Seleno-Auranofin (Et3PAuSe-tagl): Synthesis, Spectroscopic (EXAFS, 197Au Mssbauer, 31P, 1H, 13C, and 77Se NMR, ESI-MS) Characterizatio

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• 作者：David T. Hill ; Anvarhusein A. Isab ; Don E. Griswold ; Michael J. DiMartino ; Elizabeth D. Matz ; Angel L. Figueroa ; Joyce E. Wawro ; Charles DeBrosse ; William M. Reiff ; Richard C. Elder ; Benjamin Jones ; J
• 刊名：Inorganic Chemistry
• 出版年：2010
• 出版时间：September 6, 2010
• 年：2010
• 卷：49
• 期：17
• 页码：7663-7675
• 全文大小：1006K
• 年卷期：v.49,no.17(September 6, 2010)
• ISSN：1520-510X

文摘

Seleno-auranofin (SeAF), an analogue of auranofin (AF), the orally active antiarthritic gold drug in clinical use, was synthesized and has been characterized by an array of physical techniques and biological assays. The Mssbauer and extended X-ray absorption fine structure (EXAFS) parameters of the solid compound demonstrate a linear P−Au−Se coordination environment at a gold(I) center, analogous to the structure of auranofin. The p>31p>P, p>13p>C, and p>1p>H NMR spectra of SeAF in chloroform solution closely resemble those of auranofin. The p>77p>Se spectrum consists of a singlet at 481 ppm, consistent with a metal-bound selenolate ligand. The absence of p>2p>J_PSe coupling in the p>31p>P and p>77p>Se spectra may arise from dynamic processes occurring in solution or because the p>2p>J_PSe coupling constants are smaller than the observed bandwidths. Electrospray ionization mass spectrometry (ESI-MS) spectra of SeAF in 50:50 methanol−water exhibited strong signals for [(Et₃P)₂Au]p>+p>, [(Et₃PAu)₂-μ-Se-tagl]p>+p>, and [Au(Se-tagl)₂]p>−p>, which arise from ligand scrambling reactions. Three assays of the anti-inflammatory activity of SeAF allowed comparison to AF. SeAF exhibited comparable activity in the topically administered murine arachadonic acid-induced and phorbol ester-induced anti-inflammatory assays but was inactive in the orally administered carragenan-induced assay in rats. However, in vivo serum gold levels were comparable in the rat, suggesting that differences between the in vivo metabolism of the two compounds, leading to differences in transport to the inflamed site, may account for the differential activity in the carrageenan-induced assay. Reactions of serum albumin, the principal transport protein of gold in the serum, demonstrated formation of AlbSAuPEt₃ at cysteine 34 and provided evidence for facile reduction of disulfide bonds at cysteine 34 and very rapid formation of Et₃P═O, a known metabolite of auranofin.