13C Dynamic Nuclear Polarization Using a Trimeric Gd3+ Complex as an Additive.

Nuclear magnetic resonance (NMR) spectroscopy is a key method for the determination of molecular structures. Due to its intrinsically high (i.e., atomistic) resolution and versatility, it has found numerous applications for investigating gases, liquids, and solids. However, liquid-state NMR has found little application for suspensions of solid particles as the resonances of such systems are excessively broadened, typically beyond the detection threshold. Herein, we propose a route to overcoming this critical limitation by enhancing the signals of particle suspensions by >3.000-fold using dissolution dynamic nuclear polarization (d-DNP) coupled with rapid solid precipitation. For the proof-of-concept series of experiments, we employed calcium phosphate (CaP) as a model system. By d-DNP, we boosted the signals of phosphate 31P spins before rapid CaP precipitation inside the NMR spectrometer, leading to the inclusion of the hyperpolarized phosphate into CaP-nucleated solid particles within milliseconds. With our approach, within only 1 s of acquisition time, we obtained spectra of biphasic systems, i.e., micrometer-sized dilute solid CaP particles coexisting with their solution-state precursors. Thus, this work is a step toward real-time characterization of the solid-solution equilibrium. Finally, integrating the hyperpolarized data with molecular dynamics simulations and electron microscopy enabled us to shed light on the CaP formation mechanism in atomistic detail.

Review: 194 refs.

Nuclear magnetic resonance (NMR) spectroscopy is a key technique for molecular structure determination in solution. However, due to its low sensitivity, many efforts have been made to improve signal strengths and reduce the required substrate amounts. In this regard, dissolution dynamic nuclear polarization (DDNP) is a versatile approach as signal enhancements of over 10 000-fold are achievable. Samples are signal-enhanced ex situ by transferring electronic polarization from radicals to nuclear spins before dissolving and shuttling the boosted sample to an NMR spectrometer for detection. However, the applicability of DDNP suffers from one major drawback, namely, paramagnetic relaxation enhancements (PREs) that critically reduce relaxation times due to the codissolved radicals. PREs are the primary source of polarization losses canceling the signal improvements obtained by DNP. We solve this problem by using potassium nitrosodisulfonate (Frémy's salt) as polarization agent (PA), which provides high nuclear spin polarization and allows for rapid scavenging under mild reducing conditions. We demonstrate the potential of Frémy's salt, (i) showing that both 1H and 13C polarization of ∼30% can be achieved and (ii) describing a hybrid sample shuttling system (HySSS) that can be used with any DDNP/NMR combination to remove the PA before NMR detection. This gadget mixes the hyperpolarized solution with a radical scavenger and injects it into an NMR tube, providing, within a few seconds, quantitatively radical-free, highly polarized solutions. The cost efficiency and broad availability of Frémy's salt might facilitate the use of DDNP in many fields of research.

Applications of Dissolution-DNP for NMR Screening.

Roofing membranes produced with ketone-ethylene-ester (KEE) and polyvinyl chloride (PVC) are defined within the standard specification for KEE-based sheet roofing, ASTM D6754, Standard Specification for Ketone Ethylene Ester Based Sheet Roofing, in which it is specified that such membranes must contain at least 50% (wt.) KEE. Until the recent release of ASTM D8154, Standard Test Methods for 1H-NMR Determination of Ketone-Ethylene-Ester and Polyvinyl Chloride Contents in KEE-PVC Roofing Fabrics, in which the determination of KEE content is based on nuclear magnetic resonance (NMR) spectroscopy, no method was sufficiently precise or accurate to measure the KEE content within 1% or better. In this paper, a description is provided of the development and the basic process behind the use of 1H-NMR to establish KEE content in KEE/PVC membranes as described in ASTM D8154. To develop a quantitative method to assess KEE concentration in roofing membranes, several NMR approaches were used, including both solid-state and liquid-state NMR. Approaches using solid-state NMR, including carbon-13 and proton spectroscopy, proved inadequate for the quantification of KEE because of insufficient spectral resolution. Liquid-state NMR proved to be a better approach, but accurate results are achieved only after the KEE-PVC blend is extracted from the roofing membrane through a multistep process. The liquid-state NMR work led to two methods to quantitatively measure the KEE content in blends with PVC. Method A is the simplest, and its accuracy is better than 2.3%. Method B is more protracted, but its accuracy is better than 0.6%.

