Effects of Structure on αC−H Bond Enthalpies of Amino Acid Residues: Relevance to H Transfers in Enzyme Mechanisms and in Protein Oxidation†

The bond dissociation enthalpies (BDE) of all of the amino acid residues, modeled by HC(O)NHCH(R)C(O)NH2 (PH(res)), were determined at the B3LYP/6-31G*//B3LYP/6-31G* level, coupled with isodesmic reactions. The results for neutral side chains with φ,ψ angles ∼180°,∼180° in ascending order, to an expected accuracy of ±10 kJ mol-1, are Asn 326; cystine 330; Asp 332; Gln 334; Trp 337; Arg 340; Lys 340; Met 343; His 344; Phe 344; Tyr 344; Leu 344; Ala 345; Cys 346; Ser 349; Gly 350; Ile 351; Val 352; Glu 354; Thr 357; Pro-cis 358; Pro-trans 369. BDEs calculated at the ROMP2/6-31G*//B3LYP/6-31G* level exhibit the same trends but are ∼7 kJ mol-1 higher. All BDEs are smaller than those of typical secondary or tertiary C−H bonds due to the phenomenon of captodative stabilization. The stabilization is reduced by changes in the φ,ψ angles. As a result the BDEs increase by about 10 kJ mol-1 in β-sheet and 40 kJ mol-1 in α-helical environments, respectively. In effect the αC−H BDEs can be “tuned” from about 345 to 40...