order overall rate constant and [Asc]tot = [Asc2−] + [HAsc−] + [H2Asc]. Reduction of JM216 and JM221 is slow (overall rate constants k298 = 5.08 ± 10−2 and 3.25 × 10−2 mol−1 dm3 s−1 at pH 7.12, respectively) and is suggested to take place via an outer-sphere mechanism. Reductions of JM394 and JM576 are more than three orders of magnitude faster (k298 = 230 ± 6 mol−1 dm3 s−1 at pH 7.0 for JM394). They are suggested to take place by a mechanism involving a reductive attack on one of the mutually trans chloride ligands by Asc2− and less efficiently by HAsc− leading to the formation of a chloride-bridged activated complex. The second-order rate constants for reduction of JM394 by HAsc− and Asc2− at 25 °C are 0.548 ± 0.004 and (4.46 ± 0.01) × 106 mol−1 dm3 s−1, respectively. The rate constants for reduction of JM216 and JM221 by Asc2− at 25 °C are calculated to be 672 ± 15 and 428 ± 10 mol−1 dm3 s−1, respectively and reduction by HAsc− was not observed under these conditions. Thus, Asc2− is up to 7 orders of magnitude more efficient as a reductant than HAsc−. H2Asc is virtually inactive. The activation parameters ΔH ‡ and ΔS‡ for reduction of JM216, JM221, JM394, and JM576 by Asc2− are 52 ± 1, 46 ± 1, 56.2 ± 0.5, and 63 ± 2 kJ mol−1 and −97 ± 4, −120 ± 4, −24 ± 2, and −8 ± 5 J K−1 mol−1, respectively. An isokinetic relationship gives further support to the mechanistic assignments.
Ämnesord
- NATURVETENSKAP -- Kemi -- Oorganisk kemi (hsv//swe)
- NATURAL SCIENCES -- Chemical Sciences -- Inorganic Chemistry (hsv//eng)
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Läkemedelskemi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Medicinal Chemistry (hsv//eng)
Nyckelord
- Platinum(IV)
- Ascorbate
- Reduction
- Pro-drug
- Anti-cancer drug
- Reaction mechanism
Publikations- och innehållstyp
- art (ämneskategori)
- ref (ämneskategori)
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