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Abstract
This PhD thesis is divided into two sections, where the emphasis of the first section details the synthesis and development of small organic molecules as paramagnetic probes with applications in protein structure refinement. The second section involves the synthesis and characterization of a series of rhodium (I) complexes bearing functionalized tridentate pyrazolyl donor ligands and tridentate imidazolyl donor ligands. The reactivity of this series of rhodium (I) complexes towards intramolecular cyclization of alkynoic acids was investigated.
The synthesis of two thiol modified dipicolinic acid based tags, 4-mercaptomethyl-2,6-pyridinedicarboxylic acid (4MMDPA, 5) and 3-mercapto-2,6-pyridinedicarboxylic acid (3MDPA, 9) were described. The ligands 4MMDPA (5) and 3MDPA (9) were attached to the N-terminal domain of the arginine repressor from E. Coli. (ArgN). Lanthanide and transition metal complexes of the ArgN-4MMDPA and ArgN-3MDPA adduct were synthesized and large PCS were observed in the HSQC spectrum demonstrating their effectiveness as paramagnetic probes in protein structure refinement using NMR spectroscopy. A series of unnatural amino acids were synthesized and used as an alternative method to introduce paramagnetic probes without the need of post translational modification.
Rhodium (I) complexes bearing tridentate N,N donor ligands (pyrazole and imidazole) were syntheszied and was shown to bind to rhodium (I) in a bidentate (κ2) binding mode as shown by single crystal x-ray diffraction and variable temperature NMR spectroscopy. The activities of these complexes towards the intramolecular cyclization of aromatic and aliphatic alkynoic acids were investigated. Rhodium (I) complexes bearing imidazolyl donors were found to be highly active towards the cyclization of aliphatic and non-terminal aromatic substrates. Rhodium (I) complexes bearing pyrazolyl donors were found to be highly active towards terminal aromatic alkynoic acids. A hammett study was pursued to examine the influence of electronic nature of the terminal alkyne substituent but the results were inconclusive, however, it was found that electron withdrawing groups enhanced the rate of reaction.