Preparation,Structural Analysis And Molecular Modelling Of Drug-β-Cyclodextrin Inclusion Complexes

(3-Cyclodextrins and their derivatives have the medium-sized molecular weight, unique cage structure, hydrophobic interior and hydrophilic exterior, and these properties make them good drug carriers. The dissolvability of drug in water could be remarkably enhanced by forming inclusion complexes withβ-CDs. This has been widely used in the pharmaceutic field.Both sulfamethoxazole (SMZ) and trimethoprim (TMP) are board-spectrum antibiot-ics, combined to give an excellent antibiotic effect. But they are also hardly soluble in water and it restricts their clinic applications. In this study we prepared the inclusion complexes of them withβ-CD and twoβ-CD derivatives. The formation of inclusion complexes were confirmed by IR, XRD and NMR experiments. The stoichiometry of the complexes in water was studied to give a 1:1 ratio of the host-guest structure by NMR Job's method.The NMR ROESY experiments (rotating frame nuclear Overhauser effect) were carried out for all these inclusion compounds of SMZ or TMP withβ-CDs. The stable inclusion structures of SMZ andβ-CDs were proved by the observation of correlation peaks between hydrogen atoms of SMZ and hydrogen atoms of interior cavity ofβ-CDs. But for TMP such correlation peaks were not observed. It was presumed that the inclusion complexes were not stable or half-inserted in TMP andβ-CDs, or there was a fast dynamic exchange between dissociation and inclusion states.Molecular modelling encompasses all theoretical methods and computational techni-ques used to model or mimic the behaviour of molecules. The common feature of molecu-lar modelling techniques is the atomistic level description of the molecular systems; the lowest level of information is individual atoms (or a small group of atoms). Molecular docking is an method of molecular modelling, which studies intermolecular interactions in the host-guest system. AutoDock 4.2 was used to study the inclusion behaviour between SMZ (or TMP) withβ-CDs. The structures of inclusion complexes were displayed. The minimum energy configurations of top priority cluster were studied by cluster analysis method, their reasonableness of chemical structures were explained.