Discipline: Chemistry and Chemical Sciences
Subcategory: Chemistry (not Biochemistry)
Session: 3
Room: Exhibit Hall A
Jaden Webb - Missouri State University
Co-Author(s): Matthew R. Siebert, Missouri State University, Springfield, MO
Nature provides many lessons on the biological impacts of chemical agents. Rotenone, a naturally occurring substance in the rotenoid family, was once used as a pesticide and piscicide. Its use was banned in the US due to an alarming realization: geographical areas where rotenone was used showed an increased rate of Parkinson’s disease. The cause of Parkinson’s is not yet understood but understanding how Nature produces rotenone may help lead us toward an answer. Rotenone is naturally synthesized (called biosynthesis) in plants from the amino acid L-phenylalanine. There is some controversy as to whether this first step (conversion of L-phenylalanine to trans-cinnamic acid) proceeds via an E1cb, E1, or E2 elimination pathway. We (among others) hypothesize that L-phenylalanine is converted to trans-cinnamic acid through an E1cb elimination reaction. Utilizing quantum chemical calculations will allow for atomic-level insight into the process by which L-phenylalanine is converted to trans-cinnamic acid. The M06-2X/6-31+G(d,p) method was used to optimize stationary points on the potential energy surface for the aforementioned conversion as well as several other reactions known to proceed via either of E1cb, E1, or E2 elimination pathways. Thus far, most significant structures describing the reaction have been located in the gas-phase as well as in water solvent. These mechanisms of action, elucidated in the absence of an enzyme, provide energy profiles for the intrinsic reactivity involved in the conversion of L-phenylalanine to trans-cinnamic acid. Intrinsically, the E1cb mechanism is still viable. However, we have yet to locate a few critical stationary points. We look forward to the incorporation of the enzyme structure (phenylalanine ammonia lyase) into our simulations and the implications that this work will have on our collective understanding of Parkinson’s disease.
Funder Acknowledgement(s): We gratefully acknowledge the Missouri State University College of Natural and Applied Sciences and Department of Chemistry for their support of this research.
Faculty Advisor: Matthew R. Siebert, MSiebrt@MissouriState.edu
Role: I used computational modeling via Guassian16 to find the lowest energy states for most of the structures involved in each elimination reaction. These were found using optimization frequency analysis.