Computational Elucidation of the Synthesis Mechanism of a Novel Asymmetrical Piperidone

Project Title

Computational Elucidation of the Synthesis Mechanism of a Novel Asymmetrical Piperidone

Faculty Mentor(s)

Project Description

Piperidones are nitrogen-containing heterocycles commonly used in drug development as homologs of biomolecules. Collaborators at the University of Arizona have developed a novel chiral piperidone synthesis through an undetermined chemical mechanism. This project focuses on applying density functional theory calculations using Gaussian modeling software to determine the most likely mechanism of synthesis, with emphasis on finding the lowest-energy transition states and modeling a total reaction coordinate.

 

Why is your research important? 

Nitrogen-containing heterocycles are vital functional groups found in the vast majority of medicines. Piperidones are particularly useful in medicine, especially as precursors to other nitrogen-containing heterocycles. Organic chemists in pharmaceutical development also highly value nonplanar and asymmetrical medicinal compounds, as these properties tend to reduce side effects. The reaction I am studying may uncover a new and potentially lower-energy and lower-cost method of asymmetrical nitrogen heterocycle production.

 

What does the process of doing your research look like? 

I model the reaction in chemical building software and make adjustments to it using a standardized coding process. Over the course of 6 months, I've found about 1,000 versions of the reaction, and from these versions, I can isolate the most likely reaction pathway and provide information about the energy required for it to occur.

 

What knowledge has your research contributed to your field? 

Computational research has been vital to the field of chemistry by providing a framework for the molecular mechanisms that underlie chemical reactions. What I've learned in this particular project will be helpful information for our collaborators because they will know the exact mechanism and energy barriers they are working with as an explanation for their experimental yields.

 

In what ways have you showcased your research thus far? 

I have presented once, about one month into my research, and I didn't have many findings yet; I plan on presenting my research to the chemistry department labs this summer once my full reaction coordinate is completed.

 

How did you get involved in research? What drove you to seek out research experiences in college? 

I've been interested in pursuing an MD-PhD after undergraduate study, and I wanted to explore what drug-related research might be like as early as possible.

 

What is your favorite aspect of the research process? 

I really enjoy the process of discovering something truly new, especially if it might be beneficial to the health of others down the line. 

 

How has working with your mentor impacted the development of your research project? How has it impacted you as a researcher? 

My mentor assigned this project to me because she knows I'm interested in the medical field. She's been invaluable in guiding me through the process of modeling this reaction, and my experiences in meeting with her to discuss this project have inspired confidence in my capabilities as a researcher.

 

How has the research you’ve conducted contributed to your professional or academic development? 

My project has allowed me to have valuable research experience before I pursue it in post-undergraduate study. I've become particularly fond of this specific area of chemistry research because of its flexible schedule, and the amount of coding experience I've gained is particularly useful; I've developed a skillset I otherwise would not have received from traditional chemistry classes and teaching labs.

 

What advice would you give to a younger student wanting to get involved in research in your field? 

If you're interested in research, get in touch with your professors! Make connections with the people you admire and your world will expand.