Application of solution state NMR to structural problems in chemistry

Abstract

First and foremost I would like to thank the Lord almighty for the life he has given me. My stay and study at Durham University was funded and supported by Canon Collins Trust to whom I am very thankful. I would also like to pass my gratitude to the National University of Lesotho for releasing me on staff development leave, my dependants’ allowance, and funding my travel both ways. I would like to thank my supervisory team: Dr. Alan M. Kenwright for his supervision and training and demonstrated kindness and patience. He motivated and encouradme during this period. I am also grateful to him for coming up with original ideas of a project on which I worked. Dr. John Sanderson cannot be forgotten for his co-supervisory role. I am also grateful to Dr. Elizabeth Grayson for the supervision in chemistry and for the protection and deprotection of the mannoside compounds. Dr. Louise Natrajan, I thank you for the lanthanide complexes I worked on. I would also like to thank Mr. Ian McKeag and Mrs Catherine Heffernan who contributed a lot to my training in solution state NMR. Other groups of people who contributed to my training need to be mentioned: all my lectures in the taught modules, the mass spectrometry facility and all the Chemistry Department staff. Last but not least my family members. Most importantly my wife and son who suffered the loneliness of my being thousands of miles away from them without complaint. Nuclear Magnetic Resonance (NMR) spectroscopy is a robust, non invasive technique applicable in structure determination as well as in the study of dynamic behaviour of chemical compounds. This thesis is in two sections, the first dealing mainly with a structure determination application of NMR and the second dealing mainly with a study of dynamic behaviour. Section 1 NMR characterisation of carbohydrates has proved challenging because of the limited chemical shift ranges of both the proton and carbon signals. The broad signals due to the labile hydroxyl protons cause further complications by overlapping proton signals from the ring. Protecting group chemistry is vital in the preparation and manipulation of synthetic carbohydrates and can potentially help with the assignment of the (otherwise extremely complicated) NMR spectra of carbohydrates. However, the widely used benzyl protecting group can make the spectrum more difficult to interpret because the benzyl CH2 proton signals often come in the same region of the spectrum as the anomeric protons, usually used as reporter groups of carbohydrates and the benzyl CH2 carbon signals come in the same region as the carbohydrate ring carbons. This section reports the invetsigation and application of a family of alternative protecting groups, namely various fluorobenzyl groups, which have not been used in carbohydrate chemistry before. With pentafluorobenzyl, the proton chemical shift dispersion is improved, and the CH2 and carbohydrate ring carbon signals are shifted to lower frequency, considerably simplifying the task of assigning the carbon spectrum, facilitating the interpretation of all 1H-13C correlation experiments (HSQC, HMQC, HMBC). Section 2 Cyclen complexes of lanthanide (III) ions have found use in magnetic resonance imaging (MRI), luminescence imaging and assay studies. In particular, europium (III) complexes have potential in anlytical, forensic, and biomedical applications based on their impressive emissive properties. However, the emissive properties are modulated by the thermodynamic stability and kinetic inertness of the complexes. For biomedical applications, chelation is necessary to avoid europium toxicity that may be triggerd by accidental dissociation of the complex and release of the metal in vivo. A new cyclen europium(III) complex with pyridyl pendant ligands instead of the usual acetate groups has been synthesised by a group at Manchester University. The pyridyl ligands confer higher emmisive intensities to the complex, to enable applicability of the complex in time gated measurements. The chemical structure determination of the compound was accomplished by 1H, 13C, COSY, HMQC / HSQC and EXSY NMR experiments. Selective inversion experiments data were evaluated using the CIFIT simulation program, and showed that in aqueous solutions from -0.2º C to 107.6º C the dominant dynamic process is flipping of the pendant (pyridyl) arms, and isomerism is biased towards the twisted square antiprism (TSAP).