Hydrogen-Atom Abstraction from a Model Amino Acid: Dependence on the Attacking Radical

We have used computational chemistry to examine the reactivity of a model amino acid toward hydrogen abstraction by HO center dot, HOO center dot, and Br. The trends in the calculated condensed-phase (acetic acid) free energy barriers are in accord with experimental relative reactivities. Our calculations suggest that HO center dot is likely to be the abstracting species for reactions with hydrogen peroxide. For HO center dot abstractions, the barriers decrease as the site of reaction becomes more remote from the electron-withdrawing alpha-substituents, in accord with a diminishing polar deactivating effect. We find that the transition structures for alpha- and beta-abstractions have additional hydrogen-bonding interactions, which lead to lower gas-phase vibrationless electronic barriers at these positions. Such favorable interactions become less important in a polar solvent such as acetic acid, and this leads to larger calculated barriers when the effect of solvation is taken into account. For Br center dot abstractions, the alpha-barrier is the smallest while the beta-barrier is the largest, with the barrier gradually becoming smaller further along the side chain. We attribute the low barrier for the alpha-abstraction in this case to the partial reflection of the thermodynamic effect of the captodatively stabilized alpha-radical product in the more product-like transition structure, while the trend of decreasing barriers in the order beta > gamma > delta similar to epsilon is explained by the diminishing polar deactivating effect. More generally, the favorable influence of thermodynamic effects on the alpha-abstraction barrier is found to be smaller when the transition structure for hydrogen abstraction is earlier.