A nuclear magnetic resonance advance. Imaging fluorinated anesthetics in the brain.

Solid Effect DNP in a Rapid-melt setup

Using liquid and solid state NMR and photoluminescence to study the synthesis and solubility properties of amine capped silicon nanoparticles

<sec>Near-zero-field nuclear magnetic resonance (NMR) has become a rapidly developing spectroscopic and imaging method, providing promising opportunities for portable diagnostics and fast chemical analysis. A key technology is the atomic magnetometer, and its ongoing improvements have sparked growing interest in potential clinical applications.</sec><sec>The near-zero-field NMR has long been limited by weak signal strength, but recent developments in the hyperpolarization method have provided an effective solution to this problem. Dissolution dynamic nuclear polarization (dDNP), parahydrogen-based polarization schemes (PHIP/SABRE), chemically induced dynamic nuclear polarization (CIDNP), and spin-exchange optical pumping (SEOP) have all demonstrated preliminary feasibility in this context.</sec><sec>By combining such hyperpolarization strategies with near-zero-field detection, strong signals can be obtained without the need of traditional high-field magnets. This capability opens new pathways for applying near-zero-field NMR to both chemical sensing and biomedical imaging, enabling compact tools for rapid analysis and diagnostic applications. Here, we review the recent progress of the intersection of near-zero-field NMR and hyperpolarization techniques.</sec>

Dynamic nuclear polarization (DNP) is a nuclear magnetic resonance (NMR) hyperpolarization technique that mediates polarization transfer from unpaired electrons to nuclear spins. DNP performance can vary significantly depending on the types of polarizing agents employed, and the criteria for optimum DNP efficiency are not fully understood. Thus, a better understanding of the structure, electron paramagnetic resonance (EPR) line widths, and relaxation properties would aid in designing more efficient DNP polarizing agents. However, EPR characterizations of the polarizing agents are typically performed in different environments (e.g., strength of magnetic field and microwave power) than typical DNP experiments. Here, we demonstrate a low-cost and home-built setup that enables in situ EPR detection in a dual resonance DNP-NMR/EPR probe using an optical chopper. The optical chopper modulates the microwave irradiation, thereby modulating the longitudinal magnetization (Mz) of the electron spins, which results in a LOngitudinal-Detected (LOD) EPR spectrum. The EPR spectrum acquired for TEMPOL at 6.7 T/188 GHz using a mechanical modulation showed a good agreement with the spectrum acquired using an electrical modulation. Hence, our work provides a proof-of-principle setup that enables an optical chopper EPR spectrometer.

The role of mixed state entanglement in liquid-state nuclear magnetic resonance (NMR) quantum computation is not yet well-understood. In particular, despite the success of quantum information processing with NMR, recent work has shown that quantum states used in most of those experiments were not entangled. This is because these states, derived by unitary transforms from the thermal equilibrium state, were too close to the maximally mixed state. We are thus motivated to determine whether a given NMR state is entanglable - that is, does there exist a unitary transform that entangles the state? The boundary between entanglable and nonentanglable thermal states is a function of the spin system size $N$ and its temperature $T$. We provide new bounds on the location of this boundary using analytical and numerical methods; our tightest bound scales as $N \sim T$, giving a lower bound requiring at least $N \sim 22,000$ proton spins to realize an entanglable thermal state at typical laboratory NMR magnetic fields. These bounds are tighter than known bounds on the entanglability of effective pure states.

