Theoretical studies on the structures of natural and alkylated cyclodextrins.

A series of semiempirical molecular orbital calculations using the AM1 method have been performed on isolated natural and alkylated alpha- and beta-cyclodextrins. For natural cyclodextrins, three geometries were considered: (i) molecular mechanics (MM2); (ii) AM1 fully optimized geometry; (iii) X-ray structures based on the experimental coordinates for heavy atoms with positions of hydrogen atoms optimized by AM1. Large differences between AM1 calculated properties of geometries i-iii were found. The differences between ii and iii are smaller and reflect the intermolecular, crystal packing forces. Comparisons are made between ii and iii and properties determined therefrom, such as cavity diameter, outer diameter, and height. In addition, AM1 semiempirical calculations were performed on the mixed (2,3,6) (hydroxyprophyl)-beta-cyclodextrin, 2,6-dimethyl-beta-cyclodextrin, and 2,6-bis(hydroxypropyl)-beta-cyclodextrin. The results were compared with the substituent effects on monoglucose. It was found that the alkylation and methyl and 2-(hydroxypropyl) functions on beta-cyclodextrin does not introduce significant steric hindrance.