Spectroscopy And Molecular Modeling Studies Of Chloramphenicol-Cyclodextrin Inclusion Complex

Cyclodextrins (CDs) are cyclic oligosaccharides, consisting of six to twelve D-glucose monomers connected by a-(1,4) bonds. The most widely used CDs are a-,β-,andγ-CD with 6,7,8 D-glucopyranose units respectively. They can form inclusion complex with various guest molecules. Inclusion complex can modify the properties of guest molecules, such as the improved solubility of poorly soluble drugs,the enhanced chemical stability,the covered undesirable odor and so on.Chloramphenicol is an antibacterial drug,which is slightly soluble in water,bitter in taste.While complexed into CDs,its solubility is enhanced and bitter taste is covered up.This article studied on chloramphenicol-cyclodextrin inclusion complexes by spectroscopic analysis and molecular modeling.Stoichiometries and stability constants of chloramphenicol with a-CD,β-CD, y-CD were studied by modified Benesi-Hildebrand equation,which showed the formation of 1:1 stoichiometry with stability constants 13 M-',205 M-1,36 M-1 respectively. And the results of phase solubility method showed that chloramphenicol formed 1:1 stoichiometry with 2,6-DMβCD,with stability constant 492 M-1.These results demonstrated that 2,6-DMβCD had strongest inclusion ability for chloramphenicol.These inclusion complexes were confirmed by UV,CD,IR and NMR.The results showed that the benzene ring of chloramphenicol was included in the cavity of CDs.The structures of chloramphenicol-β-CD inclusion complex and chloramphenicol-2,6-DMβCD inclusion complex were simulated by semi-emprical PM3 method.The results showed that the structures were similar with each other, with the benzene ring in the CDs cavity and NO2 segment near the wide rim of CDs. The structures obtained from the molecular modeling were in agreenment with the experiment results. NBO analysis showed that there were one strong H-bond strong,two weak H-bonds and eight very weak H-bonds for chloramphenicol-β-CD complex and one strong H-bond strong and four very weak H-bonds for chloramphenicol-2,6-DMβCD complex.