Hydrogen abstraction by chlorine atom from amino acids: remarkable influence of polar effects on regioselectivity.

Quantum chemistry computations have been used to investigate hydrogen-atom abstraction by chlorine atom from protonated and N-acetylated amino acids. The results are consistent with the decreased reactivity at the backbone α-carbon and adjacent side-chain positions that is observed experimentally. The individual effects of NH(3)(+), COOH, and NHAc substituents have been examined and reveal important insights. The NH(3)(+) group in isolation is found to be deactivating at the α-position, while the acetamido group is activating. For the COOH group, polar effects lead to a contrathermodynamic deactivation of the thermodynamically most favorable α-abstraction. In the N-acetylamino acid, the α-position is deactivated by the combined inductive effect of the substituents and the presence of an early transition structure, again overriding the greater thermodynamic stability of the α-centered radical product. Deactivation of the α-, ß-, and γ-positions results in a peculiar stability for amino acids and peptides and their derivatives with respect to radical degradation.

Hydrogen abstraction by chlorine atom from small organic molecules containing amino acid functionalities: an assessment of theoretical procedures.

A high-level quantum chemistry investigation has been carried out for the abstraction by chlorine atom of hydrogen from methane and five monosubstituted methanes, chosen to reflect the chemical functionalities contained in amino acids and peptides. A modified W1' procedure is used to calculate benchmark barriers and reaction energies for the six reactions. The reactions demonstrate a broad range of barrier heights and reaction energies, which can be rationalized using curve-crossing and molecular orbital theory models. In addition, the performance of a range of computationally less demanding electronic structure methods is assessed for calculating the energy profiles for the six reactions. It is found that the G3X(MP2)-RAD procedure compares best with the W1' benchmark, demonstrating a mean absolute deviation (MAD) from W1' of 2.1 kJ mol(-1). The more economical RMP2/G3XLarge and UB2-PLYP/G3XLarge methods are also shown to perform well, with MADs from W1' of 2.9 and 3.0 kJ mol(-1), respectively.