Modulation Of Water-Exchange Rates Of Lanthanide(iii)-Containing Complexes Using Polyethylene Glycol

<p> <strong>MODULATION OF WATER-EXCHANGE RATES OF LANTHANIDE(III)-CONTAINING COMPLEXES USING POLYETHYLENE GLYCOL</strong> </p> <p>by</p> <p> <strong>BUDDHIMA N. SIRIWARDENA-MAHANAMA</strong> </p> <p> <strong>May 2014</strong> </p> <p> <strong>Advisor:</strong> Dr. Matthew J. Allen</p> <p> <strong>Major:</strong> Chemistry </p> <p> <strong>Degree:</strong> Doctor of Philosophy</p> <p>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.</p>

Name thesis:degree_name

Ph.D.

Level thesis:degree_level

Open Access Dissertation

Discipline thesis:degree_discipline

Chemistry

Year dc:date.available

2014

Author dc:creator

• Siriwardena-Mahanama, Buddhima Nirodhi

Contributors dc:contributor

• Matthew J. Allen

• contrast agents
• lanthanide(III) complexes
• magnetic resonance imaging
• polyethylene glycol
• water-exchange rates
• Chemistry
• Inorganic Chemistry

Repository record dc:identifier

https://digitalcommons.wayne.edu/oa_dissertations/922

OAI identifier oai:identifier

oai:digitalcommons.wayne.edu:oa_dissertations-1921