Glutathione Complex Formation with Mercury(II) in Aqueous Solution at Physiological pH

Abstract

The mercury(II) complexes formed in neutral aqueous solution with glutathione (GSH, here denoted AH3 in its tri-protonated form) were studied using Hg LIII-edge extended X-ray absorption fine structure (EXAFS) and 199Hg NMR spectroscopy, complemented with electrospray ionization mass spectrometric (ESI-MS) analyses. The [Hg(AH)2]2− complex, with the Hg-S bond distances 2.325 ± 0.01 Å in linear S-Hg-S coordination and the 199Hg NMR chemical shift −984 ppm, dominates except at high excess of glutathione. In a series of solutions with CHg(II) ~17 mM and GSH/Hg(II) mole ratios rising from 2.4 to 11.8, the gradually increasing mean Hg-S bond distance corresponds to an increasing amount of the [Hg(AH)3]4− complex. ESI-MS peaks appear at −m/z values of 1208 and 1230 corresponding to the [Na4Hg(AH)2(A)]− and [Na5Hg(AH)(A)2]− species, respectively. In another series of solutions at pH = 7.0 with CHg(II) ~50 mM and GSH/Hg(II) ratios from 2.0 to 10.0, the Hg LIII-edge EXAFS and 199Hg NMR spectra show that at high excess of glutathione (~0.35 mol·dm−3) about ~ 70% of the total mercury(II) concentration is present as the [Hg(AH)3]4− complex, with the average Hg-S bond distance 2.42 ± 0.02 Å in trigonal HgS3 coordination. The proportions of HgSn species, n = 2, 3 and 4, quantified by fitting linear combinations of model EXAFS oscillations to the experimental EXAFS data in our present and previous studies, were used to obtain stability constants for the [Hg(AH)3]4− complex, and also for the [Hg(A)4]10− complex that is present at high pH. For Hg(II) in low concentration at physiological conditions (pH = 7.4, CGSH = 2.2 mM) the relative amounts in the HgS2 species [Hg(AH)2]2−, [Hg(AH)(A)]3− and the HgS3 complex [Hg(AH)3]4− was calculated to be 95 : 2 : 3. Our results are not consistent with the formation of dimeric Hg(II)-GSH complexes proposed in a recent EXAFS study.

Glutathione binding to dirhodium tetraacetate: a spectroscopic, mass spectral and computational study of an anti-tumour compound

“…Glutathione reacts with large, soft, metals such as the toxic metals Cd(II), Hg(II), Pb(II), and As(III) [18][19][20][21][22] . This tendency to bind soft metals also extends to the wide range of metals used in therapeutic complexes, for example, Ag(I), Bi(III), Pt(II) in cisplatin, and Au(I) in Auranofin 10,12,[23][24][25][26] .…”

Formulasi dan Uji Aktivitas Krim Pengkelat Merkuri Berbahan Dasar Ekstrak Etanol Alga Coklat (Sargassum sp.)

“…Kemampuan KP I dalam mengkelat merkuri dipelajari hanya dengan membandingkan kandungan merkuri yang ada dalam jaringan kulit tikus sebelum dan sesudah diberi KP I. Namun demikian, mengacu pada penelitian Mah and Jalilehvand (2010), interaksi yang terjadi antara logam merkuri dengan glutation adalah interaksi pengkelatan.…”

“…Struktur yang dimungkinkan untuk merkuri(II)-glutation pada pH 7 (Mah and Jalilehvand, 2010) Hasil analisis merkuri dengan AAS terhadap jaringan kulit tikus disajikan pada Tabel 5. Tabel 5 menunjukkan bahwa setelah pemberian krim bermerkuri, terdapat kadar merkuri pada jaringan kulit tikus, yaitu 10 hingga 15 kali tinggi dibandingkan dengan kontrol.…”

XAS examination of glutathione–cobalt complexes in solution

“…Despite an important interest in coordination chemistry of GSH, information about a full structural characterization of GSH complexes with transition metal cations is rather seldom. Studies dealing with the binding properties of GSH in solution have been focused on transition metal ions [12,[22][23][24][25][26][27][28] and especially on heavy metal ions [29][30][31][32][33]. To the best of our knowledge, only one x-ray structure of oxidized peptide, Cu(I)-GSSG complex, has been reported until now [34].…”