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–1 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–1 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.