A stereoelectronic and thermodynamic study of b-D-methyl glucose conformational changes related to anomeric centre reactivity
The major part of this thesis focuses on investigating the rationale for ring deformation of -D-methyl glucose in glycosidase reactions (for example, cellulose hydrolysis). The investigation is computational and is done in isolation from the enzyme binding pocket and incoming nucleophile. What is the effect of the C1-O1 bond breaking process on key glucose properties is the central question asked and answered in this thesis. A battery of ab initio methods is used to uncover details of the glucose ring pucker free energy volumes. The free energy volumes were computed using the Free Energy from Adaptive Reaction Coordinate Forces (FEARCF) method. The bond stretch of the C1-O1 bond in -D-methyl glucose serves as a sugar model for hydrolysis, following the DN*AN mechanism. The FEARCF method has been employed as it was previously shown to generate molecular sampling traversing all of pucker phase space resulting in a multidimensional free energy surfaces (or volumes). Density functional theory and post SCF analysis have been used to investigate the stereoelectronic changes that occur during ring deformation. In particular, changes involving the anomeric carbon, that is the C1-O1, C1-O5 bond distances, electron densities and charges of the C1, O5 and O1 atoms.
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