DFTr Studies of Five‐ and Six‐Residue Cyclic‐β(1→4) Cellulosic Molecules

Abstract

Density functional (DFT) conformational in vacuo studies of cellobiose have shown that ϕ_H‐anticonformations are low in energy relative to the syn forms, while the ψ_H‐anti forms are higher in energy. Further, as the cellulosic fragments became larger than a disaccharide and new hydrogen bonding interactions between multiple residues become available, stable low energy ϕ_H‐anti and ψ_H––anti cellulosic structures became possible. In order to test the stability of cyclic anti‐conformations a number of β‐linked five‐ and six‐residue molecules were created and then energy optimized in solvent (water, n‐heptane) using the implicit solvation method COSMO at the B3LYP level of theory. The created symmetric cyclic structures were without distortion. Upon optimization some cyclic conformations were found to be of low energy when compared to linear five‐ and six‐residue chains, after correcting the energy for the exclusion of a water molecule upon cyclization. It was also obvious from the hydrogen bonding network formed above and below the plane of the cyclic structure that these structures could exhibit strong synergistic tendencies. The conformational energy preferences for clockwise ‘c’ and counter‐clockwise ‘r’ hydroxyl groups and preference for the hydroxymethyl rotamers is described. Because these structures contain energetically unfavorable flipped conformations in water, that is, dihedral angles of ∼180^o/0^o or ∼0^o/180^o in ϕ_H/ψ_H, it is clear that the synthesis of these compounds will be challenging. © 2012 Wiley Periodicals, Inc. Biopolymers, 2012