Title of Research Project
Towards the Development of Redox-Responsive Eu(III) Complexes for Cancer Imaging
Major
Chemistry
Research Abstract
Cancer cells display redox dysregulation and lowered cytosolic pH as a means to maintain their over-proliferation. The development of an approach to probe tissue redox state could potentially allow discrimination between healthy and cancerous tissues. Magnetic Resonance Imaging (MRI) is a non-invasive technique used in the diagnosis of a variety of pathologies. The high spatial resolution and its use of non-ionizing radiation make MRI an attractive technique for cancer screening and detection. The quality of an MR image can be further enhanced with the aid of contrast agents, the majority of which are Gd(III) complexes. Gd(III) complexes provide positive contrast via a T1 mechanism. Recent advancements in the development of new MRI contrast agents have drawn attention to the Eu(II)/Eu(III) redox couple. The Eu(II) ion, which is isoelectronic with Gd(III), exhibits similar T1- MRI properties, while the Eu(III) ion displays PARACEST MRI properties. These differences in MRI properties can be exploited to design a redox-responsive MRI contrast agent. Such a probe could potentially allow the non-invasive detection of redox dysregulation in vivo. The goal of this project is to develop a series of Eu(III) imaging agents and investigate the effect of ligand identity on their redox properties. So far, four Eu(III) complexes of glycine-, lysine-, aspartate- and tyrosine-based ligands have been synthesized and characterized by 1H NMR. Cyclic voltammetry was used to evaluate the redox properties of these metal complexes between pH 5.5 – 8.5. Preliminary results show that of the four Eu(III) complexes investigated, the aspartate-based complex displays the most significant pH-dependent redox properties, with a 250 mV change in redox potential over the pH range studied. Future work will involve further investigation of the redox potentials of these complexes over a broader pH range.
Faculty Mentor/Advisor
Osasere Evbuomwan
Included in
Towards the Development of Redox-Responsive Eu(III) Complexes for Cancer Imaging
Cancer cells display redox dysregulation and lowered cytosolic pH as a means to maintain their over-proliferation. The development of an approach to probe tissue redox state could potentially allow discrimination between healthy and cancerous tissues. Magnetic Resonance Imaging (MRI) is a non-invasive technique used in the diagnosis of a variety of pathologies. The high spatial resolution and its use of non-ionizing radiation make MRI an attractive technique for cancer screening and detection. The quality of an MR image can be further enhanced with the aid of contrast agents, the majority of which are Gd(III) complexes. Gd(III) complexes provide positive contrast via a T1 mechanism. Recent advancements in the development of new MRI contrast agents have drawn attention to the Eu(II)/Eu(III) redox couple. The Eu(II) ion, which is isoelectronic with Gd(III), exhibits similar T1- MRI properties, while the Eu(III) ion displays PARACEST MRI properties. These differences in MRI properties can be exploited to design a redox-responsive MRI contrast agent. Such a probe could potentially allow the non-invasive detection of redox dysregulation in vivo. The goal of this project is to develop a series of Eu(III) imaging agents and investigate the effect of ligand identity on their redox properties. So far, four Eu(III) complexes of glycine-, lysine-, aspartate- and tyrosine-based ligands have been synthesized and characterized by 1H NMR. Cyclic voltammetry was used to evaluate the redox properties of these metal complexes between pH 5.5 – 8.5. Preliminary results show that of the four Eu(III) complexes investigated, the aspartate-based complex displays the most significant pH-dependent redox properties, with a 250 mV change in redox potential over the pH range studied. Future work will involve further investigation of the redox potentials of these complexes over a broader pH range.
