NMR research fights breast cancer

Carnegie Mellon associate research professor Roberto Gil has employed nuclear magnetic resonance (NMR) spectroscopy to analyze the chemical structure of a compound known as withanolide, known to inhibit the growth of breast cancer cells.
NMR spectroscopy has been in use for the past decade and has provided new insight on the structure of chemical compounds.
Nuclear magnetic resonance is a property of atomic nuclei, allowing them to absorb electromagnetic radiation and emit the same energy back out.

By using the resonance frequency of the emitted energy and applying quantum physics techniques, researchers can find the type and orientation of the atoms involved. A member of Carnegie Mellon University’s chemistry department, Gil worked on developing residual dipolar couplings (RDC), a new anisotropic parameter for the NMR process. Using this parameter, one can more easily determine the structure of small organic molecules, which are often overlooked by traditional liquid NMR techniques.

“This is a relatively new field for NMR of small molecules that I can call ‘NMR spectroscopy in anisotropic media,’ ” Gil said. The parameters, he continued, include not only RDC, but also residual chemical shift anisotropy (RCSA) and deuterium quadrupolar splitting. Gil applied RDC to jaborosalactol 24 (or withanolide), a steroid molecule in the Jaborosa parviflora plant, and found out how its atoms were arranged. The analysis shows that it may have some use in the future for breast cancer resistance.
Using RDC over NMR had several benefits. According to Gil, while NMR detected three potential structures for the jaborosalactol, RDC narrowed it down to one.

Unlike NMR, RDC reads the magnetic interactions between atomic nuclei, allowing their overall orientation to be determined even at long distances. Although RDC is not a new technology, only after recent findings has it been able to be used on molecules like withanolide. Previously, this technique was only compatible with DNA and protein analysis. The breakthrough came with the development of an elastic polymer gel, which traps small molecules within it and allows them to align.

The gel is known as poly-methyl methacrylat (PMMA) and was a result of Gil’s work in coordination with Carnegie Mellon faculty members Nicolay Tsarevsky and Krzysztof Matyjaszewski. There are several advantages to using PMMA over other available gels. Not only is it comparatively easy to use and cost-friendly, but it also has an easily removable background signal.

Besides Tsarevsky and Matyjaszewski, Gil also collaborated with Viviana E. Nicotra of Argentina and a group from the University of La Laguna in the Canary Islands, Spain. Their research has been submitted to the Journal of Natural Products, reporting the activities of the jaborosalactol 24 with their work on other plant molecules.

In the past, Gil worked in the field of bioactive natural products. “At a certain point I have isolated and reported a natural product that inhibits the aromatase enzyme involved in postmenopausal hormone-dependent breast cancer,” he said.