Linkage and pyranosyl ring twisting in cyclodextrins

Acylated β-cyclodextrins (β-CDs) were studied to gain perspective on maltose octapropanoate, the crystal structure of which was reported in the preceding paper in this issue. Acylated β-CDs are distorted so we looked at other CDs and gained increased understanding of distortion in CDs and possibly, shapes in starch. Classic CDs have six to eight glucose residues in a doughnut shape that is stabilized by a ring of inter-residue O3⋯O2′ hydrogen bonds. On a ϕ,ψ energy map for a maltose analog that does not form hydrogen bonds, classic CD linkages have higher energies than structures that are stabilized by the exo-anomeric effect. In distorted β-CDs, which lack hydrogen bonding, some linkages attain low-energies from the exo-anomeric effect and acyl stacking. Those linkages result in left-handed helical geometry so other linkages are forced by the CD macrocycle to have counter-balancing right-handed character. Permethylated γ-CDs have two ‘flipping’ linkages as do some larger native CDs. Flipping linkages allow two left-handed segments to join into a macrocycle, thus avoiding the higher-energy, right-handed forms. Some glucose rings in derivatized β-CDs have substantial positive twists of the pseudo torsion angle O1–C1⋯C4–O4, adding right-handed character to balance the left-handed linkages. In substituted γ-CD, all residues have negative twists, giving extra left-handed character to the short, pseudo-helical segments. In non-macrocyclic molecules the twists ranged from −14° to +2°, averaging −6.1°. In these β- and γ-CDs, the twists ranged from −22° to +16° for 4C1 rings, and the OS2 ring in acetylated β-CD has a twist of +34°. Glucose residues in other CDs were less twisted.

Figure optionsDownload as PowerPoint slide