Hyperpolarised benchtop NMR spectroscopy for analytical applications.

Benchtop NMR spectrometers, with moderate magnetic field strengths (B=1-2.4T) and sub-ppm chemical shift resolution, are an affordable and portable alternative to standard laboratory NMR (B≥7T). However, in moving to lower magnetic field instruments, sensitivity and chemical shift resolution are significantly reduced.

Improved benchtop P NMR reaction monitoring Multi-Resonance SHARPER.

reaction monitoring of hydrogenation reactions featuring oxygen-sensitive organometallic complexes is done a P benchtop NMR spectrometer using the Multi-Resonance Sensitive Homogeneous And Resolved PEaks in Real time (MR-SHARPER) sequence. Signal enhancement generated by MR-SHARPER enables monitoring of reactivity on the order of minutes that could not be followed with traditional P{H} NMR detection.

Quantitative reaction monitoring using hydrogen-enhanced benchtop NMR spectroscopy.

The hydrogen-induced polarisation (PHIP) NMR signal enhancement technique is used to study H addition to Vaska's complex (-[IrCl(CO)(PPh)]) with both standard high-field (9.4 T) NMR and benchtop (1 T) NMR detection. Accurate and repeatable rate constants of (0.

Enhancing F Benchtop NMR Spectroscopy by Combining -Hydrogen Hyperpolarization and Multiplet Refocusing.

Benchtop NMR spectrometers provide a promising alternative to high-field NMR for applications that are limited by instrument size and/or cost. F benchtop NMR is attractive due to the larger chemical shift range of F relative to H and the lack of background signal in most applications. However, practical applications of benchtop F NMR are limited by its low sensitivity due to the relatively weak field strengths of benchtop NMR spectrometers.

SHARPER-enhanced benchtop NMR: improving SNR by removing couplings and approaching natural linewidths.

We present a signal enhancement strategy for benchtop NMR that produces SNR increases on the order of 10 to 30 fold by collapsing the target resonance into an extremely narrow singlet. Importantly, the resultant signal is amenable to quantitative interpretation and therefore can be applied to analytical applications such as reaction monitoring.

Rapid C NMR hyperpolarization delivered from -hydrogen enables the low concentration detection and quantification of sugars.

Monosaccharides, such as glucose and fructose, are important to life. In this work we highlight how the rapid delivery of improved C detectability for sugars by nuclear magnetic resonance (NMR) can be achieved using the -hydrogen based NMR hyperpolarization method SABRE-Relay (Signal Amplification by Reversible Exchange-Relay). The significant C signal enhancements of 250 at a high field of 9.

In Situ SABRE Hyperpolarization with Earth's Field NMR Detection.

Hyperpolarization methods, which increase the sensitivity of nuclear magnetic resonance (NMR) and magnetic resonance imaging (MRI), have the potential to expand the range of applications of these powerful analytical techniques and to enable the use of smaller and cheaper devices. The signal amplification by reversible exchange (SABRE) method is of particular interest because it is relatively low-cost, straight-forward to implement, produces high-levels of renewable signal enhancement, and can be interfaced with low-cost and portable NMR detectors. In this work, we demonstrate an in situ approach to SABRE hyperpolarization that can be achieved using a simple, commercially-available Earth's field NMR detector to provide H polarization levels of up to 3.

Towards measuring reactivity on micro-to-millisecond timescales with laser pump, NMR probe spectroscopy.

We present a quantitative analysis of the timescales of reactivity that are accessible to a laser pump, NMR probe spectroscopy method using para-hydrogen induced polarisation (PHIP) and identify three kinetic regimes: fast, intermediate and slow. These regimes are defined by the relative rate of reaction, k, compared to δω, the frequency of the NMR signal oscillations associated with the coherent evolution of the hyperpolarised 1H NMR signals created after para-hydrogen (p-H2) addition during the pump-probe delay. The kinetic regimes are quantitatively defined by a NMR dephasing parameter, ε = δω/k.

Reaction Monitoring Using SABRE-Hyperpolarized Benchtop (1 T) NMR Spectroscopy.

