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Kinetics and mechanism for reduction of Pt(IV) anticancer model compounds by Se-methyl L-selenocysteine. Comparison with L-selenomethionine.

Liu, Chunli; Xu, Liyao; Tian, Hongwu; Yao, Haiping; Elding, Lars Ivar LU and Shi, Tiesheng (2018) In Journal of Molecular Liquids 2018(271). p.838-843
Abstract (Swedish)
Se-methyl L-selenocysteine (MeSeCys) is one of the major organic selenium compounds acquired from the diet by human beings. It has been shown to have anticancer activity and cancer prevention functions. However, its antioxidant activity, largely related to its biological function, has not been well characterized so far. We here report a stopped-flow kinetic study of the reduction of the Pt(IV) anticancer model compounds trans-[PtX2(CN)4]2− (X = Cl; Br) by MeSeCys in a wide pH range. Overall second-order kinetics is established for the redox reactions, and spectrophotometric titrations indicate a 1:1 reaction stoichiometry. The MeSeCys is oxidized to its selenoxide form, as identified by high-resolution mass spectra. The proposed reaction... (More)
Se-methyl L-selenocysteine (MeSeCys) is one of the major organic selenium compounds acquired from the diet by human beings. It has been shown to have anticancer activity and cancer prevention functions. However, its antioxidant activity, largely related to its biological function, has not been well characterized so far. We here report a stopped-flow kinetic study of the reduction of the Pt(IV) anticancer model compounds trans-[PtX2(CN)4]2− (X = Cl; Br) by MeSeCys in a wide pH range. Overall second-order kinetics is established for the redox reactions, and spectrophotometric titrations indicate a 1:1 reaction stoichiometry. The MeSeCys is oxidized to its selenoxide form, as identified by high-resolution mass spectra. The proposed reaction mechanism involves parallel attack on one of the trans-coordinated halides of the Pt(IV) complexes by the selenium atom of the various MeSeCys protolytic species. Rate constants for the rate determining steps as well as the pKa values of the various protolytic species of MeSeCys have been determined at 25.0 °C and 1.0 M ionic strength. A bridged two-electron transfer mechanism for the rate-determining steps is supported by rapid-scan spectra, activation parameters, and by the much larger reaction rate of [PtBr2(CN)4]2− compared to [PtCl2(CN)4]2−. The experiments indicate that the reduction of [PtX2(CN)4]2− by MeSeCys proceeds via a similar reaction mechanism as L-selenomethionine (SeMet) studied previously. However, there is a large reactivity difference between these two selenium compounds, as a matter of fact the largest one observed so far when compared to other redox systems. It differs between the various protolytic species of MeSeCys and SeMet. The different reactivity of MeSeCys and SeMet in the reduction of various biologically relevant oxidants might account for their disparate efficacies as anticancer agents. (Less)
Abstract
Se-methyl L-selenocysteine (MeSeCys) is one of the major organic selenium compounds acquired from the diet by human beings. It has been shown to have anticancer activity and cancer prevention functions. However, its antioxidant activity, largely related to its biological function, has not been well characterized so far. We here report a stopped-flow kinetic study of the reduction of the Pt(IV) anticancer model compounds trans-[PtX2(CN)4]2− (X = Cl; Br) by MeSeCys in a wide pH range. Overall second-order kinetics is established for the redox reactions, and spectrophotometric titrations indicate a 1:1 reaction stoichiometry. The MeSeCys is oxidized to its selenoxide form, as identified by high-resolution mass spectra. The proposed reaction... (More)
Se-methyl L-selenocysteine (MeSeCys) is one of the major organic selenium compounds acquired from the diet by human beings. It has been shown to have anticancer activity and cancer prevention functions. However, its antioxidant activity, largely related to its biological function, has not been well characterized so far. We here report a stopped-flow kinetic study of the reduction of the Pt(IV) anticancer model compounds trans-[PtX2(CN)4]2− (X = Cl; Br) by MeSeCys in a wide pH range. Overall second-order kinetics is established for the redox reactions, and spectrophotometric titrations indicate a 1:1 reaction stoichiometry. The MeSeCys is oxidized to its selenoxide form, as identified by high-resolution mass spectra. The proposed reaction mechanism involves parallel attack