Vibrational Raman Optical Activity of Carbohydrates

Vibrational Raman optical activity (ROA), measured as a small differential Raman scattering of right and left circularly polarized incident light from chiral molecules, is emerging as a powerful new chiroptical probe of the solution stereochemistry of biopolymers. Only recently with the advent of CCD detection combined with a backscattering configuration has ROA achieved the sensitivity required for the acquisition of high quality biopolymer spectra. The work presented in this thesis represents the first concerted effort to acquire, assign and interpret the ROA spectra of carbohydrates ranging from monosaccharides to polysaccharides. The opening chapter of this thesis introduces the concept of optical activity as well as describing some conventional chiroptical techniques and contrasting the two complementary forms of vibrational optical activity: vibrational circular dichroism (VCD) and ROA. The following two chapters then deal with the fundamentals of the theory of ROA and the instrumentation required to measure it. Chapter 4 concentrates on the description of those aspects of carbohydrate stereochemistry that are required to appreciate the subsequent discussion of the ROA spectra. In addition, the main conventional physical methods of establishing carbohydrate conformation are briefly reviewed and the strength and weaknesses of each method noted. The next two chapters deal exclusively with the ROA of monosaccharides. Chapter 5 consists of a detailed study of D-glucose employing deuterated analogues to assign the ROA signals to particular vibrational coordinates where possible and to relate them to stereochemical features such as anomeric configuration, hydroxymethyl-1-group conformation and relative disposition of hydroxyl groups around the ring. Chapter 6 extends the work on the monosaccharides to the ketose sugars and the results are combined with earlier ROA studies to clarify some of the old assignments and establish new ones. In chapter 7 the ROA spectra of seven disaccharides of D-glucose with a range of different linkage types and configurations are presented. It is demonstrated that their ROA spectra contain a number of new signals sensitive to the conformation of the glycosidic link as well as many signals similar to those found in D-glucose itself. The final chapter concentrates on the ROA spectra of a number of cyclodextrins and polysaccharides as well as a single glycoprotein. The interpretation of these spectra emphasise the influence of the secondary structure through ROA signals that were identified in the preceding chapter as originating in the coordinates of the glycosidic link.