Site specificity of α‐H abstraction reaction among secondary structure motif—An ab initio study

Abstract The initial step of protein oxidation is studied through α‐H abstraction by an OH radical with various secondary structure motifs of proteins. It is found that there exist preferential α‐Hs in this kind of abstractions. The typical abstraction mechanism involves three steps: forming a pre‐reactive complex before abstraction, the abstraction reaction, and the H 2 O detachment from a post‐reactive complex to form the product, C α ‐center radical. Using the stability of the pre‐reactive complex and the reaction barrier, we provide some explanation for this site preference. The feasibility of α‐H abstraction by OH radical depends not only on the types of secondary structure, but also on the reaction condition, such as in aqueous or in gas phase. Moreover, the reactivity of the abstraction also depends on the location of α‐H in the secondary structure motifs. The preferential α‐Hs to be abstracted in β‐sheet are those immediate to the amide or carbonyl group, and without involving hydrogen bonding, whereas in reverse turns, the preferential α‐Hs are near the C‐terminal of type I and near the N‐terminal of type II. In general, the α‐Hs in α‐helix are more difficult to be abstracted than those in β‐sheet and polypeptide in linear form. It is consistent with the trend of their bond dissociation energies. Our theoretical rate constant of N ‐acetyldiglycin‐methylamide (Ac(Gly) 2 NHCH 3 ) in aqueous solution (6.75 × 10 8 M −1 s −1 ) is close to the experimental observation of N‐ acetyldiglycinamide (Ac(Gly) 2 NH 2 ) (8.6 × 10 8 M −1 s −1 ). © 2007 Wiley Periodicals, Inc. J Comput Chem 28: 783–794, 2007