Species-Specific Standard Redox Potential of Thiol-Disulfide Systems: A Key Parameter to Develop Agents against Oxidative Stress.

Arash Mirzahosseini,Béla Noszál

doi:10.1038/srep37596

Arash Mirzahosseini, Béla Noszál

Open Access

https://doi.org/10.1038/srep37596

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Abstract

Microscopic standard redox potential, a new physico-chemical parameter was introduced and determined to quantify thiol-disulfide equilibria of biological significance. The highly composite, codependent acid-base and redox equilibria of thiols could so far be converted into pH-dependent, apparent redox potentials (E’°) only. Since the formation of stable metal-thiolate complexes precludes the direct thiol-disulfide redox potential measurements by usual electrochemical techniques, an indirect method had to be elaborated. In this work, the species-specific, pH-independent standard redox potentials of glutathione were determined primarily by comparing it to 1-methylnicotinamide, the simplest NAD+ analogue. Secondarily, the species-specific standard redox potentials of the two-electron redox transitions of cysteamine, cysteine, homocysteine, penicillamine, and ovothiol were determined using their microscopic redox equilibrium constants with glutathione. The 30 different, microscopic standard redox potential values show close correlation with the respective thiolate basicities and provide sound means for the development of potent agents against oxidative stress.

Highlights

The general scheme of thiol-disulfide redox equilibria is generally studied at the level of phenomena; the three conditional equilibrium constants are in equations (1)–(3): K1C
In order to get a clear insight into the redox equilibria, purified from the protonation effects, an improved evaluation method was introduced to determine the species-specific redox equilibrium constants (k1, k2, k3)[14]
This work is the first attempt to comprehensively characterize thiol-disulfide redox equilibria in terms of the true ‘standard’ redox potentials, which are pH-independent

Summary

Introduction

The redox potentials of GSH and other thiols can only be determined indirectly by measurement of equilibrium constants for their reaction with redox systems of known redox potentials[7]. The general scheme of thiol-disulfide redox equilibria (as depicted in Fig. 1C) is generally studied at the level of phenomena; the three conditional equilibrium constants are in equations (1)–(3) (the symbols in square brackets mean total concentration, which are the sum of the concentration of all microspecies of the compound in question): K1C

Results

Conclusion