The bond dissociation enthalpies (BDE) of all of the amino acid residues, modeled by HC(O)NHCH(R)C(O)NH(2) (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 approximately 180 degrees, approximately 180 degrees 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 approximately 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 alpha C-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.

Ab initio methods have been employed to study the oxidation of the CH bonds in homo- (1a − d) and heterosubstituted alkanes (2a − d, 3a,b) by the parent dioxirane as a model for the dioxirane oxidation of proteins. The study involved methane (1a), ethane (1b), propane (1c), isobutane (1d), methylamine (2a), methanol (2b), ethanol (2c), acetaldehyde (2d), glycolaldehyde (3a), and a peptide model, N-formylglycine amide (3b). Geometries were optimized at DFT (B3LYP) and MP2 levels of theory using 6-31G* and 6-311+G** basis sets. Stationary points were characterized by vibrational frequency analysis. Final energies for the oxidation of 1a were obtained at the MP4(SDTQ)/6-311+G** and QCISD(T)/6-311+G** levels. A new mechanism of the oxidation reconciling the apparently contradictory experimental data was found. The reaction proceeds via a highly polar asynchronous transition state, which is common for either concerted oxygen insertion into the CH bond and formation of a radical pair (alkyl radical + α-hydroxyalkoxyl radical). These channels appear at a bifurcation point on the potential energy surface after the common transition state, which corresponds to formation of the new O−H bond, and ruptures of the C−H bond in the substrate and of the O−O bond in the dioxirane. The B3LYP theoretical model gives substantial hydride transfer character to the transition state and describes adequately the selectivity of the oxidation of hydrocarbons, alcohols, 1,2-diols, and leucine derivatives. The agreement with experimental data is further improved by taking into account the influence of a dielectric medium (IPCM model). The electrophilicity of dioxiranes in the oxidations of CH bonds implies that side groups of protected amino acids and proteins are more probable points for the attack of these oxidants than the weak α-CH bonds. It is of interest that selectivities of dioxirane oxidation are incorrectly predicted by the MP2 method, which overestimates the proton-transfer character of the transition state.

The Arrhenius parameters and rates of reaction of three hydroxyradicals, methyl radical, and the hindered primary C- centred radical from t-butyl alcohol with dithiothreitol were measured by pulse radiolysis in water. The bimolecular rate constants were found to be in the order: C-.(CH3)(2)OH > (CH)- C-.(CH3)OH > (CH2OH)-C-. > (.)CH3 > (CH2C)-C-.(CH3)(2)OH. The reaction of three of these, C-.(CH3)(2)OH, (CH2OH)-C-., and (CH3)-C-., with methanethiol were examined at the ab initio B3LYP/6311+G(d,p) level, coupled with transition state theory, both in the gas phase and in solution. The solvent effects are evaluated by two different continuum models (SCIPCM, CPCM), coupled with a novel approach to the calculation of the solution phase entropy. The reaction is discussed in terms of the charge and spin polarization in the transition state, as determined by AIM analysis, and in terms of orbital interaction theory. Rate constants, calculated by transition state theory are in good agreement with the experimental data

The stereochemistry of 1,2-H migration in ethylchlorocarbene (1) and chloromethylchlorocarbene (2) has been studied by ab initio methods. Geometries of the ground and transition states of a conformational equilibrium and the 1,2 rearrangement were optimized at the DFT (B3LYP) and MP2 levels of theory using 6-31G(D) and 6-311+G(D,P) basis sets. Final energies were obtained at the MP4/6-311+G(D,P)//MP2/6-311+G(D,P) level. It has been shown that the equilibrium between cis- and trans-conformers of 1 and 2 is shifted moderately toward the trans-conformer for carbene 1 and strongly toward the cis-conformer in the case of 2. The calculated barriers of rotation about the CC bond in carbene 1 (ΔG ⧧ = 2.3 kcal mol-1) and 2 (5.3 kcal mol-1) are lower than the smallest predicted barriers of the 1,2-H shift (8.0 and 8.5 kcal mol-1, respectively). In accordance with the Curtin−Hammett principle, kinetic control of stereochemistry of the rearrangement proceeding classically is realized. The predicted preferable formation of the Z-isomer of 1-chloropropene (3) and 1,2-dichloroethylene (4) is in good agreement with the experimental data obtained under conditions of the high-temperature thermolysis of the corresponding diazirines. Electronic factors influencing the relative stability of the cis- and trans-isomers of carbenes 1 and 2 and their transition states for 1,2-H migration are discussed.