The Stability of Cα Peptide Radicals: Why Glycyl Radical Enzymes?

The conformational space of dipeptide models derived from glycine, alanine, phenylalanine, proline, tyrosine, and cysteine has been searched extensively and compared with the corresponding C-alpha dipeptide radicals at the (MP2)-RAD level of theory. The results indicate that the (least-substituted) glycine dipeptide radical is the thermochemically most stable of these species. Analysis of the structural parameters indicates that this is due to repulsive interactions between the C-alpha substituents and peptide units in the radical. A comparison of the conformational preferences of dipeptide radicals and their closed-shell parents also indicates that radical stability is a strongly conformation-dependent property.