Crystal and molecular structure of aspartame X HCl X 2H2O.

The crystal and molecular structure of the hydrochloride salt of the peptide sweetener aspartame (alpha-L-Asp-L-Phe methyl ester) has been determined at 120 K using 3877 reflections with I greater than 2.5 sigma I. Space group P2(1)2(1)2(1), cell dimensions a = 6.768(1), b = 9.796(1) and c = 26.520(3) A; final R factor 0.033. While the N-terminal L-Asp group in the structure of aspartame itself forms a six-membered ring with an intramolecular hydrogen bond between the carboxylate and the protonated amino terminus, the corresponding group in the hydrochloride adopts a completely different conformation with a weak intramolecular hydrogen bond between the carboxyl group and the N atom of the L-Phe residue. The L-Phe methyl ester moiety is rather similar in the two structures. Of the many possible conformations of aspartame, only one may be expected to function as a substrate at the receptor site for sweet taste, and a proposal is made for this active conformation.