Impact of Hydrogen Bonding on the Susceptibility of Peptides to Oxidation

• Published in: Chemistry, an Asian journal Vol. 12; no. 13; pp. 1485 - 1489
• Main Authors: Chan, Bun, Moran, Damian, Easton, Christopher J., Radom, Leo
• Format: Journal Article
• Language: English
• Published: Germany Wiley Subscription Services, Inc 04.07.2017
• Subjects: amino acids; Biological activity; Bonding; Chemical bonds; Chemistry; Complexation; Hydrogen; Hydrogen Bonding; Ionization; ionization energies; Oxidation; Oxidation-Reduction; Peptides; Peptides - chemistry; theoretical calculations; oxidation; hydrogen bonding; peptides; theoretical calculations; ionization energies; amino acids
• ISSN: 1861-4728; 1861-471X
• DOI: 10.1002/asia.201700492

The tendency of peptides to be oxidized is intimately connected with their function and even their ability to exist in an oxidative environment. Here we report high‐level theoretical studies that show that hydrogen bonding can alter the susceptibility of peptides to oxidation, with complexation to a hydrogen‐bond acceptor facilitating oxidation, and vice versa, impacting the feasibility of a diverse range of biological processes. It can even provide an energetically viable mechanistic alternative to direct hydrogen‐atom ion. We find that hydrogen bonding to representative reactive groups leads to a broad (≈400 kJ mol−1) spectrum of ionization energies in the case of model amide, thiol and phenol systems. While some of the oxidative processes at the extreme ends of the spectrum are energetically prohibitive, subtle environmental and solvent effects could potentially mitigate the situation, leading to a balance between hydrogen bonding and oxidative susceptibility. Ionization energy spectrum: Increased hydrogen bonding, through to full deprotonation, results in a spectrum of ionization energies for key functional groups, leading to subtle mechanisms and environmental factors that are likely to provide a fine balance between hydrogen bonding and oxidation, which impacts on a broad range of oxidative processes involving peptides.