Oxidative damage to the glycyl α-carbon site in proteins: an ab initio study of the C—H bond dissociation energy and the reduction potential of the C-centered radical

The C—H bond dissociation energies (D C—H ) of a series of model glycyl proteins were derived from selected isodesmic reactions based on high level ab initio calculations. At 298 K, the recommended values of D C—H , in kJ mol −1 are: NH 2 CH 2 CHO, 308; NH 2 CH 2 C(O)NH 2 , 336; HC(O)NHCH 2 CHO, 331; HC(O)NHCH 2 C(O)NH 2 , 350; CH 3 C(O)NHCH 2 C(O)NH 2 , 347; HC(O)NHCH 2 C(O)NHCH 3 , 349; and CH 3 C(O)NHCH 2 C(O)NHCH 3 , 346. The average of the last four values, 348 kJ mol −1 , is the predicted bond dissociation energy of the α-C—H bond of a glycyl protein. The reduction potential in aqueous medium at 298 K and pH 7 for the process, R • + H + + e − = RH, where R • = XNHCH • C(O)Y and X and Y represent extension of the protein chain, is E 0 ′ 0.8 V. This result suggests that the α-C—H bond of a glycyl protein is susceptible to attack by RS • , ROO • , tyrosyl, and OH • radicals, whose reduction potentials for the analogous process are higher. The present study has established that the molecule HC(O)NHCHRC(O)NH 2 (R = an amino acid side chain) serves as an accurate model for the α-C environment of an amino acid residue in a protein, and that a reliable D C—H value for the α-C—H bond may be obtained from calculations on this model at the B3LYP/6-31G(D) level of theory in conjunction with an isodesmic reaction using neutral glycine as reference. Key words: glycine, peptide, amino acid, bond energy, radicals, ab initio, computation.