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The factors influencing the rate of isomerization of alkyl radicals is investigated using ab initio calculations on the example of the 2-methylhexyl radical. The equilibrium geometries of the isomers and the transition structures of 16 isomerization channels connecting them are determined at the UHF/6-31G* level. The isomerization energies and barrier heights are calculated at the MP-SAC2/6-311G** level. The most stable isomer is the tertiary radical, less stable are the secondary isomers, and the least stable are the primary isomers of the 2-methylhexyl radical, the largest energy difference being about 3.5 kcal mol-1. The heights of the barriers separating the isomers depend on the relative location of the radical center before and after the reaction. The barrier height for 1,2 as well as 1,3 H atom transfer is about 37−40 kcal mol-1, that for the 1,4, 1,5, and 1,6 isomerizations is lower, about 20, 13, and 15 kcal mol-1, respectively. The height of the barrier, and, accordingly, the activation energy vary by about 2 or 3 kcal mol-1 depending on the substitution in the ring of the cyclic transition structure and the concomitant change of the reaction enthalpy. Our RRKM calculations show that the fastest isomerization reaction is the 1,5 H atom transfer taking place through a six-membered cyclic transition structure. The relative importance of 1,4 and 1,6 H atom transfers to that of 1,5 isomerization, however, being dependent on the pressure and temperature, may not be negligible, and they together may exceed 30%.

Ab initio calculations were performed on prototypical intramolecular H atom transfer reactions in alkyl radicals, namely, the identity reactions of 1,2-, 1,3-, 1,4-, and 1,5 intramolecular isomerizations in the ethyl, 1-propyl, 1-butyl, and 1-pentyl radicals, respectively. The equilibrium geometries and the transition structures have been optimized at the UHF/6-31G* and/or UMP2/6-311G** levels. The activation energies at 0 K were calculated with the MP-SAC2 and BAC-MP4 methods. The computed barrier heights (41.1, 41.6, 24.6, 17.2 kcal mol-1 at the MP-SAC2 and 43.1, 41.0, 25.1, and 18.8 kcal mol-1 at the BAC-MP4 level of theory) follow the trend expected and are in reasonable agreement with experimental data on related reactions. The differences between the ab initio barrier heights of alkyl isomerizations and that of the corresponding bimolecular reaction are in good agreement with the strain energies of the corresponding cycloalkanes.

The geometries and standard enthalpies of formation (∆ f H°) of 4 paraffins and 31 alkyl radicals at 298 K were obtained by means of complete basis set 4 (CBS-4) ab initio molecular orbital theory. A comparison of the geometry of a molecule and the radicals derivable from it via elimination of a H atom from different positions suggests that only a negligible change occurs in the geometry of the groups immediately adjacent to the radical center. The CBS-4 ∆ f H°s scaled by an empirical correction display an average deviation of 0.4 kcal mol -1 from the experimental data. Group values (GVs) were evaluated from the corrected ab initio ∆ f H°s by simultaneous parameter estimation. The group additivity (GA) rule was checked by a statistical analysis of the theoretical data. The derived GVs describe the corrected ab initio ∆ f H°s with an average deviation of less than 0.3 kcal mol -1 , which indicates that the GA rule is applicable to alkyl radicals, and the ∆ f H°s of alkyl radicals can be predicted with an accuracy similar to that attained with existing experimental methods. New values of radical, radical-adjacent, and (C) 2 -C-C ˙-(C) gauche GVs are suggested; together with the accepted alkane GVs, these yield accurate ∆ f H°s of alkyl radicals within estimated errors of 0.5 kcal mol -1 . Application of the GVs derived from small species is predicted to perform less satisfactorily in the estimation of ∆ f H°s of C 4 -C 6 species: the average deviation increases from 0.3 to 0.6 kcal mol -1 , while the correlation of the individual deviations and carbon numbers of the alkyl radicals changes from nearly zero to -0.36.

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Overproduction of reactive oxygen species in aging tissues has been implicated in the pathogenesis of aging-associated cardiovascular dysfunction. Oxidant-induced DNA-damage activates the poly(ADP-ribose) polymerase (PARP) pathway, leading to tissue injury. In this study we investigated the acute effects of the PARP inhibitor INO-1001 on aging-associated cardiac and endothelial dysfunction. Using a pressure-volume conductance catheter, left ventricular pressure-volume analysis of young and aging rats was performed before and after a single injection of INO-1001. Endothelium-dependent and -independent vasorelaxation of isolated aortic rings were investigated by using acetylcholine and sodium nitroprusside. Aging animals showed a marked reduction of myocardial contractility and endothelium-dependent relaxant responsiveness of aortic rings. Single dose INO-1001-treatment resulted in acute improvement in their cardiac and endothelial function. Immunohistochemistry for nitrotyrosine and poly(ADP-ribose) confirmed enhanced nitro-oxidative stress and PARP-activation in aging animals. Acute treatment with INO-1001 decreased PARP-activation, but did not affect nitrotyrosine-immunoreactivity. Our results demonstrate that the aging-associated chronic cardiovascular dysfunction can be improved, at least, short term, by a single treatment course with a PARP-inhibitor, supporting the role of the nitro-oxidative stress -- PARP -- pathway in the age-related functional decline of the cardiovascular system. Pharmacological inhibition of PARP may represent a novel therapeutic utility to improve aging-associated cardiovascular dysfunction.

The use of fibular free flaps has become established as a reliable and popular method for reconstruction of segmental mandibular defects. The role of routine preoperative angiography remains controversial. Sixty four digital subtraction angiograms were studied in a series of 39 consecutive patients clinically judged to be satisfactory candidates for fibula free transfer. Angiographic findings revealed vascular anomalies in 10 extremities (15.6%). Regarding the high potential for significant donor site morbidity authors consider vascular imaging essential part of preoperative evaluation.