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Title: Paramagnetic probes for N.M.R. and E.S.R. study
Author: Mitchell, Dale Robert
Awarding Body: University of Leicester
Current Institution: University of Leicester
Date of Award: 1991
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Novel paramagnetic compounds, specifically nitroxyl radicals, were prepared and evaluated as possible contrast agents for Nuclear Magnetic Resonance (N.M.R.) imaging and as probes for Electron Spin Resonance (E.S.R.) spectroscopy. Attempts were made to target a nitroxyl radical to areas of calcification, particularly bone, in order to alter the local N.M.R. image. Several analogues of pyrophosphate are bone selective and have been used to prepare nucleotide analogues with altered phosphate chains. The novel pyrophosphate analogue N-oxy1-imidobisphosphonate, with a nitroxyl group bridging two phosphate groups, was synthesised. However, this nitroxyl was inherently unstable and could not be investigated further. The effects of sulphur atoms on bone specificity and the enzyme activity of nucleotide analogues were evaluated. This was achieved by preparing analogues of methylenebisphosphonate (a known bone agent) containing thiophosphonate groups. Methylenebisthiophosphonate and thiophosphonomethylphosphonate were both found to have poor bone selectivity. An ATP analogue was prepared with a methylenebisthiophosphonate group in the ?, ? position of the 5'-phosphate group. This was investigated as a competitive inhibitor of hexokinase with ATP. The possibility of attaching a nitroxyl radical to a bone specific agent was investigated. To this end a piperidinyl nitroxyl N-(l-oxyl-2,2,6,6,-tetramethyl-A-piperidinyl)-oxo- iminobisphosphonate, containing two phosphonate groups, was synthesised. However, this nitroxyl was not bone specific when administered in vivo and is currently awaiting trials as a contrast agent for N.M.R. imaging.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available