Molecular Basis of the Antioxidant Capability of Glutathione Unraveled via Aerosol VUV Photoelectron Spectroscopy

Abstract

Glutathione (GSH), the most abundant nonenzymatic antioxidant in living systems, actively scavenges various exogenous/endogenous oxidizing species, defending important biomolecules against oxidative damages. Although it is well established that the antioxidant activity of GSH originates from the cysteinyl thiol (-SH) group, the molecular origin that makes the thiol group of GSH a stronger reducing agent than other thiol-containing proteins is unclear. To gain insights into the molecular basis underlying GSH's superior antioxidant capability, here we report, for the first time, the valence electronic structures of solvated GSH in the aqueous aerosol form via the aerosol vacuum ultraviolet photoelectron spectroscopy technique. The pH-dependent electronic evolution of GSH is obtained, and the possible correlations between GSH and its constituting amino acids are interrogated. The valence band maxima (VBMs) for GSH aqueous aerosols are found at 7.81, 7.61, 7.52, and 5.51 ± 0.10 eV at a pH of 1.00, 2.74, 7.00, and 12.00, respectively, which appear to be lower than the values of their corresponding hybrid counterparts collectively contributed from the three isolated constituting amino acids of GSH. An additional photoelectron feature is observed for GSH aqueous aerosols at pH = 12.00, where the thiol group on its Cys residue becomes deprotonated and the relatively well-separated feature allows its vertical ionization energy (VIE) to be determined as 6.70 ± 0.05 eV. Compared to a VIE of 6.97 ± 0.05 eV obtained for a similar thiolate feature observed previously for isolated Cys aqueous aerosols ( Su et al. VUV Photoelectron Spectroscopy of Cysteine Aqueous Aerosols: A Microscopic View of Its Nucleophilicity at Varying pH Conditions . J. Phys. Chem. Lett. 2015 , 6 , 817 - 823 ), a 0.27 eV reduction in the VIE is found for GSH, indicating that the outermost electron corresponding to the nonbonding electron on the thiolate group can be removed more readily from the GSH tripeptide than that from Cys alone. The possible origins underlying the decrease in the VBM of GSH with respect to that of each corresponding hybrid counterpart and the decrease in the VIE of the thiolate feature of GSH with respect to that of the isolated Cys are discussed, providing hints to understand the superior antioxidant capability of GSH from a molecular level.

Retracted: Activation of the Nrf2‐ARE Signaling Pathway Prevents Hyperphosphatemia‐Induced Vascular Calcification by Inducing Autophagy in Renal Vascular Smooth Muscle Cells

“…HO-1, one of the Nrf2 target genes, promotes autophagy and eliminates damaged mitochondria so as to repress oxidative stress in lipopolysaccharidetreated rat liver [Unuma et al, 2013;Zhang et al, 2016]. Among the Nrf2-targeting genes, g-GCS is an important regulator of synthesizing glutathione (GSH) which is the most rich small-molecule antioxidant that scavenges reactive oxygen species (ROS) as well as neutralizes electrophiles [Wild et al, 1999;Chang et al, 2016]. And an increase of g-GCS can enhance GSH synthesis, thereby improving the antioxidant capacity of the tissues and cells [Huang et al, 1993].…”

Guanidinium Group Remains Protonated in a Strongly Basic Arginine Solution

“… with the liquid jet method. The slight difference can be attributed to some uncertainties in the pH value measurement, and to temperature effects because the aqueous nanoparticles are thought to be super‐cooled after evaporation . To confirm the effectiveness of the nanoparticle method in probing the electronic structures of solvated species, we also measured partial electron‐yield near edge X‐ray absorption fine structure (NEXAFS) spectra (experimental details are given in the Supporting Information) of aqueous glycine nanoparticles generated from acidic and basic solutions (Figure S2) and compare them with those measured in Ref.…”

“…According to the calculation in Ref. , nanoparticles are expected to exist in a super‐cooled state at the photoionization point. When the temperature decreases, the equilibrium concentration of hydrogen ions (H + ) in a basic solution decreases because the self‐ionization of water and generation of H + is an endothermic process.…”

From atoms to aerosols: probing clusters and nanoparticles with synchrotron based mass spectrometry and X-ray spectroscopy

“…This was inspired by experiments performed by Chia Wang in Taiwan, who used aerosol based VUV photoelectron spectroscopy to follow proton transfer as pH was varied on biological aerosols. 131,132 We had employed VUV photoelectron imaging spectroscopy in 2005 to probe glycine and phenylalanine-glycine-glycine nanoparticles 30 and recently arginine using soft X-rays, 133 which will be discussed later in the article. To understand the pH dependent shifts in the valence photoelectron spectra (Fig.…”