Submitted to: Carbohydrate Research
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: February 23, 2007
Publication Date: July 2, 2007
Citation: French, A.D., Johnson, G.P. 2007. Linkage and pryanosyl ring twisting in cyclodextrins. Carbohydrate Research. v. 342(9). p. 1223-1237. Interpretive Summary: Cyclodextrin molecules consist of five or more glucose rings that are connected head-to-tail to make larger rings. These molecules, made from starch, are useful because there is often a cavity inside the ring that can hold guest molecules. These guests can be either fragrance, drug or pesticide molecules that are to be released very slowly, or the cyclodextrin can absorb unwanted molecules from an environment. Because the cyclodextrins are derived from starch and are often highly crystalline, they can be used as models to learn how carbohydrate molecules interact with other molecules. This is useful because crystals of actual starch do not furnish information at high resolution. The crystals of cyclodextrin also provide information about the precise details of carbohydrate materials that can be compared with computer models of the carbohydrate for tests of accuracy of the models. When examining high-resolution molecular structures of cyclodextrins, a new, twisting deformation of the glucose molecules was discovered, and modeling studies gave a new understanding of the basis for the sometimes twisted shapes of the cyclodextrins. This fundamental information is of interest to scientists concerned with the atomic levels of interaction with carbohydrate materials. In molecules such as cellulose and starch, these deformations are most likely to occur in the non-crystalline regions where much of the useful chemistry occurs.
Technical Abstract: Crystalline acylated cyclodextrins (CDs) in the literature were studied to gain perspective on maltose octapropanoate in the preceding paper. That led to studies of other CDs and to increased understanding of distortion in CDs and, ultimately, non-crystalline regions in starch. Classic CDs have six to eight glucose residues in the shape of a truncated cone or doughnut, stabilized by a ring of O3- - O2' hydrogen bonds. On a phi, psi energy map for a maltose analog that does not form hydrogen bonds, such CD shapes have higher energy than a nearby region favored by the exoanomeric effect. Derivatized CDs with seven residues (CD7s) are distorted with some linkages better stabilized by the exoanomeric effect (and acyl stacking if available), leading to local left-handed helical geometry. Other linkages in the same macrocycle provide counter-balancing right-handed helical tendencies, but with increased potential energy. Permethylated CDs with eight residues (CD8s) have two "flipping" linkages as do examples of larger CDs. Those flipping linkages allow for the joining of two left-handed helical segments into a macrocycle, letting all linkages conform to the exoanomeric effect better than in classic CDs. Glucose rings in derivatized CD7s have substantial positive twists of the pseudo torsion angle O1–C1- -C4–O4, adding more right-handed helical character to balance the left-handedness of linkages stabilized by the exoanomeric effect. In substituted CD8s residues, the residues have large negative twists, giving extra left-handed character to the short, pseudohelical segments. In non-macrocyclic molecules the twist ranged from –14 to +2 , averaging –6.23. In the selected CDs, the twist ranged from –22 to +12 for 4C1 rings, and the OS2 ring in acetylated CD7 has a value of +35. Such a twist in a 4C1 ring would have a high energy. Glucose residues in larger CDs are less twisted.