Structure, dynamics, and stability of beta-cyclodextrin inclusion complexes of aspartame and neotame.
Studies of the high-intensity sweetener aspartame show that its stability is significantly enhanced in the presence of beta-cyclodextrin (beta-CyD). At a 5:1 beta-CyD/aspartame molar ratio, the stability of aspartame is 42% greater in 4 mM phosphate buffer (pH 3.1) compared to solutions prepared without beta-CyD. Solution-state (1)H NMR experiments demonstrate the formation of 1:1 beta-CyD/aspartame complexes, stabilized by the interaction of the phenyl-ring protons of aspartame with the H3 and H5 protons of beta-CyD. Inclusion complex formation clearly accounts for the observed stability enhancement of aspartame in solution. The formation of inclusion complexes in solution is also demonstrated for beta-CyD and neotame, a structural derivative of aspartame containing an N-substituted 3,3-dimethylbutyl group. These complexes are stabilized by the interaction of beta-CyD with both phenyl-ring and dimethylbutyl protons. Solid-state NMR experiments provide additional characterization, clearly demonstrating the formation of inclusion complexes in lyophilized solids prepared from solutions of beta-CyD and either aspartame or neotame.
Garbow
J R
JR
Analytical Sciences Center, Pharmacia Corporation, 800 North Lindbergh Boulevard, St. Louis, Missouri 63167, USA. garbow@wuchem.wustl.edu
Likos
J J
JJ
Schroeder
S A
SA
D001218:Aspartame / Q000032:analysis / Q000737:chemistry*; D003505:Cyclodextrins / Q000032:analysis / Q000737:chemistry*; D004151:Dipeptides / Q000032:analysis / Q000737:chemistry*; D004355:Drug Stability; D006863:Hydrogen-Ion Concentration; D009682:Magnetic Resonance Spectroscopy; D013329:Structure-Activity Relationship; D013549:Sweetening Agents / Q000032:analysis / Q000737:chemistry*
D003505:Cyclodextrins; D004151:Dipeptides; D013549:Sweetening Agents; C404525:neotame; D001218:Aspartame