Abstract

NMR diffusion coefficient measurements and PM3 theoretical calculations were employed in the study of the inclusion complexation of allopurinol with ?-cyclodextrin (?-CD) at pH 6.5 and 10.0. Experimental findings revealed an increase in the association constant from 16 to 30 M-1 as a consequence of guest deprotonation. PM3 quantum-mechanical calculations were performed to investigate the complexation process between ?-CD and allopurinol, considering the most stable neutral and anionic tautomers of the guest. The binding energies obtained from the computational study were in agreement with the experimental observations, indicating that the anionic complex was more stable than the neutral one. Such unusual behavior was related to hydrogen bonding interactions between ?-CD and the anionic guest, leading to the increase of the association constant as a consequence of guest deprotonation. © Springer Science+Business Media, Inc. 2006.