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SPECTROSCOPY
New technique is orders of magnitude faster than conventional methods S ince the development of multidimensional nuclear magnetic resonance (NMR) spectroscopy some three decades ago, spectroscopists have hoped to obtain multidimensional spectra more rapidly. Now, chemistry professor Lucio Frydman and coworkers at Weizmann Institute of Science, Rehovot, Israel, have devised ultrafast multidimensional NMR, a technique that can shorten by orders of magnitude the time required for multidimensional experiments [Proc. Natl. Acad. Sci. USA, 99, 15858 (2002)].
Ultrafast multidimensional NMR could aid studies of chemical structure and dynamics and could be useful in combinatorial chemistry, where large numbers of compounds need to be analyzed rapidly. It might also make it possible, Frydman says, "to record NMR movies of dynamic systems--such as proteins folding and in vivo metabolism." Multidimensional NMR measures the chemical environments of atomic nuclei--as does one-dimensional NMR--but it also establishes spatial and/or bond correlations among nuclei. And "These gains, however, are achieved at the expense of collecting hundreds or thousands of individual scans, where the timing parameters that define the NMR pulse sequence are systematically incremented," Frydman notes. Therefore, 2-D NMR experiments take minutes or hours, and 3-D procedures take hours or days, whereas a 1-D scan takes just a fraction of a second. Frydman's group has now reduced multidimensional experiments to 1-D duration by acquiring each multidimensional spectrum in a single scan. Magnetic field gradients partition a sample into slices and ascribe to each slice the role individual scans play in a conventional multidimensional experiment. This yields improvements of one to three orders of magnitude in overall acquisition time. "It's an ingenious and conceptually novel idea," says NIH biophysical chemist Ad Bax. "But I suspect that its practical impact may be somewhat limited by its inherently low sensitivity--which appears rather fundamental, as Frydman and coworkers point out in their paper--and by technical limitations on what resolution one can obtain in practice--which is not a fundamental problem, but a limitation of today's hardware. There are lots of cases where one has 'sensitivity to burn,' and that's where I expect the technique is going to be particularly useful, but it probably will not help out in cases where signal-to-noise is a limiting factor--as is commonly the case in protein NMR." |
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