Methods for Fast NMR

Although increasing sensitivity can drastically reduce NMR acquisition time, new methods have evolved that can have a major impact on acquisition and structure determination. Three areas will be briefly presented here that offer reduction in acquisition time, either directly by reducing the time that a sample remains in the NMR or indirectly through processing. 

Other strategies that show great promise in reducing NMR acquisition time utilise methods to obtain multiple sets of data from one experiment through a concept known as time-shared evolution. An example of this process that should find utility in natural products elucidation was demonstrated by a pulse sequence called CN-HMBC.93 Traditionally, a separate 13C-HMBC and 15N-HMBC were acquired independently. However, the CN-HMBC allows both 13C- and 15N-HMBC spectra to be obtained simultaneously. By acquiring both data sets simultaneously, an effective 50% time reduction can be achieved.93 This approach has also been demonstrated for a sensitivity-enhanced 2D HSQC-TOCSY (heteronuclear multiple bond correlation total correlation spectroscopy) and HSQMBC (heteronuclear single quantum 

Parallel acquisition NMR spectroscopy (PANSY) has emerged as a method to provide great time savings for NMR data acquisition and structure elucidation.95 In contrast to the concept of time-sharing evolution, PANSY experiments use a separate receiver for each nucleus. As a proof of concept, Kupce and co-workers demonstrated the potential of PANSY by simultaneously acquiring correlation and correlation spectra, both 

A third area of development that has affected the speed of obtaining molecular connectivity information from NMR takes advantage of the information inherently present in two separate experiments. Traditionally, an analyst would use the information from a group of separate experiments to draw conclusions about molecular connectivity. In recent years, the projection-reconstruction technique97,98 and indirect covariance NMR99 have allowed information from two separately acquired experiments to be correlated into an additional experiment. Both techniques can increase the dimensionality of NMR data providing information that would otherwise require time-consuming acquisitions. 

The projection-reconstruction approach is a technique unrelated to covariance processing which can provide data typically inaccessible to the natural product chemist. For example, 13C-15N correlation spectra were obtained for vitamin B12 at natural abundance.104 Compared with a conventional three-dimensional 13C-15N correlation experiment, the projection-reconstruction method provides a sensitivity enhancement of two orders of magnitude. The final 13C-15N spectrum was reconstructed from data obtained from ll l5N and H- C correlations acquired using a time-shared evolution pulse sequence that allowed all the information to be obtained in one experiment.104 Martin and co-workers also demonstrated the ability to generate 13C-15N correlation spectra using unsymmetrical indirect covariance NMR with vinblastine as an example.105 In the latter case, 13C-15N correlation spectra were obtained from - C HSQC data and H-1sN HMBC data that were acquired separately. Both methods provide access to correlations that would be inaccessible for most natural products at natural abundance. 

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