NMR Study on Inclusion Complexes of l -Phenylalanine and Aspartame with Cyclodextrins in Aqueous Solution

The interactions of Phenylalanine and Aspartame (N-l-α-Aspartyl-l-phenylalaninel-methyl ester, APM) with α- and β-cyclodextrins (CD) in aqueous solutions were investigated by 1H and 15N NMR techniques. The changes in chemical shift of CD protons on going from free CD to the mixture with phenylalanine and APM indicate that the phenyl ring is included in the cavity of CD in the complex states. The changes in the chemical shift of the β-protons of phenylalanine and APM following the binding to α- and β-CD indicate that the simple association constants (Ka) are not applicable to these systems except for the case of APM/β-CD (Ka=90), and that the large changes of the rotamer fractional population of APM side-chain occur for APM/β-CD system. The analysis with Asp–Phe(15N)–OMe suggests that the torsional angles of the main chain of APM are unchanged on the formation of the inclusion complex. The low-field shifts of amide proton and its nitrogen resonances of Asp–Phe(15N)–OMe in the complex formation suggest that the amide part of APM is hydrogen-bonded to the C2 or C3 hydroxyl group of β-CD.