Zwitterions - Introduction
Amino acids, peptides, and proteins typically contain both acidic and basic functional groups such as carboxyl and amino groups. Carboxylic acids with a pKa of ~5 can easily protonate an amine (pKb ~ 4) in aqueous solution and therefore molecules containing both carboxyl and amino groups are found to be zwitterions (both cations and anions) under near-neutral pH conditions. The reaction
in water is exothermic by ΔH° = -13 kcal/mol.
In the absence of solvent, in the gas phase, the same reaction (1) is
extremely endothermic by +144 kcal/mol.
The glycine zwitterion has been calculated to be unstable (no minimum
on potential surface) by ~18 kcal/mol.
However, solvating the glycine zwitterion with water molecules makes it
more stable than the solvated neutral form by ~11 kcal/mol.
Adding counter ions to zwitterions has a similarly stabilizing effect.
For instance, adding a sodium ion to glycine makes the zwitterion a stable
minimum on the potential energy surface, but it is still ~3 kcal/mol less
stable than the sodiated neutral glycine.
The effect of adding alkali ions to glycine has been extensively studied
by Hoyau and Ohanession,
who showed that the zwitterion structure is increasingly less stable with
increasing alkali ion size (Na+ through Cs+). (The
lithiated zwitterion does not follow this trend and is unusually unstable.)
In the most stable structures, Na+ is solvated by the nitrogen
and the carbonyl oxygen of neutral glycine (charge solvation structure
CS1), whereas the larger alkali ions Rb+ and Cs+
are bound to the two oxygens of neutral glycine (CS2). For K+
both structures CS1 and CS2 are about equally stable. Hence, in glycine-like
systems sodium is a good choice for stabilizing the zwitterion and only
a few kcal/mol are missing, which could potentially be gained by increasing
the proton affinity (PA) of the amine. Indeed it is found that for glycine-like
systems there is a fairly linear relationship between PA and the zwitterion
the PA by >5 kcal/mol over that of glycine makes the zwitterion the
most stable structure and hence, alpha-aminoisobutyric acid is found by
theory to be a zwitterion when sodiated. The linearity does not hold,
however, for N-amidino glycine, where the zwitterion is not as stable
as expected on the basis of the PA values, because the protonated guanidinium
group does not line up as perfectly with the dipole of the
Bowers group members who have worked on these projects include: