| Cyclodextrins (CDs) are cyclic oligosaccharides made up of six to twelveα-D-glucopyranose monomers connected at 1 and 4 carbon atoms. The most common naturally occurring cyclodextrins (CD) are composed of 6, 7 and 8α-1,4-linked D-glucopyranose and are usually referred to asα-,β- andγ-CD, respectively. They have the property of forming inclusion complexes with various guest molecules with suitable polarity and dimension because of their special molecular structure of hydrophobic internal cavity and hydrophilic external surface. They are widely used in pharmaceutical science , catalysis , separation technology, enzyme models and other areas.The focus of the present paper is to survey the progress that has been made in the use of QM and MD methods are now being used as tools for understanding the complexation process ofβ-CD chemistry. We will show, the structure, the bingding energy, the properties and the driving forces for the inclusion complexes of several organic molecules and drug molecules intoβ-cyclodextrin.The major novelties and conclusions can be summarized as follows:1. We have applied semiempirical PM3 calculations set on six kinds of benzene substituents into anhydrousβ-CD. Two different optimized structures of host were considered: hydroxyl groups point inside the molecule (host I), and point outside the molecule (host II). The statistical thermodynamic calculations proved that II is preferred in energy than I in the inclusion process. The driving forces for the complexation, and the geometry of the complexation were discussed in detail. 2. The inclusion process involvingβ-cyclodextrin (II) and p-substituted phenol has been investigated by using the PM3 method in vacuo. The p-bromophenol was proved to be the most favorable approach in passing through the cavity. Intermolecular hydrogen bond was confirmed by an independent theoretical calculation using AIM. The driving forces for the complex formation have been attributed to weak hydrogen bonding, the dipole dipole interactions, van der Waals interactions and hydrophobic interactions. It is showed that 1:1 guest/β-CD complex is favored by a negative enthalpy change.3. As hydroxyalkyl derivative, 2-Hydroxylpropyl-β-cyclodextrin (2-HPCD) can improve the biopharmaceutical performance of poorly watersoluble drug. In the present work, The inclusion process of 2-HPCD, as well as five reported drugs, was investigated at the semiempirical PM3 level. The two different orientation of secondary hydroxyl groups was considered in the host. The binding energy of inclusion showed that the secondary hydroxyl groups in the cavity of 2-HPCD was more favorable in energy than those outside the cavity in the inclusion process. it was concluded that the charge transfer interactions, dipole dipole interaction, host/guest interaction and hydrogen bonding are also discussed in this paper.4. The possible a, b orientation between 2-HPCD and five antimicrobial drug were analyzed by using molecular dynamics (MD). Solvent-solute interactions were also studied in our work. we discuss the size and conformation of 2-HPCD. It was proved that a high water solubility of 2-HPCD is owing to the more hydrophilic hydroxyl groups thanβ-CD. The calculations revealed that the interaction of 2-HPCD and drug can be strengthened through hydration pattern. According the MM/PBSA bingding energy, the inclusion complexation of spironolactone-2-HPCD are most energy favored in water, that is in good agreement with the vacuum data.
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