The conversion of [IrCl(COD)(IMes)] (COD = cis, cis-1,5-cyclooctadiene, IMes = 1,3-bis(2,4,6-trimethyl-phenyl)imidazole-2-ylidene) in the presence of an excess of para-hydrogen ( p-H) and a substrate (4-aminopyridine (4-AP) or 4-methylpyridine (4-MP)) into [Ir(H)(IMes)(substrate)]Cl is monitored by H NMR spectroscopy using a benchtop (1 T) spectrometer in conjunction with the p-H-based hyperpolarization technique signal amplification by reversible exchange (SABRE). A series of single-shot H NMR measurements are used to monitor the chemical changes that take place in solution through the lifetime of the hyperpolarized response. Non-hyperpolarized high-field H NMR control measurements were also undertaken to confirm that the observed time-dependent changes relate directly to the underlying chemical evolution.

Quantification of hyperpolarisation efficiency in SABRE and SABRE-Relay enhanced NMR spectroscopy.

para-Hydrogen (p-H) induced polarisation (PHIP) is an increasingly popular method for sensitivity enhancement in NMR spectroscopy. Its growing popularity is due in part to the introduction of the signal amplification by reversible exchange (SABRE) method that generates renewable hyperpolarisation in target analytes in seconds. A key benefit of PHIP and SABRE is that p-H can be relatively easily and cheaply produced, with costs increasing with the desired level of p-H purity.

Quantitative In Situ Monitoring of Parahydrogen Fraction Using Raman Spectroscopy.

Raman spectroscopy has been used to provide a rapid, noninvasive, and nondestructive quantification method for determining the parahydrogen fraction of hydrogen gas. The basis of the method is the measurement of the ratio of the first two rotational bands of hydrogen at 355 cm and 586 cm corresponding to parahydrogen and orthohydrogen, respectively. The method has been used to determine the parahydrogen content during a production process and a reaction.

SABRE hyperpolarization enables high-sensitivity H and C benchtop NMR spectroscopy.

Benchtop NMR spectrometers operating with low magnetic fields of 1-2 T at sub-ppm resolution show great promise as analytical platforms that can be used outside the traditional laboratory environment for industrial process monitoring. One current limitation that reduces the uptake of benchtop NMR is associated with the detection fields' reduced sensitivity. Here we demonstrate how para-hydrogen (p-H2) based signal amplification by reversible exchange (SABRE), a simple to achieve hyperpolarization technique, enhances agent detectability within the environment of a benchtop (1 T) NMR spectrometer so that informative 1H and 13C NMR spectra can be readily recorded for low-concentration analytes.

Refocused linewidths less than 10 Hz in H solid-state NMR.

Coherence lifetimes in homonuclear dipolar decoupled H solid-state NMR experiments are usually on the order of a few ms. We discover an oscillation that limits the lifetime of the coherences by recording spin-echo dephasing curves. We find that this oscillation can be removed by the application of a double spin-echo experiment, leading to coherence lifetimes of more than 45 ms in adamantane and more that 22 ms in β-AspAla, corresponding to refocused linewidths of less than 7 and 14 Hz respectively.

A simple hand-held magnet array for efficient and reproducible SABRE hyperpolarisation using manual sample shaking.

Signal amplification by reversible exchange (SABRE) is a hyperpolarisation technique that catalytically transfers nuclear polarisation from parahydrogen, the singlet nuclear isomer of H , to a substrate in solution. The SABRE exchange reaction is carried out in a polarisation transfer field (PTF) of tens of gauss before transfer to a stronger magnetic field for nuclear magnetic resonance (NMR) detection. In the simplest implementation, polarisation transfer is achieved by shaking the sample in the stray field of a superconducting NMR magnet.

Photochemical pump and NMR probe to monitor the formation and kinetics of hyperpolarized metal dihydrides.

On reaction of IrI(CO)(PPh) with para-hydrogen (-H), Ir(H)I(CO)(PPh) is formed which exhibits strongly enhanced H NMR signals for its hydride resonances. Complex also shows similar enhancement of its NMR spectra when it is irradiated under -H. We report the use of this photochemical reactivity to measure the kinetics of H addition by laser-synchronized reactions in conjunction with NMR.

Coherent evolution of parahydrogen induced polarisation using laser pump, NMR probe spectroscopy: Theoretical framework and experimental observation.

We recently reported a pump-probe method that uses a single laser pulse to introduce parahydrogen (p-H) into a metal dihydride complex and then follows the time-evolution of the p-H-derived nuclear spin states by NMR. We present here a theoretical framework to describe the oscillatory behaviour of the resultant hyperpolarised NMR signals using a product operator formalism. We consider the cases where the p-H-derived protons form part of an AX, AXY, AXYZ or AA'XX' spin system in the product molecule.

