Reactivity and Selectivity Patterns in Hydrogen Atom Transfer from Amino Acid C-H Bonds to the Cumyloxyl Radical: Polar Effects as a Rationale for the Preferential Reaction at Proline Residues

Absolute rate constants for hydrogen atom transfer (HAT) from the C-H bonds of N-Boc-protected amino acids to the cumyloxyl radical (CumO(center dot)) were measured by laser flash photolysis. With glycine, alanine, valine, norvaline, and tert-leucine, HAT occurs from the alpha-C-H bonds, and the stability of the alpha-carbon radical product plays a negligible role. With leucine, HAT from the alpha- and gamma-C-H bonds was observed. The higher k(H) value measured for proline was explained in terms of polar effects, with HAT that predominantly occurs from the delta-C-H bonds, providing a rationale for the previous observation that proline residues represent favored HAT sites in the reactions of peptides and proteins with OH. Preferential HAT from proline was also observed in the reactions of CumO with the dipeptides N-BocProGlyOH and N-BocGlyGlyOH. The rate constants measured for CumO were compared with the relative rates obtained previously for the corresponding reactions of different hydrogen-abstracting species. The behavior of CumO falls between those observed for the highly reactive radicals Cl and OH and the significantly more stable Br. Taken together, these results provide a general framework for the description of the factors that govern reactivity and selectivity patterns in HAT reactions from amino acid C-H bonds.