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 phi,psi angles similar to 180 degrees,similar to 180 degrees in ascending order, to an expected accuracy of +/-10 kJ mol(-1), are Asn 326; cystine 330; Asp 332; Gin 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; ne 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 similar to 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 phi,psi, angles. As a result the BDEs increase by about 10 kJ mol(-1) in beta-sheet and 40 kJ mol(-1) in alpha-helical environments, respectively. In effect the C-alpha-H BDEs can be "tuned" from about 345 to 400 kJ mol(-1) by adjusting the local environment. Some very significant effects of this are seen in the current literature on H-transfer processes in enzyme mechanisms and in oxidative damage to proteins. These observations are discussed in terms of the findings of the present study.