Intramolecular Hydrogen Bonds in Amino Acids.
-aminobutyric acid is physiologically important as an inhibitory neurotransmitter substance, and thus has been given a commonly used abbreviation: GABA. The neutral form of GABA forms a total of four conformers with O-H···N hydrogen bonds, which form two pairs of enantiomers. One of these enantiomer pairs exhibits an envelope structure with the COOH group, the nitrogen atom, and the carbon atoms and in one (slightly distorted) plane, whereas the other has carbon atoms and out of the plane of the COOH group, carbon atom , and the nitrogen atom. The hydrogen bonds are of different strength in these two pairs: stronger in the former, and weaker in the latter. The overlap of the fused spheres in the displays show this different strength clearly by the different amount of overlap.
As in glycine and -alanine, the H-bonded conformers are not the global minima of the
potential energy surface. The conformation of the global minima of GABA
is a straightforward extension of those of -alanine: the COOH group
and the carbon atoms and
are located in one plane, carbon
sticks out of that plane, and the amino group is oriented
towards the COOH group. Again, the interaction between the carbonyl
oxygen atom and the amino group hydrogen atom does not qualify as a
In fact, among the 62 symmetry-unique local
minima in the potential energy surface of GABA there is only one,
in which a N-H···O=C hydrogen bond is formed; the geometry
of this high-energetical conformer, which has the COOH-group in the
unfavourable trans-orientation, is shown next to this paragraph.
It should be noted, that this conformer and its enantiomer,
together with the conformers with the strong
N···H-O bond, are the only
hydrogen bonded conformers in the GABA potential energy surface.
As in -alanine, there are reaction paths that preserve the N···H-O hydrogen bond. In the case of GABA, there are two energetically different paths that connect the different H-bonded conformers in a closed cycle A-B-Am-Bm-A ("m" denoting mirror images). Each H-bonded conformer therefore has the "choice" between two different paths that do not break the hydrogen bond. In contrast to 3-aminoproanol, where there is a similar cycle of hydrogen bond conserving reactions, the reactions of the GABA cycle are the ones with the lowest potential barriers for both H-bonded conformers.