Prev. Article Next Article Table of Contents

Article

Effect of Side Chains on Competing Pathways for β-Scission Reactions of Peptide-Backbone Alkoxyl Radicals

Supporting Info

Geoffrey P. F. Wood,^†^‡ Christopher J. Easton,^‡^§ Arvi Rauk, Michael J. Davies,^‡ and Leo Radom*^†^‡

School of Chemistry, University of Sydney, Sydney, NSW 2006, Australia, Research School of Chemistry, Australian National University, Canberra, ACT 0200, Australia, Department of Chemistry, University of Calgary, Calgary, AB, T2N IN4 Canada, Heart Research Institute, Camperdown, Sydney, NSW 2050, Australia, and ARC Centre of Excellence in Free Radical Chemistry and Biotechnology

J. Phys. Chem. A, 2006, 110 (34), pp 10316–10323

DOI: 10.1021/jp062916j

Publication Date (Web): August 10, 2006

†

University of Sydney.

‡

Centre of Excellence in Free Radical Chemistry and Biotechnology.

Australian National University.

University of Calgary.

Heart Research Institute.

E-mail: radom@chem.usyd.edu.au.

Abstract

High-level quantum chemistry calculations have been carried out to investigate β-scission reactions of alkoxyl radicals located at the α-carbon of a peptide backbone. This type of alkoxyl radical may undergo three possible β-scission reactions, namely C−C β-scission of the backbone, C−N β-scission of the backbone, and C−R β-scission of the side chain. We find that the rates for the C−C β-scission reactions are all very fast, with rate constants of the order 10¹² s^-1 that are essentially independent of the side chain. The C−N β-scission reactions are all slow, with rate constants that range from 10^-0.7 to 10^-4.5 s^-1. The rates of the C−R β-scission reactions depend on the side chain and range from moderately fast (10⁷ s^-1) to very fast (10¹² s^-1). The rates of the C−R β-scission reactions correlate well with the relative stabilities of the resultant side-chain product radicals (•R), as reflected in calculated radical stabilization energies (RSEs). The order of stabilities for the side-chain fragment radicals for the natural amino acids is found to be Ala < Glu < Gln Leu Met Lys Arg < Asp Ile Asn Val < Ser Thr Cys < Phe Tyr His Trp. We predict that for side-chain C−R β-scission reactions to effectively compete with the backbone C−C β-scission reactions, the side-chain fragment radicals would generally need an RSE greater than 30 kJ mol^-1. Thus, the residues that may lead to competitive side-chain β-scission reactions are Ser, Thr, Cys, Phe, Tyr, His, and Trp.