Location: Plant Polymer ResearchTitle: DFTr studies of five and six residue Cyclic-beta(1 to 4) cellulosic molecules Author
Submitted to: Biopolymers
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 1/19/2012
Publication Date: 1/24/2012
Citation: Momany, F.A., Schnupf, U. 2012. DFTr studies of five and six residue Cyclic-beta(1 to 4) cellulosic molecules. Biopolymers. 97(1):568-576. Interpretive Summary: To create models of cellulosic materials one must consider that the polymer chains most likely reverse directions at some point in their crystal environment. It was suggested some years ago that they could carry this out by rotating the Phi'or'Psi glycosidic bond dihedral angles by 180 degree. Previous cutting edge calculations in this laboratory showed that this was a potential chain reversing event of low energy when carried out in vacuum. In fact when flipping three glycosidic dihedral angles in a row the polymer chain is reversed in direction. If one continues to flip this dihedral consecutively through five or six residue fragments, one creates polymers that have close contact from head to tail. Removing the equivalent of a water molecule from the two ends and creating a bond between the ends, converts these polymers to cyclic molecules which are very similar to well known and commercially valuable alpha-linked cyclodextrins. Today, cyclodextrins are sold worldwide in large quantities, thus our interest in the computational examination of these new beta-linked cyclic carbohydrates. Our calculations show that only specific structures are of low energy and most likely to be favored upon molecular synthesis. The cavities created by these cyclic 5- and 6-mers appear to be ideal for binding small drug molecules. This study is presented in an attempt to inspire new commercial applications of cellulosic materials.
Technical Abstract: Density functional (DFT) conformational in vacuo studies of cellobiose have shown that Phi-H-anti conformations are low in energy relative to the syn forms, while the Psi-H-anti forms are somewhat higher in relative energy. Further, as the cellulosic fragments became larger than a disaccharide and new hydrogen bonding interactions between multiple residues become available, stable low energy Phi-H-anti and Psi-H–anti cellulosic structures became possible. In order to test the stability of cyclic anti-conformations a number of Beta-linked cyclic molecules were created and energy optimized in solvent using the implicit hydration method, COSMO with water and n-heptane, and a reduced basis set (DFTr). Using dihedral angles (Phi-H/Psi-H) around the glycosidic bonds that produced low energy anti structures found from studies on cellobiose, it was possible to create five- and six-residue cyclic symmetric structures that were without distortion and could be energy optimized to stable energy minima. Upon optimization these 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 that these structures could exhibit strong synergistic tendencies, having networks of hydrogen bonds with all hydroxyl groups aligned in the same direction above and below the plane of the cyclic structure. 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 flipped conformations, that is, dihedral angles of ~180 degree/0 degree or ~0 degree/180 degree in Phi-H/Psi-H, it is clear that the synthesis of these compounds will be interesting.