Pursuing direct 13C detection for biomolecular NMR in solution

Direct detection of 13C-NMR spectra, with or without 1H decoupling, has been used since the early days of NMR for structure elucidation and dynamic studies of relatively small molecules, e.g. synthetic compounds and natural products. However, 13C-NMR was only seldom applied in studies of biological macromolecules due to its much lower intrinsic detection sensitivity compared to 1H-NMR. With the advent of inverse 1H-detected heteronuclear experiments, multidimensional correlation techniques have contributed significantly to the success of biomolecular NMR. In recent years two major technological advances, the availability of increasingly higher magnetic fields and the development of cryogenically-cooled probeheads, have brought the sensitivity of NMR spectroscopy into realms that were unforeseeable less than a decade ago. Consequently, 13C sensitivity has increased by an order of magnitude, allowing the routine use of 13C-detected experiments on isotopically enriched samples for biomolecular NMR applications. Examples of applications are here illustrated.