Levina Aviva, Zhang Lianbo, Lay Peter A
Centre for Heavy Metal Research, School of Chemistry, University of Sydney, Sydney 2006 NSW, Australia.
Inorg Chem. 2003 Feb 10;42(3):767-84. doi: 10.1021/ic020621o.
Chromium(V) glutathione complexes are among the likely reactive intermediates in Cr(VI)-induced genotoxicity and carcinogenicity. The first definitive structure of one such complex, Cr(V)O(LH(2))(2)(-) (I; LH(5) = glutathione = GSH), isolated from the reaction of Cr(VI) with excess GSH at pH 7.0 (O'Brien, P.; Pratt, J.; Swanson, F. J.; Thornton, P.; Wang, G. Inorg. Chim. Acta 1990, 169, 265-269), has been determined by a combination of electrospray mass spectrometry (ESMS), X-ray absorption spectroscopy (XAS), EPR spectroscopy, and analytical techniques. In addition, Cr(V) complexes of GSH ethyl ester (gamma-Glu-Cys-GlyOEt) have been isolated and characterized by ESMS, and Cr(III) products of the Cr(VI) + GSH reaction have been isolated and characterized by ESMS and XAS. The thiolato and amido groups of the Cys residue in GSH are responsible for the Cr(V) binding in I. The Cr-ligand bond lengths, determined from multiple-scattering XAFS analysis, are as follows: 1.61 A for the oxo donor; 1.99 A for the amido donors; and 2.31 A for the thiolato donors. A significant electron withdrawal from the thiolato groups to Cr(V) in I was evident from the XANES spectra. Rapid decomposition of I in aqueous solutions (pH = 1-13) occurs predominantly by ligand oxidation with the formation of Cr(III) complexes of GSH and GSSG. Maximal half-lives of the Cr(V) species (40-50 s at [Cr] = 1.0 mM and 25 degrees C) are observed at pH 7.5-8.0. The experimental data are in conflict with a recent communication (Gaggelli, E.; Berti, F.; Gaggelli, N.; Maccotta, A.; Valensin, G. J. Am. Chem. Soc. 2001, 123, 8858-8859) on the formation of a Cr(V) dimer as a major product of the Cr(VI) + GSH reaction, which may have resulted from misinterpretation of the ESMS and NMR spectroscopic data.
铬（V）谷胱甘肽配合物可能是六价铬诱导遗传毒性和致癌性过程中的活性中间体。通过电喷雾质谱（ESMS）、X射线吸收光谱（XAS）、电子顺磁共振光谱（EPR）以及分析技术相结合的方法，已确定了从六价铬与过量谷胱甘肽在pH 7.0条件下反应中分离出的一种此类配合物Cr(V)O(LH(2))(2)(-)（I；LH(5)=谷胱甘肽=GSH）的首个确切结构。此外，谷胱甘肽乙酯（γ-Glu-Cys-GlyOEt）的铬（V）配合物已通过ESMS进行了分离和表征，六价铬与谷胱甘肽反应的铬（III）产物已通过ESMS和XAS进行了分离和表征。谷胱甘肽中半胱氨酸残基的硫醇基和酰胺基负责配合物I中铬（V）的结合。通过多重散射XAFS分析确定的铬-配体键长如下：氧供体为1.61 Å；酰胺供体为1.99 Å；硫醇供体为2.31 Å。从XANES光谱中可以明显看出，配合物I中硫醇基向铬（V）有显著的电子转移。配合物I在水溶液（pH = 1 - 13）中迅速分解，主要是通过配体氧化形成谷胱甘肽和氧化型谷胱甘肽的铬（III）配合物。在pH 7.5 - 8.0时观察到铬（V）物种的最大半衰期（在[Cr]=1.0 mM和25℃下为40 - 50 s）。实验数据与最近一篇关于形成铬（V）二聚体作为六价铬与谷胱甘肽反应主要产物的通讯文章（Gaggelli, E.; Berti, F.; Gaggelli, N.; Maccotta, A.; Valensin, G. J. Am. Chem. Soc. 2001, 123, 8858 - 8859）存在冲突，这可能是由于对ESMS和NMR光谱数据的错误解读导致的。
