With support from the Chemical Structure, Dynamics and Mechanisms-B Program, Professor Ryan McCulla of Saint Louis University investigates the chemical pathways for biological oxidation. Highly reactive atomic oxygen is formed from certain ring-containing molecules when they are exposed to ultraviolet or visible light. This reaction - known as photochemical cleavage - can be carefully directed so that the atomic oxygen is formed in very specific places within biological cell membranes. Once the atomic oxygen is formed and released, it can attack carbon-carbon double bonds in other biomolecules. Knowing more about how and when light can be used to generate atomic oxygen and how this oxygen attacks other molecules (in a process called oxidative stress) may enable scientists to develop new disease therapies that are initiated by light instead of other chemicals. Oxidative stress has been associated with cardiovascular disease, diabetes, and smoking cigarettes. This research facilitates the investigation of the physiological effects on the cell membranes arising from oxidative stress. In the long term, this work may have beneficial impacts on the health and well-being of society. In addition to helping to develop fundamental science, Professor McCulla encourages the full participation of underrepresented minorities in science. As part of this project, high school students from the Jennings School District and/or the St. Louis Public School District are involved in an intensive summer research experience. Additionally, over 300 middle school and high school students from the Jennings School District are encouraged to pursue their interest in a STEM career during the Jennings Science and Technology Day activities.
Alkenes are rapidly oxidized by atomic oxygen. The overall objective of this research is to reveal how the process of photo-deoxygenation, alkene structure, and local environment influence the mechanism of oxidation and the distribution of oxidized products. To determine if the initial oxidation step occurs through a charge transfer or radical pathway, cyclopropylcarbinyl probes, transient absorption spectroscopy, kinetic isotope effects, and computational methods are used. Determining the nature of the initial step is crucial to understanding how conditions influence the observed lipid oxidation products. The products observed for lipids within a membrane are also expected to be sensitive to the site of atomic oxygen release. To probe this hypothesis, atomic oxygen precursors that are expected to specifically release atomic oxygen within the interior or exterior of the lipid bilayer are prepared and their lipid oxidation profiles are determined. While atomic oxygen is photo-released by a number of heterocyclic oxides, photo-deoxygenation has been observed to generate oxidized products not associated with atomic oxygen. Characterizing this mechanism and the associated alkene oxidation products expands the potential applications of photo-deoxygenation. The mechanistic detail obtained from these studies lays a foundation for understanding how lipid oxidation by photo-deoxygenation affects cellular processes. The fundamental knowledge could be used to improve phototherapies.
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.
