Ryan McCulla, Ph.D., assistant professor of chemistry at Saint Louis University, has received a $570,000 research CAREER award from the National Science Foundation (NSF). The award is given through the NSF's Chemical Structure, Dynamics and Mechanism Program.
|Ryan McCulla, Ph.D.|
McCulla will explore the reactivity of atomic oxygen with biomolecules and the resulting transient oxidation products. In the upper atmosphere, atomic oxygen is generated when cosmic rays split molecular oxygen into two oxygen atoms. However, there are very few methods of generating atomic oxygen in liquid solution.
Sulfenic acids are often proposed as important intermediates in systems that protect life from reactive oxygen species generated as a natural consequence of aerobic respiration. By characterizing the reactivity of sulfenic acids, this research seeks to understand the critical role sulfenic acids play in maintaining the balance between the necessity of reactive oxygen species to sustain life and their inherent toxicity.
Recently, McCulla's research group developed the first molecules capable of cleanly releasing atomic oxygen in water, which allowed them to begin to probe the reactivity of atomic oxygen with biological molecules such as DNA and peptides. Initial studies indicated that atomic oxygen is a more selective oxidant than other reactive oxygen species. This selectivity, combined with the photochemical release of atomic oxygen, allows the study of reactive intermediates, such as sulfenic acids, that would otherwise be difficult to characterize.
For this study, the chemistry sulfenic acids in physiologically relevant conditions will be investigated by utilizing photoactivatable atomic oxygen precursors and computational methods. Unless specifically stabilized, sulfenic acid cannot be isolated, which makes studying their reactivity challenging.
"Sulfur redox chemistry plays a central role in the regulation of reactive oxygen species, which are believed to contribute to aging, various pathologies, and important biological processes such as cell signaling," McCulla said. "The photoactivatable reagents being developed by my group provide a means to study some fundamental aspects of sulfur redox chemistry that simply cannot be ascertained with other current methods. My hope is by increasing our understanding of sulfur redox chemistry in physiological conditions new therapeutic targets or strategies will be identified and developed."
A complementary educational program that integrates computational chemistry with guided inquiry methods will also be developed. The use of computational methods allows students to rapidly generate data, which allows them to use their creativity while exploring chemical concepts. The effectiveness of this program will be assessed by implementing a short course in local high schools.
In addition to improved understanding of chemical concepts, this program seeks to inspire students to pursue careers in science by exposing them to the role creativity plays in scientific discovery.