on one of the trans-coordinated halides of the Pt(IV) complexes by the selenium atom of the various MeSeCys protolytic species. Rate constants for the rate determining steps as well as the pKa values of the various protolytic species of MeSeCys have been determined at 25.0 °C and 1.0 M ionic strength. A bridged two-electron transfer mechanism for the rate-determining steps is supported by rapid-scan spectra, activation parameters, and by the much larger reaction rate of [PtBr2(CN)4]2− compared to [PtCl2(CN)4]2−. The experiments indicate that the reduction of [PtX2(CN)4]2− by MeSeCys proceeds via a similar reaction mechanism as L-selenomethionine (SeMet) studied previously. However, there is a large reactivity difference between these two selenium compounds, as a matter of fact the largest one observed so far when compared to other redox systems. It differs between the various protolytic species of MeSeCys and SeMet. The different reactivity of MeSeCys and SeMet in the reduction of various biologically relevant oxidants might account for their disparate efficacies as anticancer agents. (Less)
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Contribution to journal
publication status
published
subject
keywords
Platinum(IV), Anticancer, selenocysteine, selenomethionine, reduction, kinetics, reaction mechanism, Platinum(IV), selenocysteine, selenomethionine, Anticancer agents, reduction, reaction mechanism, kinetics, selenium
in
Journal of Molecular Liquids
volume
2018
issue
271
pages
6 pages
publisher
Elsevier
external identifiers
  • scopus:85053500278
ISSN
0167-7322
DOI
10.1016/j.molliq.2018.09.056
language
English
LU publication?
yes
id
960f904a-7ac4-4bf1-8732-de73947c55fb
date added to LUP
2018-09-21 12:54:57
date last changed
2019-01-06 14:05:24
@article{960f904a-7ac4-4bf1-8732-de73947c55fb,
  abstract     = {Se-methyl L-selenocysteine (MeSeCys) is one of the major organic selenium compounds acquired from the diet by human beings. It has been shown to have anticancer activity and cancer prevention functions. However, its antioxidant activity, largely related to its biological function, has not been well characterized so far. We here report a stopped-flow kinetic study of the reduction of the Pt(IV) anticancer model compounds trans-[PtX2(CN)4]2− (X = Cl; Br) by MeSeCys in a wide pH range. Overall second-order kinetics is established for the redox reactions, and spectrophotometric titrations indicate a 1:1 reaction stoichiometry. The MeSeCys is oxidized to its selenoxide form, as identified by high-resolution mass spectra. The proposed reaction mechanism involves parallel attack on one of the trans-coordinated halides of the Pt(IV) complexes by the selenium atom of the various MeSeCys protolytic species. Rate constants for the rate determining steps as well as the pKa values of the various protolytic species of MeSeCys have been determined at 25.0 °C and 1.0 M ionic strength. A bridged two-electron transfer mechanism for the rate-determining steps is supported by rapid-scan spectra, activation parameters, and by the much larger reaction rate of [PtBr2(CN)4]2− compared to [PtCl2(CN)4]2−. The experiments indicate that the reduction of [PtX2(CN)4]2− by MeSeCys proceeds via a similar reaction mechanism as L-selenomethionine (SeMet) studied previously. However, there is a large reactivity difference between these two selenium compounds, as a matter of fact the largest one observed so far when compared to other redox systems. It differs between the various protolytic species of MeSeCys and SeMet. The different reactivity of MeSeCys and SeMet in the reduction of various biologically relevant oxidants might account for their disparate efficacies as anticancer agents.},
  author       = {Liu, Chunli and Xu, Liyao and Tian, Hongwu and Yao, Haiping and Elding, Lars Ivar and Shi, Tiesheng},
  issn         = {0167-7322},
  keyword      = {Platinum(IV),Anticancer,selenocysteine,selenomethionine,reduction,kinetics,reaction mechanism,Platinum(IV),selenocysteine,selenomethionine,Anticancer agents,reduction,reaction mechanism,kinetics,selenium},
  language     = {eng},
  month        = {09},
  number       = {271},
  pages        = {838--843},
  publisher    = {Elsevier},
  series       = {Journal of Molecular Liquids},
  title        = {Kinetics and mechanism for reduction of Pt(IV) anticancer model compounds by Se-methyl L-selenocysteine. Comparison with L-selenomethionine.},
  url          = {http://dx.doi.org/10.1016/j.molliq.2018.09.056},
  volume       = {2018},
  year         = {2018},
}