title: Hydrogen abstraction by chlorine atom from amino acids: remarkable influence of polar effects on regioselectivity.
abstract: Quantum chemistry computations have been used to investigate hydrogen-atom abstraction by chlorine atom from protonated and N-acetylated amino acids. The results are consistent with the decreased reactivity at the backbone α-carbon and adjacent side-chain positions that is observed experimentally. The individual effects of NH(3)(+), COOH, and NHAc substituents have been examined and reveal important insights. The NH(3)(+) group in isolation is found to be deactivating at the α-position, while the acetamido group is activating. For the COOH group, polar effects lead to a contrathermodynamic deactivation of the thermodynamically most favorable α-abstraction. In the N-acetylamino acid, the α-position is deactivated by the combined inductive effect of the substituents and the presence of an early transition structure, again overriding the greater thermodynamic stability of the α-centered radical product. Deactivation of the α-, β-, and γ-positions results in a peculiar stability for amino acids and peptides and their derivatives with respect to radical degradation.
authors.affiliation: ARC Centre of Excellence for Free Radical Chemistry and Biotechnology and School of Chemistry, University of Sydney, Sydney, NSW 2006, Australia.
authors.forename: Robert J
authors.initials: RJ
authors.lastname: O'Reilly
authors.forename: Bun
authors.initials: B
authors.lastname: Chan
authors.forename: Mark S
authors.initials: MS
authors.lastname: Taylor
authors.forename: Sandra
authors.initials: S
authors.lastname: Ivanic
authors.forename: George B
authors.initials: GB
authors.lastname: Bacskay
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: Easton
authors.forename: Leo
authors.initials: L
authors.lastname: Radom
mesh_terms: D000596:Amino Acids / Q000737:chemistry*; D002713:Chlorine / Q000737:chemistry*; D006859:Hydrogen / Q000737:chemistry*; D015394:Molecular Structure; D011789:Quantum Theory; D013237:Stereoisomerism; D013816:Thermodynamics
chemical_list: D000596:Amino Acids; D002713:Chlorine; D006859:Hydrogen