TY - JOUR
T1 - The trans labilization of cis-[PtCl2(13CH 3NH2)2] by glutathione can be monitored at physiological pH by [1H,13C] HSQC NMR
AU - Gibson, Dan
AU - Kasherman, Yonit
AU - Kowarski, Dina
AU - Freikman, Inna
PY - 2006/3
Y1 - 2006/3
N2 - In order to monitor the trans labilization of cisplatin at physiological pH we have prepared the complex cis-[PtCl2(13CH 3NH2)2] and studied its interactions with excess glutathione in aqueous solution at neutral pH by two-dimensional [1H,13C] heteronuclear single-quantum correlation (HSQC) NMR spectroscopy. [1H,13C] HSQC spectroscopy is a good method for following the release of 13CH 3NH2 but is not so good for characterizing the Pt species in solution. In the reaction of cisplatin with glutathione, Pt-S bonds are formed and Pt-NH3 bonds are broken. The best technique for following the formation of Pt-S bonds of cisplatin is by UV spectroscopy. [1H,13C] HSQC spectroscopy is the best method for following the breaking of the Pt-N bonds. [1H,15N] HSQC spectroscopy is the best method for characterizing the different species in solution. However, the intensity of the peaks in the 15NH3-Pt-S region, in [1H,15N] HSQC, reflects a balance between the formation of Pt-S bonds, which increases the signal intensity, and the trans labilization, which decreases the signal intensity. [1H,15N] HSQC spectroscopy and [1H,13C] HSQC spectroscopy are complementary techniques that should be used in conjunction in order to obtain the most accurate information on the interaction of platinum complexes with sulfur-containing ligands.
AB - In order to monitor the trans labilization of cisplatin at physiological pH we have prepared the complex cis-[PtCl2(13CH 3NH2)2] and studied its interactions with excess glutathione in aqueous solution at neutral pH by two-dimensional [1H,13C] heteronuclear single-quantum correlation (HSQC) NMR spectroscopy. [1H,13C] HSQC spectroscopy is a good method for following the release of 13CH 3NH2 but is not so good for characterizing the Pt species in solution. In the reaction of cisplatin with glutathione, Pt-S bonds are formed and Pt-NH3 bonds are broken. The best technique for following the formation of Pt-S bonds of cisplatin is by UV spectroscopy. [1H,13C] HSQC spectroscopy is the best method for following the breaking of the Pt-N bonds. [1H,15N] HSQC spectroscopy is the best method for characterizing the different species in solution. However, the intensity of the peaks in the 15NH3-Pt-S region, in [1H,15N] HSQC, reflects a balance between the formation of Pt-S bonds, which increases the signal intensity, and the trans labilization, which decreases the signal intensity. [1H,15N] HSQC spectroscopy and [1H,13C] HSQC spectroscopy are complementary techniques that should be used in conjunction in order to obtain the most accurate information on the interaction of platinum complexes with sulfur-containing ligands.
KW - Cisplatin
KW - Glutathione
KW - [1H,13C] heteronuclear single-quantum correlation
KW - cis-[PtCl(CHNH )]
KW - trans labilization
UR - http://www.scopus.com/inward/record.url?scp=32444433747&partnerID=8YFLogxK
U2 - 10.1007/s00775-005-0064-7
DO - 10.1007/s00775-005-0064-7
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C2 - 16341898
AN - SCOPUS:32444433747
SN - 0949-8257
VL - 11
SP - 179
EP - 188
JO - Journal of Biological Inorganic Chemistry
JF - Journal of Biological Inorganic Chemistry
IS - 2
ER -