The trans labilization of cis-[PtCl2(13CH3NH2)2] by glutathione can be monitored at physiological pH by [1H,13C] HSQC NMR.
In order to monitor the trans labilization of cisplatin at physiological pH we have prepared the complex cis-[PtCl(2)((13)CH(3)NH(2))(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 (13)CH(3)NH(2) 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-NH(3) 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 (15)NH(3)-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.
Gibson
Dan
D
Department of Medicinal Chemistry and Natural Products, School of Pharmacy, The Hebrew University of Jerusalem, P.O. Box 12065, 91120 Jerusalem, Israel. gibson@md.huji.ac.il
Kasherman
Yonit
Y
Kowarski
Dina
D
Freikman
Inna
I
D002945:Cisplatin / Q000737:chemistry / Q000378:metabolism; D005978:Glutathione / Q000737:chemistry / Q000378:metabolism; D006863:Hydrogen-Ion Concentration; D009682:Magnetic Resonance Spectroscopy / Q000379:methods; D015394:Molecular Structure; D009944:Organoplatinum Compounds / Q000737:chemistry / Q000378:metabolism
D009944:Organoplatinum Compounds; D005978:Glutathione; D002945:Cisplatin