Oxidative Addition of Singlet Oxygen to Model Building Blocks of the Aerucyclamide A Peptide: A First-Principles Approach.

Singlet oxygen (1O2) is a significant source of biodamage in living organisms. 1O2 is a highly reactive excited electronic-state spin-configuration of molecular oxygen and is usually prepared via organic molecule sensitization. Despite the wealth of experimental studies on the 1O2-induced oxidation of several bio-organic molecules, the detailed mechanism of the oxidation process is largely unknown. Using high-level quantum chemical methods, we compute the potential energy profiles of the various electronic states associated with the [4 + 2]-cycloaddition reaction of O2 with a class of model peptide precursors that are based on derivatives of oxazole and thiazole. Experiments have shown that such oxazole/thiazole-based model peptides show a favorable reaction with 1O2. Upon increasing the molecular complexity, the bimolecular rate constant decreases and is attributed to the π-perturbing effects of the substituent of the oxazole/thiazole moiety. Our theoretical predictions are in excellent agreement with the experimental measurements and reveal a deep insight into the myriad electronic states that may hinder/promote the reaction of a given bio-organic molecule with 1O2.