Solvation of the Glycyl Radical.

The effect of adding explicit water molecules to the neutral (N) and zwitterionic (Z) forms of the glycyl radical has been examined. The results show that a minimum of three water molecules is required to stabilize the Z radical as a local minimum, with an energy gap of 123 kJ mol between the N and Z forms at this point, in favor of the N form. Increasing the number of water molecules to ∼20 leads to a converged Z-N energy difference of ∼50 kJ mol still in favor of the N form, even though the radical is not considered fully solvated from a structural point of view. Thus, energetic convergence is determined mainly by solvation of the polar functional groups, and a complete coverage of the entire molecule is not necessary. Because aqueous closed-shell glycine exists as a zwitterion while aqueous glycyl radical prefers the neutral form, the conversion between the two necessitates a change along the hydrogen-abstraction reaction pathway. In this regard, the transition structure for α-hydrogen abstraction by the ·OH radical has greater resemblance to glycine than to the glycyl radical. Overall, the barrier for hydrogen abstraction from Z glycine is larger than that from the N isomer, and this might act to provide some protection against radical damage to the free amino acid in the (aqueous) biological environment.