Effect of Ligand Side-chain Identity on the Electrochemical Properties of Eu(III) Complexes

The reduction/oxidation (redox) potential of tissue is strictly monitored by electron transfer agents and redox couples to maintain normal physiological processes. However, diseased tissue and cancerous cells disrupt this equilibrium towards more negative potentials. The development of biomedical imaging techniques that allow for non-invasive mapping of tissue redox potentials would enable the detection and diagnosis of diseased tissue. Magnetic resonance imaging (MRI) is a biomedical imaging technique that is non-invasive, and produces three-dimensional images of soft tissue with high spatial resolution. MR images can be further enhanced by contrast agents (CAs), most of which are Gd(III) complexes, that provide contrast by a T1 mechanism. However, Gd(III) complexes suffer from a few drawbacks that limit their application as responsive imaging agents. Eu(III) complexes have been widely studied as responsive paramagnetic chemical exchange saturation transfer (PARACEST) MRI agents, while Eu(II) complexes have been found to exhibit T1 MRI properties due to their electronic similarities with Gd(III). Thus, the Eu(II)/Eu(III) redox couple can be taken advantage of in the design of redox-responsive MRI contrast agents. The goal of this project is to acquire a better understanding of the impact of ligand side-chain identity on the redox potential of the Eu(II)/Eu(III) couple. To date, Eu(III) complexes consisting of four acetamide-, glycinate-, and aspartate side-chains were altered by substituting one of the four side-chains with a pyridine or quinoline moiety. The resulting complexes were analyzed by cyclic voltammetry at pH 7.5. The results obtained so far showed that on average, the redox potentials of each complex registered a +67mV and +176 mV shift upon replacement of one side-arm with a pyridine and quinoline, respectively. These results were consistent for all complexes regardless of whether the other side-chains were acetamides, glycinates, or aspartates, and suggest that “softer” donor atoms that are part of highly conjugated systems are better at stabilizing the Eu(II) oxidation state upon reduction of the Eu(III) complex