Modeling β-Scission Reactions of Peptide Backbone Alkoxy Radicals:  Backbone C-C Bond Fission

To model the C-C β-scission reactions of backbone peptide alkoxy radicals, enthalpies and barriers for the fragmentation of four substituted alkoxy radicals have been calculated with a variety of ab initio molecular orbital theory and density functional theory procedures. The high-level methods examined include CBS-QB3, variants of the G3 family, and W1. Simpler methods include HF, MP2, QCISD, B3-LYP, BMK, and MPW1K with a range of basis sets. We find that good accuracy can be achieved with the G3(MP2)//B3-LYP and G3X(MP2)-RAD methods. Lower-cost methods producing reasonable results are single-point energy calculations with UB3-LYP/6-311+G(3df,2p), RB3-LYP/6-311+G(3df,2p), UBMK/6-311+G(3df,2p), and RBMK/6-311+G(3df,2p) on geometries optimized with UB3-LYP/6-31G(d) or UBMK/6-31G(d). Heats of formation at 0 K for the alkoxy radicals and their fragmentation products were also calculated. We predict ΔfH0 values for the alkoxy radicals of -71.4 ((•)OCH2CH [Formula: see text] O), -102.5 ((•)OCH(CH3)CH [Formula: see text] O), -176.6 ((•)OCH(CH3)C(NH2) [Formula: see text] O), and -264.6 ((•)OC(CH3)(NHCH [Formula: see text] O)CH [Formula: see text] O) kJ mol(-)(1). For the fragmentation products NH2C((•)) [Formula: see text] O and CH( [Formula: see text] O)NHC(CH3) [Formula: see text] O, we predict ΔfH0 values of -5.9 kJ mol(-)(1) and -352.8 kJ mol(-)(1).