Peptide cation-radicals.: A computational study of the competition between peptide N-Cα, bond cleavage and loss of the side chain in the [GlyPhe-NH2+2H]+• cation-radical

Cation-radicals and dications corresponding to hydrogen atom adducts to N-terminus-protonated N-alpha-glycylphenylalanine amide (Gly-Phe-NH2) are studied by combined density functional theory and Moller-Plesset perturbational computations (B3-MP2) as models for electron-capture dissociation of peptide bonds and elimination of side-chain groups in gas-phase peptide ions. Several structures are identified as local energy minima including isomeric aminoketyl cation-radicals, and hydrogen-bonded ion-radicals, and ylid-cation-radical complexes. The hydrogen-bonded complexes are substantially more stable than the classical aminoketyl structures. Dissociations of the peptide N-C-alpha bonds in aminoketyl cation-radicals are 18-47 kJ mol(-1) exothermic and require low activation energies to produce ion-radical complexes as stable intermediates. Loss of the side-chain benzyl group is calculated to be 44 kJ mol(-1) endothermic and requires 68 kJ mol(-1) activation energy. Rice-Ramsperger-Kassel-Marcus (RRKM) and transition-state theory (TST) calculations of unimolecular rate constants predict fast preferential N-C-alpha bond cleavage resulting in isomerization to ion-molecule complexes, while dissociation of the C-alpha-CH2C6H5 bond is much slower. Because of the very low activation energies, the peptide bond dissociations are predicted to be fast in peptide cation-radicals that have thermal (298 K) energies and thus behave ergodically. Copyright (C) 2003 John Wiley Sons, Ltd.