Glutathione is a biologically abundant and redox active tripeptide that serves to protect cells from oxidative stress and rid the body of toxic heavy metals. The present study examines the coordination complexes of glutathione (GSH) with redox active metals, Zn, Cu, and Fe, using infrared multiple photon dissociation (IRMPD) action spectroscopy with a free electron laser. For all three metals, a complex between the metal dication and deprotonated GSH was formed, M(GSH-H)+. The experimental IRMPD spectra were compared to scaled harmonic vibrational spectra calculated at the MP2(full)/6-311+G(d,p) level of theory after thorough exploration of conformational space using a simulated annealing protocol. Interestingly, spectra calculated at the B3LYP or ωB97XD level do not match experiment as well. These findings offer the first gas-phase spectroscopic evidence for how the biologically relevant metal ions coordinate with glutathione. There are spectral features that are common to all three metals, however, noting the differences in the strengths of the common features between the three metals enables an assessment of the preference or specificity that each individual metal has for a given coordination site. Additionally, all three redox active metals form structures where the deprotonated thiol of the cysteine side chain coordinates with the metal center, which is consistent with the involvement of the thiol site in biologically relevant redox chemistry.

中文翻译：

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通过 IRMPD 光谱和互补的 ab Initio 计算对 Zn2+、Cu2+ 和 Fe2+ 与谷胱甘肽络合物的结构测定


谷胱甘肽是一种生物丰富的氧化还原活性三肽，用于保护细胞免受氧化应激并清除体内有毒的重金属。本研究使用自由电子激光器的红外多光子解离 （IRMPD） 作用光谱检查了谷胱甘肽 （GSH） 与氧化还原活性金属 Zn、Cu 和 Fe 的配位复合物。对于所有三种金属，在金属介裂和去质子化 GSH 之间形成了络合物 M（GSH-H）+。在使用模拟退火协议对构象空间进行全面探索后，将实验 IRMPD 光谱与在 MP2（full）/6-311+G（d，p） 理论水平上计算的缩放谐波振动光谱进行了比较。有趣的是，在 B3LYP 或 ωB97XD 水平下计算的谱图也与实验不匹配。这些发现为生物学相关的金属离子如何与谷胱甘肽配位提供了第一个气相光谱证据。所有三种金属都有共同的光谱特征，但是，注意到三种金属之间共同特征强度的差异可以评估每种金属对给定配位点的偏好或特异性。此外，所有三种氧化还原活性金属都形成结构，其中半胱氨酸侧链的去质子化硫醇与金属中心协调，这与硫醇位点参与生物学相关的氧化还原化学一致。