2011 Volume 10 Issue 3 Pages 88-97
We studied the properties of an inclusion complex of amoxicillin (AMPC) in a multifunctional-modified β-cyclodextrin (mf-βCD) having an affinity for bacteria. The mf-βCDs used were βCDs modified by the introduction, on the end of a hydrocarbon chain linker, of a saccharide or urea substituent group expected to have affinity for bacteria. Using quantum chemical methods, we showed that the use of mf-βCD stabilizes AMPC against acid, and that formation of an inclusion complex should produce bacterial affinity and improve bactericidal efficiency. The chemical stabilization of AMPC by mf-βCD was tested by hydrolysis. We also showed that in order to form a 1:1 complex of AMPC and mf-βCD (AMPC-mf-βCD) functioning as a drug delivery system (DDS), the optimal conditions require mixing mf-βCD with AMPC at a molar ratio between 1:5 and 1:10 (AMPC:mf-βCD). We used Gaussian program to determine the precedence of inclusion of AMPC by mf-βCDs and to obtain optimized structures of the complex. We demonstrated the importance of orbital interactions and electronic correlations during complexation for the emergence of chemotaxis in Helicobacter pylori1) toward the urea substituent on mf-βCDs. We further used the self-consistent reaction field (SCRF) method to study the effects of solvent. Using the optimized structures under solvent-free conditions, we calculated the energies of each AMPC-mf-βCD complex in water by the SCRF method using B3LYP/6-31G* levels.
