Reviews & Book Chapters

The Role of Pulsed-field Gradients in Modern NMR Pulse Sequence Design

Pulsed-field gradients (PFGs) play an important role in the development and understanding of modern NMR methods. With the ultimate goal of constructing robust pulse sequences that create high-quality NMR spectra with minimum set-up, PFGs are utilized to achieve an exclusive selection of a specific coherence transfer pathway as well as to purge all kinds of undesired magnetization. PFGs reduce the number of needed phase cycle steps to a bare minimum, allowing for accelerated NMR data acquisition in shorter spectrometer times. The potential and diversity of several PFG-based NMR elements are presented, as well as instances of their implementation in time-efficient NMR solutions. Practical aspects such as NMR data collection needs and the attainment of pure in-phase absorption lineshapes are discussed for the most useful NMR experiments.

NMR Spectroscopy, Applications, Small Molecule Structuring Strategies

Nuclear magnetic resonance (NMR) spectroscopy is a powerful tool for the efficient elucidation and validation of constitution, conformation and configuration of small and medium-sized molecules in solution. A basic description of fundamental NMR experiments regarding chemical structure is provided. Although spectral NMR data analysis and interpretation are performed manually, the combination of computer-assisted structure elucidation (CASE) expert systems and density functional theory (DFT) calculations are increasingly used for structure verification. The important role of anisotropic NMR parameters (residual dipolar couplings (RDCs) and residual chemical shift anisotropy (RCSA)) determined in weakly aligned media is also discussed for the automated determination of the relative configuration in complex molecular systems having multiple chiral centers. Finally, some modern NMR concepts incorporated in current pulse sequence developments are briefly described. 

Chapter 6: Current Pulse Sequence Developments in Small-molecule Nuclear Magnetic Resonance Spectroscopy  

 The current developments in the design and the application of modern nuclear magnetic resonance (NMR) pulse sequences in small molecules are overviewed. The concepts of fast NMR, pure-shift NMR, perfect NMR and ultra-long-range correlation NMR are described and illustrated with examples.

Recent Advances in Small Molecule NMR: Improved HSQC and HSQMBC Experiments

A general description of the latest developments in HSQC and HSQMBC experiments designed for small molecules at the natural isotopic abundance is reported. A discussion is made on the details introduced into novel NMR pulse sequences with special emphasis on modern concepts such as fast NMR or pure-shift NMR and also on robust techniques affording pure in-phase multiplet patterns, which are amenable for a simpler and a more accurate analysis. The suitability of some of these methods for the quantitative measurement of one-bond and long-range proton–carbon coupling values in molecules in isotropic and weakly aligned anisotropic conditions is also reviewed. 

Time-Shared NMR Experiments

Details on the implementation of the simultaneous evolution of multiple frequencies into the same time period of a NMR pulse sequence are introduced. Timeshared (TS) versions of the most useful inverse 2D NMR experiments (TS-HMBC, TS-HSQC, TS-HSQC-TOCSY, and TS-HSQMBC) are presented and illustrated for simultaneous acquisition of 1H/13C and 1H/15N NMR spectra. The major benefits associated to the parallel acquisition of multiple spectra from a single NMR experiment are spectrometer time savings and the achievement of multiple and complementary information with improved sensitivity gains per time unit.

Solution-State NMR Experiments based on heteronuclear cross-polarization

Heteronuclear coherence transfer in liquid-state NMR applications has been traditionally performed using pulse-interrupted delay schemes such as INEPT-type pulse trains. So far, the alternative use of heteronuclear crosspolarization (HCP) has only been limited to a few cases involving exclusively in-phase to in-phase transfers. In this revision work a theoretical description on the effect and the characteristic anisotropic features of HCP is introduced in terms of product operator formalism. A very intuitive and simple graphical black-box approach based on a pictorial nonclassical vector representation that only consider the available input/output magnetization is also presented to understand the general transformations that are undergoing under such rather complex HCP processes. The appropriate manipulation of magnetization components during the HCP block offers novel concepts in pulse sequence design. In this way, new liquid- state multidimensional NMR methods incorporating HCP-driven processes have recently been developed and successfully applied for both small-to-medium-sized molecules and large labeled bio-molecules, as will be discussed in this review.