Biomedical subjects

Alfred D French

Publications and source records attributed to Alfred D French.

5 recordsLinked to original sources

PubMed2005

Determining the crystal structure of cellulose III(I) by modeling.

Recently, a one-chain monoclinic unit cell for cellulose III(I) having P2(1) symmetry and a single glucose in the asymmetric unit was proposed, based on high-resolution diffraction patterns. The new work challenged a two-chain structure that was published 25 years earlier, although it did not provide new three-dimensional coordinates. Our goals were to solve the structure by modeling, find whether modeling would reject the previously determined two-chain unit cell, and compare the model with the anticipated experimental structure. Combinations of three rotamers of the O-2, O-3, and O-6 hydroxyl groups produced 27 'up' and 27 'down' starting structures. Clusters ('minicrystals') of 13 cellotetraose chains terminated by methyl groups for each of the 54 starting structures were optimized with MM3(96). Hydroxyl groups on 16 of these 54 structures reoriented to give very similar hydrogen-bonding schemes in the interiors, along with the lowest energies. Hydrogen bonds included the usual intramolecular O-3H...O-5' linkage, with O-6' also accepting from O-3H. Interchain hydrogen bonds form an infinite, cooperative O-6H...O-2H...O-6 network. Direct comparison of total minicrystal energies for the one- and two-chain unit cell was inappropriate because the two-chain cell's alternate chains are shifted 0.9 A along the z-axis. To get comparable energy values, models were built with both cellotetraose and cellohexaose chains. The differences in their energies represent the energies for the central layers of cellobiose units. The one-chain cell models had much lower energy. The eight best 'up' one-chain models agree reasonably well with the structure newly determined by experiment.

Carbohydrate Conformation↗

PubMed2005

The external-anomeric torsional effect.

The rotational barrier for a methyl group at the end of an anomeric system is sometimes lower than we might have anticipated. Thus, in the trans-trans conformation of dimethoxymethane, the barrier to methyl rotation is calculated (B3LYP/6-311++G(2d,2p)) to be 2.22 kcal/mol, just slightly smaller than the corresponding barrier to rotation of the methyl group in methyl propyl ether of 2.32 kcal/mol. However, if the methyl being rotated in dimethoxymethane is placed into a gauche conformation, that rotational barrier is reduced to 1.52 kcal/mol. This substantial (0.80 kcal/mol relative to methyl propyl ether) reduction in barrier height in the latter case is attributed mainly to the change in the bond order of the C-O bond to which the methyl is attached, as a function of conformation, which in turn is a result of the anomeric effect. We have called this barrier lowering the external-anomeric torsional effect. This effect is apparently widespread in carbohydrates, and it results in the changing of conformational energies by up to about 2 kcal/mol. If polysaccharide potential surfaces are to be accurately mapped by molecular mechanics, this effect clearly needs to be accounted for.

Carbohydrate Conformation↗

PubMed2003

Incremented alkyl derivatives enhance collision induced glycosidic bond cleavage in mass spectrometry of disaccharides.

Electrospray ionization and collision induced dissociation on a triple quadrupole mass spectrometer were used to determine the effect of spatial crowding of incremented alkyl groups of two anomeric pairs of peralkylated (methyl to pentyl) disaccharides (maltose/cellobiose and isomaltose/gentiobiose). Protonated molecules were generated which underwent extensive fragmentation under low energy conditions. For both the 1 --> 4 and 1 --> 6 alpha and beta isomers, at comparable collision energies the methyl derivative exhibited the least fragmentation followed by ethyl, propyl, butyl, and pentyl. Collision energy is converted to rotational-vibrational modes in competition with bond cleavage, as represented by the slope of product/parent ion (D/P) ratio versus offset energy. Variable rotational freedom at the glycosidic linkage with incremented alkyl groups is hypothesized to be responsible for this effect. Discrimination of anomeric configuration was also assessed for these stereoiosmeric disaccharides. A systematic study showed that an increasing discrimination was attained for the 1 --> 4 isomeric pair as the size of the derivative increased from methyl to pentyl. No anomeric discrimination was attained for the 1 --> 6 isomeric pair. Parent and product ion scans confirmed the consistency of fragmentation pathways among derivatives. Chem-X and MM3 molecular modeling programs were used to obtain minimum energy structures and freedom of motion volumes for the permethylated disaccharides. The modeling results correlated with the fragmentation ratios obtained in the mass spectrometer giving strong indication that the collision induced spectra are dependent on the freedom of rotational motion around the glycosidic bond.

Algorithms↗

PubMed2002

Crystal structure of penta-O-acetyl-beta-D-galactopyranose with modeling of the conformation of the acetate groups.

The crystal structure of penta-O-acetyl-beta-D-galactopyranose was determined with Mo K(alpha) radiation at 150 K to R = 0.029. The space group is P2(1)2(1)2(1), and the unit cell dimensions are, a = 8.348, b = 9.021 and c = 25.418 A. The ring has the usual 4C(1) shape and O-6 is in the tg position as frequently observed for sugars having the axial galacto configuration at C-4. Conformations of the acetate groups were compared with those from the literature. Nearly eclipsed, 'Z' conformations are found for the ester moieties, and the torsion angles for the sequence involving the ring hydrogen, carbon, alkoxy oxygen and carbonyl carbon for both 1 and related compounds are eclipsed-to-gauche. Orientations and conformations of the acetate substituents were modeled with both MM3 molecular mechanics and various levels of quantum mechanics theory. Higher levels of theory and more complete models provided better prediction of the experimental observations.

Crystallization↗

PubMed2002

The crystal structure of the alpha-cellobiose.2 NaI.2 H(2)O complex in the context of related structures and conformational analysis.

The crystal structure of beta-D-glucopyranosyl-(1-->4)-alpha-D-glucopyranose (alpha-cellobiose) in a complex with water and NaI was determined with Mo K(alpha) radiation at 150 K to R=0.027. The space group is P2(1) and unit cell dimensions are a=9.0188, b=12.2536, c=10.9016 A, beta=97.162 degrees. There are no direct hydrogen bonds among cellobiose molecules, and the usual intramolecular hydrogen bond between O-3 and O-5' is replaced by a bridge involving Na+, O-3, O-5', and O-6'. Both Na+ have sixfold coordination. One I(-) accepts six donor hydroxyl groups and three C-H***I(-) hydrogen bonds. The other accepts three hydroxyls, one Na+, and five C-H***I(-) hydrogen bonds. Linkage torsion angles phi(O-5) and psi(C-5) are -73.6 and -105.3 degrees, respectively (phi(H)=47.1 degrees and psi(H)=14.6 degrees ), probably induced by the Na+ bridge. This conformation is in a separate cluster in phi,psi space from most similar linkages. Both C-6-O-H and C-6'-O-H are gg, while the C-6'-O-H groups from molecules not in the cluster have gt conformations. Hybrid molecular mechanics/quantum mechanics calculations show <1.2 kcal/mol strain for any of the small-molecule structures. Extrapolation of the NaI cellobiose geometry to a cellulose molecule gives a left-handed helix with 2.9 residues per turn. The energy map and small-molecule crystal structures imply that cellulose helices having 2.5 and 3.0 residues per turn are left-handed.

Carbohydrate Conformation↗