Benchtop/cryofree NMR

Abstract

Making NMR spectroscopy accessible to a broad scientific community is an ongoing and exciting challenge as this analytical tool plays a central role in many fields of (bio)chemistry. With this in mind, benchtop NMR has enjoyed great success over the last 10 years, whether in academic research, industry, or even educational activities, offering the possibility of using this powerful spectroscopy in situations where high-field NMR is not feasible for economic or practical reasons. Furthermore, the lack of cryogenic fluids in benchtop NMR systems is becoming increasingly important in the current context as the scarcity and unstable pricing of liquid helium are significant concerns for many NMR platforms. This further requires no cryogenic maintenance, skipping routine, and safety concerns when working with cryogenic liquids. It is worth mentioning that the concept of “cryogen-free NMR” is not today limited to low-field permanent magnets, since a new type of cryogen-free power-driven high-temperature-superconducting (HTS) magnet has been recently proposed, which can operate until 9.4 T.

Current permanent magnets deliver fields of 1–2 T (or even 2.4 T for the most recent systems). While such magnetic fields are reminiscent of the early days of NMR in the mid-20th century, their impressive homogeneity results in narrow line widths (less than 0.5 Hz at half-height), making it possible to go beyond the analysis of highly concentrated small molecules. Furthermore, benchtop NMR has benefited from the most recent methodological developments originally proposed for high-field spectrometers, whether in the design of pulse sequences, signal processing, or data analysis based on algorithms. In particular, the implementation of gradient coils in recent benchtop devices has enabled the use of modern NMR experiments that rely on spatial encoding and diffusion contrast, as well as the application of solvent suppression schemes that are effective on both stationary and flowing samples. These improvements have paved the way for various reaction monitoring on-the-fly in standard reactors or within flow-chemistry platforms, along with quality control applications in different fields. As a result, benchtop NMR is becoming a valuable complement to high-field NMR, especially in environments where the latter is not accessible.

This special issue, entitled “Benchtop/cryofree NMR,” includes 19 research articles, one educational paper, and, finally, a mini-review exploring the analytical performance of an HTS magnet operating at moderate fields (9.4 T). This issue focuses mainly on NMR spectroscopy (i.e., FT-NMR), with method developments for the analysis of complex mixtures, solvent suppression, and diffusion measurement, while instrumental considerations for sample temperature control are also presented and discussed. The herein articles also present a wide range of applications in reaction monitoring and quality control in different matrices (pharmaceutical, food, environmental or biological samples) highlighting the versatility of this emerging analytical tool. These contributions are well balanced between academia and industry, offering readers a comprehensive view of current developments and applications in the field of benchtop/cryofree NMR.

We would like to thank Drs. Roberto R. Gil and Gary Martin (MRC Co-Editors-in-Chief) for giving us the opportunity to guest edit this special issue. We also warmly thank David Rovnyak for his strong support, cooperation, and enthusiasm. We are finally grateful to all of the researchers who kindly agreed to contribute because without them, this special issue would not have been possible. Finally, our thoughts are with Michael Maiwald, an outstanding researcher and contributor in the field of low-field NMR, who sadly passed away during the writing of this special issue.