A series of lanthanide complexes, {[CpCo(P=O(OR)2)3]2Ln(H2O)x}+Cl- (Ln = Nd, Eu, Tb, Yb; R = Et, Ph), (Kläui)2Ln, were prepared. The related complex {[CpCo(P=O(OPh)2)3]2Yb}+ [CoCl3(THF)]- was crystallographically characterized and the cation in this case was confirmed to be 6-coordinate and solvent free. To determine the Kläui complexes potential as magnetic resonance (MR) imaging agents, ligand exchange rates between the d0- and d60-isotopomers of the Kläui lanthanide complexes were determined in acetonitrile by electrospray mass spectrometry. The ligand exchange rate was found to increase by almost 4-orders of magnitude from the smallest (Yb) to largest ion (Nd) in acetonitrile. Additionally, the ligand exchange rate increased rapidly for the Tb complex with increasing water concentration. Changing the phosphite substituent had no significant impact on the rate of ligand exchange for R = Ph relative to R = Et. Modification to the phosphite substituents to decrease ligand exchange was unsuccessful indicating that these ligands were not suitable as MR imaging agents.
Oxazoline based ligands are known to complex lanthanide ions, however, most of these complexes undergo rapid ligand exchange when not in water solution. Several novel oxazoline based ligands with increased chelation to stop ligand exchange were designed. During the course of their synthesis it was discovered that these ligands were too unstable to be used in vivo and this ligand set was abandoned for a more stable alternative.
A series of ligands based on a calix[4]arene scaffold were developed. Through
modifications to the upper rim of the calix[4]arene scaffold a mono, di, and tri substituted catechol calix[4]arene were designed. After the mono-catechol tri-sulfonated calix[4]arene was found to decompose in solution the catechol substituent was determined to be too reactive for use as a contrast agent. An upper rim tetra substituted iminodiacetic acid calix[4]arene was synthesized. Upon addition of the lanthanide a coordination polymer was likely forming. Using a dye displacement assay it was found that this ligand was not able to out-compete the dye for metal chelation and would not be suitable for MR use. Using established Suzuki chemistry, DO3A functionality was incorporated onto a tri-sulfonated calix[4]arene scaffold. Using a dye displacement assay it was found that the stability constant KML of this complex was similar to DO3A at pH 8.35. At pH 3.99 it was found that no displacement occurred, most likely due to intramolecular hydrogen bonding. / Graduate / 0488 / kjallen@uvic.ca
| Identifer | oai:union.ndltd.org:uvic.ca/oai:dspace.library.uvic.ca:1828/5448 |
| Date | 08 July 2014 |
| Creators | Allen, Kevin John Harvey |
| Contributors | Berg, David Jay, Hof, Fraser Alan |
| Source Sets | University of Victoria |
| Language | English, English |
| Detected Language | English |
| Type | Thesis |
| Rights | Available to the World Wide Web, http://creativecommons.org/licenses/by-nc/2.5/ca/ |
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