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The combination of ex situ dynamic nuclear polarization (DNP) with nuclear magnetic resonance (NMR) leads to signal-to-noise enhancements of 10(3)-10(4) compared to conventional NMR. Ex situ DNP, however, is ill-suited for collecting the array of transients needed in 2D NMR spectroscopy. Spatially encoded single-scan 2D NMR methods can circumvent this drawback, yet these "ultrafast" experiments can cover spectral ranges of only approximately 20 ppm using conventional hardware. To deal with this limitation, we discuss here new spatial/spectral encoding strategies capable of folding (13)C resonances into the desired spectral windows. This new approach allows one to obtain--following a single hyperpolarization process--multiple 2D heteronuclear correlations arising from different (13)C regions. In combination with ex situ DNP, these principles enable the acquisition of HMBC and HSQC 2D NMR spectra on approximately 1 mM mixtures of natural products, characterizing with a high resolution sites spread over nearly 100 ppm bandwidths.

The so-called "ultrafast" nuclear magnetic resonance (NMR) methods enable the collection of multidimensional spectra within a single scan. These experiments operate by replacing traditional t(1) time increments, with a series of combined radiofrequency-irradiation/magnetic-field-gradient manipulations that spatially encode the effects of the indirect-domain spin interactions. Barring the presence of sizable displacements, the spatial patterns thus imparted can be read out following a mixing period with the aid of oscillating acquisition gradients, leading to a train of t(2)-modulated echoes carrying in their positions and phases the indirect- and the direct-domain spin interactions. Both the initial spatial encoding as well as the subsequent spatial decoding procedures underlying ultrafast NMR were designed under the assumption that spins remain static within the sample during their execution. Most often this is not the case, and motion-related effects can be expected to affect the outcome of these experiments. The present paper focuses on analyzing the effects of diffusion in ultrafast two-dimensional (2D) NMR. Toward this end both analytical and numerical formalisms are derived, capable of dealing with the nonuniform spin manipulations, macroscopic sample sizes, and microscopic displacements involved in this kind of sequences. After experimentally validating the correctness of these formalisms these were used to analyze the effects of diffusion for a variety of cases, including ultrafast experiments on both rapidly and slowly diffusing molecules. A series of prototypical schemes were considered including discrete and continuous encoding modes, constant- and real-time manipulations, homo- and heteronuclear acquisitions, and single versus multiple quantum modalities. The effects of molecular diffusion were also compared against typical relaxation-driven losses as they happen in these various prototypical situations; from all these situations, general guidelines for choosing the optimal ultrafast 2D NMR scheme for a particular sample and condition could be deduced.

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Multidimensional nuclear magnetic resonance (NMR) provides one of the foremost analytical tools available to elucidate the structure and dynamics of complex molecules in their native states. Executing this kind of experiment generally requires collecting an n-dimensional time-domain signal S, from which the spectrum arises via an appropriate Fourier analysis of its various time variables. This time-domain signal is actually measured directly only along one of the time axes, while the effects introduced by the remaining time variables are monitored via a parametric incrementation of their values throughout independent experiments. Two-dimensional (2D) NMR experiments thus usually require longer acquisition times than unidimensional experiments, 3D NMR is orders-of-magnitude more time consuming than 2D spectroscopy, etc. Very recently, we proposed and demonstrated an approach whereby data acquisition in 2D NMR can be parallelized, enabling the collection of complete 2D spectral sets within a single transient. The present paper discusses the extension of this 2D NMR methodology to an arbitrary number of dimensions. The principles of the ensuing ultrafast n-dimensional NMR approach are described, and a variety of homo- and heteronuclear 3D and 4D NMR spectra collected within a fraction of a second are presented.

Single-scan 2D NMR relies on a spatial axis for encoding the indirect-domain internal spin interactions. Various strategies have been demonstrated for fulfilling the needs underlying this procedure. All such schemes use gradient-echoed sequences that leave at their conclusion solely the effects of the internal interactions along the indirect domain; they also include a real-time scheme that though simple, yields in general mixed-phase line shapes. The present paper introduces two new proposals geared up for easing the spatial encoding underlying single-scan 2D NMR methodologies. One of these is capable of delivering dispersive-free peaks along the indirect domain, and thereby purely-absorptive 2D line shapes, in amplitude-encoded experiments. The other demonstrates for the first time, the possibility to obtain single-scan 2D spectra without echoing the effects of the encoding gradient-simply by applying a single-pulse frequency sweep to encode the interactions. Both of these modes are compatible with homo- and heteronuclear correlations, and exhibit a number of complementary features vis-à-vis encoding alternatives that have so far been presented. The overall principles underlying these new spatially encoding protocols are derived, and their performance demonstrated with single-scan 2D NMR TOCSY and HSQC experiments on model compounds.

Two-dimensional nuclear magnetic resonance (2D NMR) spectroscopy provides the means to extract diverse physical, chemical, and biological information at an atomic level. Conventional sampling schemes, however, may result in relatively long 2D experiments; this has stimulated the search for alternative, rapid acquisition schemes. Among the strategies that have been recently proposed for achieving this counts an "ultrafast" approach, relying on the spatial encoding of the indirect domain evolution to provide arbitrary spectra within a single scan. A common feature of all spatial encoding schemes hitherto described is their uniform encoding of a continuous bandwidth of indirect-domain frequencies, regardless of the chemical sites' spectral distribution within it. These very general conditions, however, are often associated with a number of tradeoffs and compromises in the spectral widths and resolutions that can be achieved for both the direct and indirect domains. This paper proposes a different strategy for single-scan acquisition of 2D spectra, which performs an optimal encoding by employing a priori information regarding the positions of NMR resonances along the indirect domain. We denote this as "spatial/spectral encoding"; the underlying principles of this new approach, together with experimental results based on uni- and multidimensional rf pulse schemes, are presented.