Undergraduate Research

Diana Tymochko '25

OUR Featured Researcher: Diana Tymochko '25


Photo Credit: Jacob Strauss
Photo Credit: Jacob Strauss

Diana Tymochko (she/her) is a Biochemistry major conducting mentored research under Professor Manish Mehta. Her project is titled "An investigation of structures of two cocrystals of piracetam using 13C solid-state NMR". 

Please describe your project: 

Within this project, we are investigating pharmaceutical cocrystals, which are crystals composed of an active pharmaceutical ingredient (API/ drug) and a “coformer” (filler/ counter-molecule). Cocrystals are used in pharmaceutics to modify properties of drugs, such as solubility and bioavailability. My project investigates the structure of two cocrystals of piracetam (API mimic and nootropic drug) with two diacid coformers (L-Tartaric acid, p-Hydroxybenzoic acid). When investigating the structure of these cocrystals, we are not only concerned with the nuclear coordinates that can be obtained using high-resolution X-ray diffraction and Neutron Diffraction, but also the electronic structure. We are using magic angle spinning (MAS) and single crystal NMR to evaluate isotropic chemical shifts and chemical shift anisotropy tensors along with their orientation in the crystal frame. Studying the chemical behavior and structure of these cocrystals can help us gain knowledge that can be applied to APIs.

A brief summary (the elevator speech) of your research project:

My research project is concerned with studying structure of two cocrystals of piracetam (mimic of active pharmaceutical ingredient (API) and nootropic drug) with two diacid coformers. By structure I mean not only the nuclear skeleton, but also the surrounding electron distribution. We can obtain information about nuclear skeleton using X-ray diffraction, and about electronic structure using NMR. Knowing the structure of these cocrystals in such detail can help us gain knowledge that can be applied to APIs/ drugs.

Why is your research important?

Cocrystals are important because of their ability to modify the properties of active pharmaceutical ingredients (APIs), such as solubility and bioavailability. This is extremely relevant in the pharma sector where fewer than 1% of candidate drugs eventually reach the market because of their poor biopharmaceutical characteristics, such as poor solubility and amorphicity, rather than toxicity or inefficacy.

What does the process of doing your research look like?

At first, I have to make my cocrystals, which involves mixing two powdered compounds (piracetam and diacid) and ball milling them, basically grinding them in a fancy machine. In order to verify that the correct cocrystal was made, I use Powder X-ray Diffraction, which is a characterization technique that produces a pattern that serves like a fingerprint for each compound. After I have verified that the correct cocrystal has been made, I can finally use the main characterization technique – solid-state NMR, which requires me to pack my cocrystal sample into a tiny rotor (1.6mm or 4mm in diameter), and then spin it at around 30kHz or 5kHz in a probe that is inserted into a very powerful (600MHz) magnet. Rotors spinning 30000 times per second still blows my mind. Recently, I have started growing crystals using slow evaporation, I dissolve my compounds in the solvent and then wait for it to evaporate.

In what ways have you showcased your research?

Thus far, I have only done an informal presentation for student-researchers in chemistry and biochemistry department during summer research. 

How did you get involved in research?

This might be a funny answer, but I have always loved detective mysteries, which might explain my fascination with research and trouble shooting. When I see something “weird” happen, I want to be able to investigate it and explain it. I also love learning and want my knowledge to serve value to some larger vision – potentially developing new pharmaceuticals. So naturally, I wanted to try doing research in college to figure out whether I will enjoy it as much as I thought, and to gain important lab skills that can help me in the future even if I end up working in some different field.

What is your favorite aspect of the research process?   

Seeing something “funny” happen and figuring out why it happens and how to fix it. I had one cocrystal that I have been trying to make so many times, and each time it was turning out different with different Powder X-Ray Patter, which essentially means that new cocrystal was forming each time, even though I seemed to be doing everything the same. I liked the process of tweaking little detail in the procedure to figure out what can lead to the formation of the correct cocrystal.

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

I had no wet lab research experience before starting my project. In teaching labs, we conduct most of the experiments following a rigid protocol, and often already know the right answer, while in research a lot of the time we are just trying different things and see whether something interesting will happen, like choosing different solvents and see how it would affect the crystal growth and quality. In the time that I have worked on this project, I became more confident in making decisions in the lab after having to fix a lot of different problems that often come up, my mentor taught me how to use solid-state NMR, so we have been able to collect high-quality slow and fast-spinning NMR spectra of cocrystals of piracetam that I am studying. I am now trying to grow high-quality single crystals that I can use for doing single-crystal NMR.

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

I think when starting a research project there is always a huge learning curve. I have never learned or done anything I am doing right now before I started research, so I definitely gained so many new lab skills starting with basic safety and ending with super unique solid-state NMR.

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

Don’t hesitate to reach out to professors or students in the labs to ask about research. Don’t be scared of not understanding what is happening in the lab, there is always a learning curve, and things will get clearer the more you do them.