Discipline: Chemistry and Chemical Sciences
Subcategory: Chemistry (not Biochemistry)
Jamonica L. Moore - Auburn University
Co-Author(s): Dean D. Schwartz, Auburn University, Auburn, AL; Christian R. Goldsmith, Auburn University, Auburn, AL
Superoxide dismutases (SODs) are metalloenzymes that catalyze the degradation of the reactive oxygen species (ROS) superoxide (O2-) to hydrogen peroxide (H2O2) and dioxygen (O2). Excessive production of ROS is correlated with oxidative stress which is a marker of cardiovascular, neurological, and inflammatory diseases. Due to the correlation between ROS and these diseases, there is a significant interest in developing a strategy to control their in vivo concentrations. One therapeutic strategy would be to administer a pharmaceutical that would convert the ROS to a more innocuous molecule, such as oxygen (O2) or water (H2O). A small molecule that resembles the enzymes responsible for the natural alleviation of oxidative stress could potentially catalytically degrade one or more types of ROS. Here we describe the design and synthesis of highly active catalysts for the degradation of O2-. Using a previously published synthetic method, our lab prepared coordination complexes with polydentate ligands that contain redox-active quinol groups and innocuous metal ions Zn (II) and Ga (III). The complexes were structurally characterized by 1H and 13C Nuclear Magnetic Resonance (NMR), elemental analysis, Mass Spectrometry (MS), and solid-state crystallography. After determining the composition of the complexes, their antioxidant properties were assessed for potential SOD mimicry via the xanthine oxidase/hypoxanthine/lucigenin and the 2,2-diphenyl-1-picrylhydrazyl (DPPH) assays. The measure of antioxidant activity was used a preliminary determination of SOD mimicry. Preliminary measurements indicate complexes with innocuous metal ions are indeed functional SOD mimics. However, further analysis is necessary to fully characterize SOD activity. One method is to use stopped-flow kinetics to study the direct reactions between the coordination complexes and O2-. Based on the preliminary data, we find that the SOD activity scales with the positive charge on the metal complex and that activity is lost if the ligand dissociates from the metal center. Future research involves synthesizing macrocycle ligands with redox-active quinol groups. The use of a macrocycle could increase the stability of complexes and allow for one or more additional accessible sites on the metal ion for O2- coordination.
Funder Acknowledgement(s): The authors thank Ms. Cristine Camp for technical assistance. We thank Auburn University and the National Science Foundation (NSF-CHE-1662875) for financial support.
Faculty Advisor: Christian R. Goldsmith, firstname.lastname@example.org
Role: I synthesized and characterized the Zn (II) and Ga (III) complexes.