A scheme enabling the complete sampling of multidimensional NMR domains within a single continuous acquisition is introduced and exemplified. Provided that an analyte's signal is sufficiently strong, the acquisition time of multidimensional NMR experiments can thus be shortened by orders of magnitude. This could enable the characterization of transient events such as proteins folding, 2D NMR experiments on samples being chromatographed, bring the duration of higher dimensional experiments (e.g., 4D NMR) into the lifetime of most proteins under physiological conditions, and facilitate the incorporation of spectroscopic 2D sequences intoin vivoimaging investigations. The protocol is compatible with existing multidimensional pulse sequences and can be implemented by using conventional hardware; its performance is exemplified here with a variety of homonuclear 2D NMR acquisitions.

In the Spring of 2013, NMR spectroscopists convened at the Weizmann Institute in Israel to brainstorm on approaches to improve the sensitivity of NMR experiments, particularly when applied in biomolecular settings. This multi‐author interdisciplinary Review presents a state‐of‐the‐art description of the primary approaches that were considered. Topics discussed included the future of ultrahigh‐field NMR systems, emerging NMR detection technologies, new approaches to nuclear hyperpolarization, and progress in sample preparation. All of these are orthogonal efforts, whose gains could multiply and thereby enhance the sensitivity of solid‐ and liquid‐state experiments. While substantial advances have been made in all these areas, numerous challenges remain in the quest of endowing NMR spectroscopy with the sensitivity that has characterized forms of spectroscopies based on electrical or optical measurements. These challenges, and the ways by which scientists and engineers are striving to solve them, are also addressed.

Metabolic fluxes can serve as specific biomarkers for detecting malignant transformations, tumor progression, and response to microenvironmental changes and treatment procedures. We present noninvasive hyperpolarized ¹³ C NMR investigations on the metabolic flux of pyruvate to lactate, in a well-controlled injection/perfusion system using T47D human breast cancer cells. Initial rates of pyruvate-to-lactate conversion were obtained by fitting the hyperpolarized ¹³ C and ancillary ³¹ P NMR data to a model, yielding both kinetic parameters and mechanistic insight into this conversion. Transport was found to be the rate-limiting process for the conversion of extracellular pyruvate to lactate with K _m = 2.14 ± 0.03 mM, typical of the monocarboxylate transporter 1 (MCT1), and a V _max = 27.6 ± 1.1 fmol·min ⁻¹ ·cell ⁻¹ , in agreement with the high expression level of this transporter. Modulation of the environment to hypoxic conditions as well as suppression of cells' perfusion enhanced the rate of pyruvate-to-lactate conversion, presumably by up-regulation of the MCT1. Conversely, the addition of quercetin, a flavonoidal MCT1 inhibitor, markedly reduces the apparent rate of pyruvate-to-lactate conversion. These results suggest that hyperpolarized ¹³ C ₁ -pyruvate may be a useful magnetic resonance biomarker of MCT regulation and malignant transformations in breast cancer.

Two-dimensional nuclear magnetic resonance (2D NMR) spectroscopy is widely used in chemical and biochemical analyses. Multidimensional NMR is also witnessing increased use in quantitative and metabolic screening applications. Conventional 2D NMR experiments, however, are affected by inherently long acquisition durations, arising from their need to sample the frequencies involved along their indirect domains in an incremented, scan-by-scan nature. A decade ago, a so-called ultrafast (UF) approach was proposed, capable of delivering arbitrary 2D NMR spectra involving any kind of homo- or heteronuclear correlation, in a single scan. During the intervening years, the performance of this subsecond 2D NMR methodology has been greatly improved, and UF 2D NMR is rapidly becoming a powerful analytical tool experiencing an expanded scope of applications. This review summarizes the principles and main developments that have contributed to the success of this approach and focuses on applications that have been recently demonstrated in various areas of analytical chemistry—from the real-time monitoring of chemical and biochemical processes, to extensions in hyphenated techniques and in quantitative applications.

Bulk ${}^{13}\mathrm{C}$ polarization can be strongly enhanced in diamond at room temperature based on the optical pumping of nitrogen-vacancy color centers. This effect was confirmed by irradiating single crystals at a $\sim 50\mathrm{mT}$ field promoting anticrossings between electronic excited-state levels, followed by shuttling of the sample into an NMR setup and by subsequent ${}^{13}\mathrm{C}$ detection. A nuclear polarization of $\sim 0.5\%$—equivalent to the ${}^{13}\mathrm{C}$ polarization achievable by thermal polarization at room temperature at fields of $\sim 2000\mathrm{T}$—was measured, and its bulk nature determined based on line shape and relaxation measurements. Positive and negative enhanced polarizations were obtained, with a generally complex but predictable dependence on the magnetic field during optical pumping. Owing to its simplicity, this ${}^{13}\mathrm{C}$ room temperature polarizing strategy provides a promising new addition to existing nuclear hyperpolarization techniques.