Iron(II)/Iron(III) and Cobalt(II) Complexes as Redox-tunable Probes for Magnetic Resonance Imaging (MRI)

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Inflammation is a characteristic feature of many diseases including arteriosclerosis, multiple sclerosis, and cancer. The development of probes to track inflammation could provide information towards the diagnosis and treatment of these diseases. Magnetic resonance imaging (MRI) provides high resolution and deep tissue images, which in conjunction with MRI probes, may enable mapping of inflammation in disease states. In this project, Dr. Morrow is developing new MRI probes that demonstrate a change in signal in the presence of certain molecules that are produced by the immune defense system of the body during inflammation. These MRI probes contain cobalt or iron switches that are part of small molecules or lipid nanoparticles. This project involves the preparation of several new cobalt or iron containing molecules and their study in solution and in animal models of inflammation. Dr. Morrow of the University at Buffalo, the State University of New York is actively engaged in outreach activities that build upon her research to promote engagement of students in science, technology, engineering and mathematics (STEM) disciplines. These activities, which include summer research internships for middle school and high school teachers in Dr. Morrow’s laboratory, are directed at improving education of K-12 students and encouraging their interest in STEM careers. With funding from the Chemical Structure, Dynamics and Mechanisms-B program of the Chemistry Division, Dr. Morrow of the University at Buffalo, the State University of New York is developing transition metal complexes as MRI contrast agents that respond to cellular redox imbalances attributed to inflammation. Inflammation that is associated with the defensive immune response is a characteristic of many diseases and injuries including arteriosclerosis, multiple sclerosis, and cancer. For example, atherosclerotic lesions contain high levels of perioxidase activity. Dr. Morrow is synthesizing new Co(II) and Fe(II)/Fe(III) complexes as MRI contrast agents that are responsive to inflammation. Small molecule coordination complexes of Fe(II) are activated under these oxidizing conditions through the formation of high spin Fe(III) complexes that are relaxivity contrast agents. Liposome systems loaded with Co(II) or Fe(II) show a shift in the position of the signal upon change in redox environment. MRI studies are carried out both in solution and in mice. Dr. Morrow is actively engaged in STEM outreach programs focused on summer research experiences and collaborative projects for middle and high school teachers and for undergraduates to improve education in the STEM fields, in support of broader impacts of the project.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.