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谷胱甘肽对顺式-[PtCl2(13CH3NH2)2]的转位作用可在生理pH值下通过[1H,13C] HSQC NMR进行监测。

The trans labilization of cis-[PtCl2(13CH3NH2)2] by glutathione can be monitored at physiological pH by [1H,13C] HSQC NMR.

作者信息

Gibson Dan, Kasherman Yonit, Kowarski Dina, Freikman Inna

机构信息

Department of Medicinal Chemistry and Natural Products, School of Pharmacy, The Hebrew University of Jerusalem, P.O. Box 12065, 91120 Jerusalem, Israel.

出版信息

J Biol Inorg Chem. 2006 Mar;11(2):179-88. doi: 10.1007/s00775-005-0064-7. Epub 2005 Dec 10.

DOI:10.1007/s00775-005-0064-7
PMID:16341898
Abstract

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.

摘要

为了监测顺铂在生理pH值下的转位作用,我们制备了配合物顺式-[PtCl₂((¹³)CH₃NH₂)₂],并通过二维[¹H,¹³C]异核单量子相关(HSQC)核磁共振光谱研究了其在中性pH值的水溶液中与过量谷胱甘肽的相互作用。[¹H,¹³C] HSQC光谱是追踪(¹³)CH₃NH₂释放的好方法,但对于表征溶液中的铂物种并不理想。在顺铂与谷胱甘肽的反应中,形成了Pt-S键,Pt-NH₃键断裂。追踪顺铂Pt-S键形成的最佳技术是紫外光谱法。[¹H,¹³C] HSQC光谱是追踪Pt-N键断裂的最佳方法。[¹H,¹⁵N] HSQC光谱是表征溶液中不同物种的最佳方法。然而,在[¹H,¹⁵N] HSQC中,(¹⁵)NH₃-Pt-S区域峰的强度反映了Pt-S键形成(增加信号强度)和转位作用(降低信号强度)之间的平衡。[¹H,¹⁵N] HSQC光谱和[¹H,¹³C] HSQC光谱是互补技术,应结合使用以获得关于铂配合物与含硫配体相互作用的最准确信息。

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