In recent years, hyperpolarization of water protons via dissolution Dynamic Nuclear Polarization (dDNP) has attracted increasing interest in the magnetic resonance community. Hyperpolarized water may provide an alternative to Gd-based contrast agents for angiographic and perfusion Magnetic Resonance Imaging (MRI) examinations, and it may report on chemical and biochemical reactions and proton exchange while perfoming Nuclear Magnetic Resonance (NMR) investigations. However, hyperpolarizing water protons is challenging. The main reason is the presence of radicals, required to create the hyperpolarized nuclear spin state. Indeed, the radicals will also be the main source of relaxation during the dissolution and transfer to the NMR or MRI system. In this work, we report water magnetizations otherwise requiring a field of 10,000 T at room temperature on a sample of pure water, by employing dDNP via UV-generated, labile radicals. We demonstrate the potential of our methodology by acquiring a 15N spectrum from natural abundance urea with a single scan, after spontaneous magnetization transfer from water protons to nitrogen nuclei.

Solid-state nuclear magnetic resonance (NMR) spectroscopy is an atomic-level method used to determine the chemical structure, three-dimensional structure, and dynamics of solids and semi-solids. This Primer summarizes the basic principles of NMR as applied to the wide range of solid systems. The fundamental nuclear spin interactions and the effects of magnetic fields and radiofrequency pulses on nuclear spins are the same as in liquid-state NMR. However, because of the anisotropy of the interactions in the solid state, the majority of high-resolution solid-state NMR spectra is measured under magic-angle spinning (MAS), which has profound effects on the types of radiofrequency pulse sequences required to extract structural and dynamical information. We describe the most common MAS NMR experiments and data analysis approaches for investigating biological macromolecules, organic materials, and inorganic solids. Continuing development of sensitivity-enhancement approaches, including 1H-detected fast MAS experiments, dynamic nuclear polarization, and experiments tailored to ultrahigh magnetic fields, is described. We highlight recent applications of solid-state NMR to biological and materials chemistry. The Primer ends with a discussion of current limitations of NMR to study solids, and points to future avenues of development to further enhance the capabilities of this sophisticated spectroscopy for new applications.

Dissolution dynamic nuclear polarization (DNP) has become one of the predominant implementations for DNP. However, the technical implementation of transferring the sample from the polarizer to the nuclear magnetic resonance (NMR) system remains challenging. There is a need for additional technical optimizations in order to use dissolution DNP for biochemical and chemical applications. Here we show how a newly designed pressure dissolution kit considerably improves spectral quality and stability by enabling highly reliable and fast sample transfer to the NMR system.

Zero- and ultralow-field (ZULF) nuclear magnetic resonance (NMR) is an emerging tool for precision chemical analysis. Unlike conventional (high-field) NMR, which relies on chemical shifts for molecular identification, zero-field analog reports J-spectra that depend on the nuclear spin-spin coupling topology of molecules under investigation. While chemical shifts are usually a small fraction of the resonance frequencies, J-spectra for various spin systems are completely different from each other. In this work, we use zero-field NMR to study dynamic chemical processes and investigate the influence of chemical exchange on ZULF NMR spectra. We develop a computation approach that allows quantitative calculation of ZULF NMR spectra in the presence of chemical exchange and apply it to study aqueous solutions of [15N]ammonium as a model system. In this system, proton exchange rates span more than three orders of magnitude depending on acidity (pH), as monitored by high-field and ZULF NMR. We show that chemical exchange substantially affects the J-coupled NMR spectra and, in some cases, can lead to degradation and complete disappearance of the spectral features. To demonstrate potential applications of ZULF NMR for chemistry and biomedicine, we show a ZULF NMR spectrum of [2-13C]pyruvic acid hyperpolarized via dissolution dynamic nuclear polarization (dDNP). The metabolism of pyruvate provides valuable biochemical information and its monitoring by zero-field NMR could give spectral resolution that is hard to achieve at high magnetic fields. We foresee applications of affordable and scalable ZULF NMR coupled with hyperpolarization modalities to study chemical exchange phenomena in vivo and in situations where high-field NMR detection is not possible to implement.