Crystal structure of the low-humidity form of aspartame sweetener

The low-humidity IB crystal form of aspartame (L-alpha-aspartyl-L-phenylala nine methyl ester) is prepared via humidityinduced transition from the high ly hydrated IA crystal form and is used widely as a sweetener. The crystal structure of the low-humidity IB form is determined at 1.05 Angstrom resolu tion (0.476 Angstrom(-1) in maximum sin theta/lambda) from an extremely fin e fibrous crystal using synchrotron radiation. There are three aspartame mo lecules and two water molecules in the asymmetric unit of the monoclinic sp ace group P2(1). Each aspartame molecule adopts an almost identical extende d conformation which is commonly observed in other crystal forms of asparta me. Three aspartame molecules are assembled into a triangular trimer, and t rimer units are stacked along the b-axis via hydrogen-bonding and electrost atic interactions in the main chains and also via hydrophobic contacts in t he phenyl side-chains. Six trimer units are related by pseudo 6(1)-screw ax is symmetry and form a hydrophilic channel at their center. The hydrophilic channel in the is form contains only four water molecules in the unit cell , compared with 16 in the IA form. Although the IB form exhibits a trimer s tructure similar to that of the IA form, one aspartame molecule is rotated by approximate to 20 degrees from the orientation in the IA form. This arra ngement of the molecule implies that the humidity-induced transition is acc ompanied by a flapping motion of its methyl ester group. These structural d ifferences may imply the stepwise transition from the IA to the IB forms.