NMR at very high fields.

One obvious disadvantage is cost. Commercial 750 MHz instruments are currently being quoted at prices around £2 000 000 while a 500 MHz spectrometer costs around £500 000. A special room with a high ceiling (4.5 m) and, possibly, some stray field protection is also required. These financial implications mean that a 750 MHz instrument is perhaps more likely to form part of a national facility. As mentioned above, another possible disadvantage is the field-dependence of some NMR relaxation properties; protein 1 H resonances do not seem to broaden much with increasing field but the time taken for thermal equilibrium to be re-established after a radiofrequency pulse (longitudinal relaxation) increases. A third potential disadvantage is associated with the fields applied in addition to the main static magnetic field. Modern heteronuclear NMR experiments on macromolecules are very sophisticated and numerous radiofrequency pulses [[5]xExperimental NMR techniques for studies of biopolymers. Bax, A. Curr. Opin. Struct. Biol. 1991; 1: 1030–1035Crossref | Scopus (8)See all References, [8]xAmino-acid type determination in the sequential assignment procedure of uniformly 13 C / 15 N-enriched proteins. Grzesiek, S. and Bax, A. J. Biomolec. NMR. 1993; 3: 185–204PubMedSee all References] and field gradients [9xGradient enhanced spectroscopy. Hurd, R.E. J. Magn. Reson. 1990; 87: 422–428See all References][9] are used to select appropriate NMR signals. The demands on these various additional fields become greater with increasing static field strength. The radiofrequency fields, for example, can become inadequate to cover the entire spectrum of interest uniformly and the increased strength required to cover the spectral range can cause significant heating of the sample.In spite of the potential problems, we believe that the advantages of very high fields are significant. It is clear that 1994 will see the installation and operation of several 750 MHz NMR spectrometers world-wide. Even higher field strengths will soon become technically feasible and magnet manufacturers expect to be able to produce magnetic fields equivalent to proton frequencies of 900 MHz within the next five years. It also seems likely that other aspects of NMR spectrometer technology, such as the development of new sophisticated heteronuclear pulse sequences [5xExperimental NMR techniques for studies of biopolymers. Bax, A. Curr. Opin. Struct. Biol. 1991; 1: 1030–1035Crossref | Scopus (8)See all References][5] will continue to advance. These technical innovations together with the ‘brute force’ application of very high fields will continue. It thus seems likely that the astonishing ability of modern NMR to explore the structure and dynamic properties of proteins in solution will carry on being extended. This will be seen by many to justify the high financial cost of the new very high field instruments.