Protein dynamics. Direct observation of hierarchical protein dynamics.

One of the fundamental challenges of physical biology is to understand the relationship between protein dynamics and function. At physiological temperatures, functional motions arise from the complex interplay of thermal motions of proteins and their environments. Here, we determine the hierarchy in the protein conformational energy landscape that underlies these motions, based on a series of temperature-dependent magic-angle spinning multinuclear nuclear-magnetic-resonance relaxation measurements in a hydrated nanocrystalline protein.

Macroscopic nuclear spin diffusion constants of rotating polycrystalline solids from first-principles simulation.

A method for quantitatively calculating nuclear spin diffusion constants directly from crystal structures is introduced. This approach uses the first-principles low-order correlations in Liouville space (LCL) method to simulate spin diffusion in a box, starting from atomic geometry and including both magic-angle spinning (MAS) and powder averaging. The LCL simulations are fit to the 3D diffusion equation to extract quantitative nuclear spin diffusion constants.

Photochemical pump and NMR probe: chemically created NMR coherence on a microsecond time scale.

We report pump-probe experiments employing laser-synchronized reactions of para-hydrogen (para-H2) with transition metal dihydride complexes in conjunction with nuclear magnetic resonance (NMR) detection. The pump-probe experiment consists of a single nanosecond laser pump pulse followed, after a precisely defined delay, by a single radio frequency (rf) probe pulse. Laser irradiation eliminates H2 from either Ru(PPh3)3(CO)(H)2 1 or cis-Ru(dppe)2(H)2 2 in C6D6 solution.

Improved phase-modulated homonuclear dipolar decoupling for solid-state NMR spectroscopy from symmetry considerations.

We explore the effects of symmetry on the performance of phase-modulated homonuclear dipolar decoupling in (1)H solid-state NMR. We demonstrate that the symmetry of the DUMBO family of decoupling sequences is the result of two well-defined symmetry expansions. The first is an antipalindromic expansion that arises from the symmetrization step that was built into the original architecture of the DUMBO sequence.

Quasi-equilibria in reduced Liouville spaces.

The quasi-equilibrium behaviour of isolated nuclear spin systems in full and reduced Liouville spaces is discussed. We focus in particular on the reduced Liouville spaces used in the low-order correlations in Liouville space (LCL) simulation method, a restricted-spin-space approach to efficiently modelling the dynamics of large networks of strongly coupled spins. General numerical methods for the calculation of quasi-equilibrium expectation values of observables in Liouville space are presented.

A common theory for phase-modulated homonuclear decoupling in solid-state NMR.

We propose a new framework for homonuclear dipolar decoupling in solid-state NMR that provides a theoretical link between the FSLG, PMLG and DUMBO families. We show that through the use of a Legendre polynomial basis, the phase modulation of these decoupling schemes can be described by the same set of parameters, permitting for the first time a direct theoretical comparison between these methods. Use of this common basis reveals that the central decoupling mechanism is the same for DUMBO and FSLG/PMLG and that a similar vector picture can be used to describe both methods.

Quantitative analysis of Earth's field NMR spectra of strongly-coupled heteronuclear systems.

In the Earth's magnetic field, it is possible to observe spin systems consisting of unlike spins that exhibit strongly coupled second-order NMR spectra. Such spectra result when the J-coupling between two unlike spins is of the same order of magnitude as the difference in their Larmor precession frequencies. Although the analysis of second-order spectra involving only spin-(1/2) nuclei has been discussed since the early days of NMR spectroscopy, NMR spectra involving spin-(1/2) nuclei and quadrupolar (I>(1/2)) nuclei have rarely been treated.

A dynamic nuclear polarization strategy for multi-dimensional Earth's field NMR spectroscopy.

Dynamic nuclear polarization (DNP) is introduced as a powerful tool for polarization enhancement in multi-dimensional Earth's field NMR spectroscopy. Maximum polarization enhancements, relative to thermal equilibrium in the Earth's magnetic field, are calculated theoretically and compared to the more traditional prepolarization approach for NMR sensitivity enhancement at ultra-low fields. Signal enhancement factors on the order of 3000 are demonstrated experimentally using DNP with a nitroxide free radical, TEMPO, which contains an unpaired electron which is strongly coupled to a neighboring (14)N nucleus via the hyperfine interaction.