Cheletropic decomposition of cyclic nitrosoamines revisited: the nature of the transition states and a critical role of the ring strain.

The cheletropic decompositions of 1-nitrosoaziridine (1), 1-nitroso-Delta(3)-pyrroline (2), 7-nitroso-7-azabicyclo[2.2. 1]hepta-2,5-diene (3), and 6-nitroso-6-azabicyclo[2.1.1]hexa-4-ene (4) have been studied theoretically using high level ab initio computations. Activation parameters of the decomposition of nitrosoaziridine 1 were obtained experimentally in heptane (DeltaH()(298) = 18.6 kcal mol(-)(1), DeltaS()(298) = -7.6 cal mol(-)(1) K(-)(1)) and methanol (20.3 kcal mol(-)(1), 0.3 cal mol(-)(1) K(-)(1)). Among employed theoretical methods (B3LYP, MP2, CCD, CCSD(T)//CCD), the B3LYP method in conjunction with 6-31+G, 6-311+G, and 6-311++G(3df,2pd) basis sets gives the best agreement with experimental data. It was found that typical N-nitrosoheterocycles 2-4 which have high N-N bond rotation barriers (>16 kcal mol(-)(1)) extrude nitrous oxide via a highly asynchronous transition state with a planar ring nitrogen atom. Nitrosoaziridine 1, with a low rotation barrier (<9 kcal mol(-)(1)) represents a special case. This compound can eliminate N(2)O via a low energy linear synperiplanar transition state (DeltaH()(298) = 20.6 kcal mol(-)(1), DeltaS()(298) = 2.5 cal mol(-)(1) K(-)(1)). Two higher energy transition states are also available. The B3LYP activation barriers of the cheletropic fragmentation of nitrosoheterocycles 2-4 decrease in the series: 2 (58 kcal mol(-)(1)) >> 3 (18 kcal mol(-)(1)) > 4 (12) kcal mol(-)(1). The relative strain energies increase in the same order: 2 (0 kcal mol(-)(1)) << 3 (39 kcal mol(-)(1)) < 4 (52 kcal mol(-)(1)). Comparison of the relative energies of 2-4 and their transition states on a common scale where the energy of nitrosopyrroline 2 is assumed as reference indicates that the thermal stability of the cyclic nitrosoamines toward cheletropic decomposition is almost entirely determined by the ring strain.

Effects of structure on alpha C-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)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.