Characterization of aspartame-cyclodextrin complexation.
The inclusion complex formation of aspartame (guest) and various cyclodextrins (host) were examined using 1H NMR titration and capillary electrophoresis. Initially the protonation constants of aspartame were determined by NMR-pH titration with in situ pH measurement to yield log K1=7.83 and log K2=2.96. Based on these values the stability of the complexes formed by aspartame and 21 different cyclodextrins (CDs) were studied at pH 2.5, pH 5.2 and pH 9.0 values where aspartame exists predominantly in monocationic, zwitterionic and monoanionic form, respectively. The host cyclodextrin derivatives differed in various sidechains, degree of substitution, charge and purity so that the effect of these properties could be examined systematically. Concerning size, the seven-membered beta-cyclodextrin and its derivatives have been found to be the most suitable host molecules for complexation. Highest stability was observed for the acetylated derivative with a degree of substitution of 7. The purity of the CD enhanced the complexation while the degree of substitution did not provide obvious consequences. Finally, geometric aspects of the inclusion complex were assessed by 2D ROESY NMR and molecular modelling which proved that the guest's aromatic ring enters the wider end of the host cavity.
Sohajda
Tamás
T
Semmelweis University, Department of Pharmaceutical Chemistry, 1092 Budapest, Hogyes Endre u. 9, Hungary.
Béni
Szabolcs
S
Varga
Erzsébet
E
Iványi
Róbert
R
Rácz
Akos
A
Szente
Lajos
L
Noszál
Béla
B
D001218:Aspartame / Q000032:analysis / Q000737:chemistry*; D002412:Cations; D002626:Chemistry, Pharmaceutical / Q000379:methods*; D002942:Circular Dichroism; D019075:Electrophoresis, Capillary / Q000379:methods*; D006863:Hydrogen-Ion Concentration; D009682:Magnetic Resonance Spectroscopy / Q000379:methods*; D008958:Models, Molecular; D008968:Molecular Conformation; D015394:Molecular Structure; D011522:Protons; D047391:alpha-Cyclodextrins / Q000032:analysis / Q000737:chemistry*; D047392:beta-Cyclodextrins / Q000032:analysis / Q000737:chemistry*
D002412:Cations; D011522:Protons; D047391:alpha-Cyclodextrins; D047392:beta-Cyclodextrins; C031215:betadex; D001218:Aspartame; C032613:alpha-cyclodextrin