Hydrogen atom transfer polar effects

Reid DL, Armstrong DA, Rauk A, Nese C, Schuchmann MN, Westhoff U, von Sonntag C (2003) H-atom abstraction by C-centered radicals from cyclic and acyclic dipeptides. A theoretical and experimental study of reaction rates. Phys Chem Chem Phys 5 3278-3288 Roberts BP (1996) Understanding the rates of hydrogen abstraction reactions empirical, semi-em-pirical and ab initio approaches. J Chem Soc Perkin Trans 2 2719-2725 Russell GA (1973) Reactivity, selectivity, and polar effects in hydrogen atom transfer reactions. In Kochi JK (ed) Free radicals. Wiley, New York, pp 275-331 Russo-Caia C, Steenken S (2002) Photo- and radiation-chemical production of radical cations of methylbenzenes and benzyl alcohols and their reactivity in aqueous solution. Phys Chem Chem Phys 4 1478-1485... 

Russell, G. A. Reactivity, Selectivity and Polar Effects in Hydrogen Atom Transfer Reactions. In Free Radicals Koch, J. K., Ed. Wiley New York, 1973 Vol. I, pp. 275-331. 

In contrast to the case of tryptophan the photoreactions with tyrosine and histidine probably involve hydrogen atom transfer as the primary step. There are several indications for this. First, 0-methylated tyrosine (p-methoxy phenylalanine) did not show any photo-CIDNP effect and its reactivity as a photo-reductant towards flavins is strongly reduced (19). Similarly, 1-N-methyl histidine is not polarized at high pH (> 7.5), when no abstractable hydrogen is present. Secondly, in the protein ribonuclease A, which has a well known 3-dimensional structure, the residues Tyr 92 and His 105 have exposed rings, but their OH and NH protons are hydrogen bonded to backbone carbonyl groups. 

Marked contrasts in the effects of molecular structure on hydrogen-atom transfer reactions (equation 6) and the corresponding proton-transfer reactions (equation 2) have been found. The former reaction involves no change in charge (all species are univalent cations). Consequently polarization effects of hydrocarbon substituents are minimal, but large effects of delocalization of charge and spin densities in the cation radicals are observed. 

When the protonated amine-arm does not participate in the reaction (TS1-I ), the reaction is very endothermic. However, the activation barrier decreases to 2.6 kcal/mol and the endothermicity of the reaction becomes very small (only 0.2 kcal/mol), if the protonated amine-arm participates in the reaction (TS1-II). In this transition state the O-H distance is 1.709A, typical of a hydrogen bond. The origin of the acceleration was explained in terms of the enhancement of polarization of CO2 induced by the protonated amine arm, which increases the positive charge in the carbon atom. This polarization favors the electrostatic interaction between hydride and C02, and since this polarization increases the contribution of the C p orbital in the it orbital of C02, it favors also the charge-transfer from the H ligand to the 71 orbital of C02. In other paths starting with direct interaction between C02 and Ru the effect of the protonated amine was much smaller. 

Polar effects can also be important in atom transfer reactions. 4 In an oft-cited example (Scheme 13), the methyl radical attacks the weaker of the C—H bonds of propionic acid, probably more for reasons of bond strength than polar effects. However, the highly electrophilic chlorine radical attacks the stronger of the C—H bonds to avoid unfavorable polar interactions. As expected, the hydroxy hydrogen remains intact in both reactions. 

If a hydrogen atom is abstracted from an alkane by an alkyl radical, both the initial and final state of the reaction involve neutral species and it is only the transition state where some limited charge separation can be assumed. In the case of a homolytic O—H bond fission, however, the initial state possesses a certain polarity and possible changes in polarity during the reaction depend on both the lifetime of the transition state and the nature of the attacking radical. If the unpaired electron is localized mainly on oxygen in the reactant radical, the polarity of the final state will be close to that of the initial state and any solvent effect will primarily depend on the solvation of the transition state. Solvent effects can then be expected since the electron and proton transfers are not synchronous. 

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