Preface Free

Nuclear magnetic resonance spectroscopy is arguably one of the most useful analytical methods to look at molecules in solutions. This is in large part thanks to the broad range of NMR experiments that are available, and to the corresponding wealth of chemical and biological information that they can provide. 2D experiments are a very important part of the NMR method landscape, and they provide information that cannot be accessed with 1D NMR alone. To take one example, structure elucidation of molecules in solution relies heavily on the use of 2D NMR experiments that provide essential information on atom connectivity.

2D NMR experiments are classically acquired through multiple repetitions of the same pulse sequence motif, with each of these repetitions starting with the delay for magnetisation to return to or near its equilibrium value. As a result, experiment durations are at least an order of magnitude larger than for 1D experiments, and that puts many important samples and questions out of the reach of classic 2D experiments. This limitation is particularly acute for applications that require high-throughput, and for the analysis of samples that evolve in time. Faced with such limitations, NMR spectroscopists have developed an impressive and very diverse array of complementary methods to accelerate 2D experiments, and these have in turn unlocked important applications in many different fields of science.

This book provides an up-to-date description of fast 2D solution state NMR methods and their applications. It is divided into two parts, where part I contains a description of the most common fast 2D NMR methods, and part II contains accounts of applications in different fields.

Part I of this book starts with the description of the role of pulsed-field gradients, and their use to accelerate NMR experiments by alleviating the need for phase cycling. Several complementary approaches to accelerate 2D methods are then described, based on alternative sampling and signal processing methods (aliasing/folding methods, non-uniform sampling and signal processing for highly resolved 2D NMR), on the reduction of removal of interscan delays (fast-pulsing and multi-FID detected 2D methods), and on spatial parallelisation (ultrafast 2D NMR). The final chapter covers the connected topic of pure-shift NMR. Each of these chapters provides a pedagogical account that should serve as a clear introduction to newcomers in the field, and provides a modern and useful summary to experienced NMR spectroscopists as well.

Part II of this book covers a diverse range of topics, including reaction monitoring, the investigation of dynamic events in biomolecules, industry applications, metabolomics, hyperpolarisation, as well as in vivo spectroscopy, experiments in inhomogeneous fields and oriented media, and the study of microstructures. In each of these cases, the relevance of 2D experiments is explained, and examples of applications of fast methods are described. The complexity of the samples and questions that are addressed in these chapters are a clear indication of the relevance of fast 2D NMR methods to study molecules in solution.

We were initially contacted by the editors of the RSC NMR book series to work on a book on fast NMR methods. We were of course enthusiastic, and we thought that focusing on 2D (and not higher-dimensional) methods would be a way to have a more targeted, original and eventually useful book. While many of the concepts that apply to 2D NMR remain valid and relevant for higher-dimensional experiments, the majority of this book thus concerns developments and applications to small molecules.¹

We are very grateful to all of the contributors to this book, who have kindly agreed to contribute excellent and useful chapters that could reach a broad audience. We are also grateful to the Books team at the Royal Society of Chemistry, and the editors of the NMR book series, for inviting us to edit this book and for all the support. We also wish to acknowledge support from the European Research Council (ERC) under the European Union's Horizon 2020 research and innovation program (grant agreements no. 801774/DINAMIX and 814747/SUMMIT), the Region Pays de la Loire (Connect Talent), the French National Infrastructure for Metabolomics and Fluxomics MetaboHUB-ANR-11-INBS-0010 (www.metabohub.fr) and the Corsaire metabolomics core facility (Biogenouest). We hope that you will enjoy this book and look forward to all the future methods and applications that it helps to envision.

Jean-Nicolas Dumez and Patrick Giraudeau