Open Access Dissertation
Date of Award
Matthew J. Allen
MODULATION OF WATER-EXCHANGE RATES OF LANTHANIDE(III)-CONTAINING COMPLEXES USING POLYETHYLENE GLYCOL
BUDDHIMA N. SIRIWARDENA-MAHANAMA
Advisor: Dr. Matthew J. Allen
Degree: Doctor of Philosophy
A modular system of lanthanide(III)-containing polyethylene glycol (PEG) conjugates was synthesized and characterized to investigate the influence of length and density of PEG on water-exchange rates of lanthanide(III)-containing complexes. The water-exchange rates of lanthanide(III)-containing complexes contribute to the efficiency of these complexes as T1-shortening and paramagnetic chemical exchange saturation transfer (PARACEST) contrast agents for magnetic resonance imaging (MRI). Because the mechanism of these two MRI methods is vastly different, there is a need to tune the water-exchange rates of lanthanide(III)-containing complexes over a broad range: towards fast rates (108 s-1) for T1-shortening agents and slow rates (103 s-1) for PARACEST agents. As a result, extensive research efforts have contributed to tuning water-exchange rates of both types of contrast agents using coordination-chemistry-based strategies. These studies reveal that small modifications in the structure of lanthanide(III)-containing complexes lead to considerable changes in water-exchange rates. This thesis tests the hypothesis that hydrophilic PEG alters the accessibility of bulk water and the extent of hydrogen bonding between lanthanide(III)-coordinated and bulk water. To test this hypothesis, a PEG-based lanthanide(III)-containing model system was designed and synthesized to investigate the influence of length and density of PEG on the water-exchange rates of lanthanide(III)-containing complexes. Properties of the new complexes that are relevant to MRI, including water-exchange rates, were determined using relaxometric and spectroscopic techniques. The modular lanthanide(III)-containing system designed to investigate the influence of length of PEG demonstrated that PEG is able to tune water-exchange rates of lanthanide(III)-containing polyaminopolycarboxylate-type complexes toward slower rates. The ability of PEG to tune water-exchange rates toward slower rates as a function of the length of PEG is likely due to the variation in extent of hydrogen bonding between coordinated and bulk water. These findings provide insight into the influence of length and density of PEG on water-exchange rate and contrast agent efficiency and are expected to be useful in the design of contrast agents with optimum water-exchange rates.
Siriwardena-Mahanama, Buddhima Nirodhi, "Modulation Of Water-Exchange Rates Of Lanthanide(iii)-Containing Complexes Using Polyethylene Glycol" (2014). Wayne State University Dissertations. 922.