Access Type

Open Access Dissertation

Date of Award

January 2016

Degree Type


Degree Name




First Advisor

Matthew J. Allen


The research projects described in this dissertation are focused on studying the oxidation of EuII-containing complexes within the context of responsive MRI. Prior to this research, EuII had not been explored within the context of oxidation-responsive MRI nor had the use of this ion been reported in vivo. The results of these studies enable predictions about the oxidation-responsive behavior of EuII-containing complexes in vitro and in vivo.

The EuII-containing cryptate 1.33 was used to evaluate EuII-based positive contrast enhancement after intravenous, intraperitoneal, and subcutaneous injections. The transitory behavior of the positive contrast enhancement correlated with reported levels of oxygenation and rates of diffusion. Additionally, europium was observed to clear primarily through the liver and kidneys with no observable adverse side effects.

The EuII-containing cryptate 3.6 was synthesized and characterized in the solid and solution phases. While a chloride counterion was coordinated in the solid state, conductivity and 17O-NMR experiments strongly suggested chloride counterions were dissociated in aqueous solution. EuII-based positive contrast enhancement persisted in a mammary carcinoma model for at least 3 hours after intratumoral injection. Additionally, EuII-based positive contrast enhancement persisted specifically in necrotic regions of the tumor as evidenced by histological staining.

The EuII-containing complex 1.33 was encapsulated inside of liposomes with an average diameter of 110 nm. Positive contrast enhancement and CEST were observed before oxidation of 1.33, but only CEST was observed after oxidation of 1.33 by molecular oxygen in the air. CEST effect was likely caused by the exchange of hydroxyl protons on cholesterol or water molecules associated with the outer phospholipid bilayer. This project demonstrated the feasibility of encapsulating air-sensitive EuII-containing complexes in liposomes and the ability to combine positive contrast enhancement with CEST.

The commercially available EuIII-containing complex 5.1 was reduced with Zn dust to produce its EuII-containing analogue 5.2. Changes in oxidation state were monitored using luminescence, EPR, UV–visible, and 1H-NMR spectroscopies. Collectively, all of the experiments indicated that europium remained chelated upon reduction to the +2 oxidation state and oxidation back to the +3 oxidation state. While the poly(amino glycinate) ligand caused the EuII/III redox couple to approximately –0.9 V vs Ag/AgCl, the kinetic stability of the complex in the +2 oxidation state was within the range of clinically approved contrast agents. Only positive contrast enhancement was observed when EuII was present, and only CEST was observed when EuIII was present.

The ability to essentially disable positive contrast enhancement through the oxidation of EuII holds great potential for responsive MRI. The balance of oxidative and kinetic stability will yield fundamental information regarding the EuII/III redox couple and coordination environment.