New Directions for Redox-Active Ligands: Ratiometric Sensors for H2O2 with 19F and 1H MRI Outputs and Functional Mimics of Superoxide Dismutase with Non-Enzymatic Metals

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The overproduction of reactive oxygen species (ROS) has been linked to a wide array of health conditions, including many cardiovascular, neurological, and inflammatory disorders. Currently, it is difficult to assess the concentrations of ROS in vivo. The lack of reliable imaging techniques makes it difficult to understand the roles of ROS in the human body. A pattern of oxidative stress may be used to distinguish disorders that give rise to similar clinically observable symptoms, and the ability to detect ROS overproduction in vivo could potentially diagnose these conditions more quickly and accurately. In this project funded by the Chemical Structure, Dynamics, and Mechanisms-B Program of the Chemistry Division, Dr. Christian R. Goldsmith of Auburn University is developing small molecule sensors for the ROS hydrogen peroxide (H2O2) that gives rise to two distinct magnetic resonance imaging (MRI) signals before and after their reaction with H2O2. By comparing the signals, one may be able to directly assess the concentration of H2O2 in a particular region of the body. Dr. Goldsmith is also interested in observing how antioxidants interact with ROS. Dr. Goldsmith is also engaged in outreach activities that heighten the involvement of undergraduate students in science, technology, engineering, and mathematics (STEM). These activities include giving research talks at local colleges and providing summer research internships in Dr. Goldsmith’s laboratory. These activities are designed to improve both undergraduate science education in the East Alabama area and the diversity of the future STEM workforce.Dr. Christian R. Goldsmith is developing new transition metal complexes that can detect and degrade reactive oxygen species (ROS). The research produces redox-responsive contrast agents for magnetic resonance imaging (MRI) and functional mimics of superoxide dismutase (SOD) enzymes. The new MRI contrast agents are iron complexes with fluorinated redox-active quinol-containing ligands. In their reduced Fe(II)-quinol forms, these give rise to weak H-1 and strong F-19 MRI signals. After oxidation by H2O2, the Fe(III)-para-quinone products display weak F-19 MRI but strong H-1 signals, with the enhancement in H-1 MRI deriving from the increased paramagnetism and higher aquation of the metal center. The contrast agents are therefore bimodal ratiometric sensors for H2O2. The superoxide dismutase (SOD) mimics consist of quinol-containing ligands coordinated to redox-inactive transition metal ions, specifically Zn(II) and Ga(III). These complexes use the quinol/para-quinone redox couple to alternatively reduce and oxidize superoxide and bypass the need for a potentially harmful redox-active transition metal ion. New quinol-containing ligands increase the catalytic activity by enabling superoxide to more readily access the metal center. Given the involvement of ROS in disease, these complexes may lead to improved diagnostic options for several health conditions. The project’s reliance on inorganic chemistry, organic chemistry, and biochemistry teach undergraduate and graduate students a broad array of skills. Dr. Goldsmith’s laboratory are also presenting research seminars at primarily undergraduate institutions in the East Alabama area and enable their students to participate in cutting-edge scientific research by providing two summer internships per year 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.