Intermediate state during the crystal transition in aspartame, studied with thermal analysis, solid-state NMR, and molecular dynamics simulation

Aspartame (L-alpha-aspartyl-L-phenylalanine methyl ester) is a dipeptide sw eetener about 200 times as sweet as sugar. it exists in crystal forms such as IA, IB, IIA, and IIB, which differ in crystal structure and in the degre e of hydration. Among these, IIA is the most stable crystal form, and its c rystal structure has been well determined (Hatada ct al., J. Am. Chern. Sec ., 107, 4279-1282 (1985)), To elucidate the structural factors of thermal s tability in the IIA form of aspartame and to examine the physical process i n the crystal transformation between the IIA and IIB forms, we performed a thermal analysis and solid-state NR IR measurements. We found that a quasi- stable intermediate state exists in the transformation, and it has the same crystal lattice as the usual IIA form, despite the dehydration from 1/2 mo l to 113 mol per 1 mol of aspartame, The results of the energy component an alysis and the molecular dynamics simulation suggest that the entropic effe ct promotes the generation of the intermediate state, which is presumably c aused by the evaporation of the water of crystallization and the increase o f molecular motion in aspartame, Thus, the thermal stability of the IIA for m is attributable to a structural property, i.e., the crystal lattice itsel f is retained during the above dehydration. Moreover, the molecular dynamic s simulations suggest that the aspartame molecules have two kinds of confor mational flexibility in the intermediate state.