By Tyler Irving
Posted March 2011
Imagine trying to put together a puzzle when a quarter of its pieces are invisible. That has more or less been the situation faced by chemists using nuclear magnetic resonance (NMR) spectroscopy to study large proteins. The technique easily detects three of the four basic building blocks of life: hydrogen, carbon and nitrogen. The fourth, oxygen, had remained elusive until a team led by Gang Wu, professor of chemistry at Queen’s University, tackled the problem.
When exposed to a strong magnetic field, the atomic nuclei of elements with odd numbers of either protons or neutrons give off energy in the form of radio waves. In the case of oxygen, however, the only stable odd-numbered isotope (17O) has a nuclear spin that is quadropolar, rather than dipolar, as is the case for 1H, 13C, and 15N.This makes the signal extremely hard to detect. Wu’s team used three methods to crank up the volume. First they attached small molecules enriched with 17O to the larger protein. Then, they tweaked their radio receivers to be more sensitive to the isotope’s characteristic signal. Finally, they brought their protein to the National Ultrahigh-Field NMR Facility for solids in Ottawa, in order to expose it to a magnetic field 500,000 times stronger than that of the earth.
The technique works well enough in the solid state, but surprisingly, it works even better when the protein of interest is in solution. That’s because the large proteins that slowly tumble in solution actually give a sharper NMR signal than fast-moving ones. This fortuitous fact means that the technique can be used in real time. “Because this now works in solution, we can use this to monitor chemical reactions,” says Wu. “We’re hoping to be able to detect reaction intermediates, especially enzymatic reaction intermediates.””
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