Dynamic Nuclear Polarization Enhancement Research Articles

Dipolar Order Induced Electron Spin Hyperpolarization.

The structure of coupled electron spin systems is of fundamental interest to many applications, including dynamic nuclear polarization (DNP), enhanced nuclear magnetic resonance (NMR), the generation of electron spin qubits for quantum information science (QIS), and quantitative studies of paramagnetic systems by electron paramagnetic resonance (EPR). However, the characterization of electron spin coupling networks is nontrivial, especially at high magnetic fields. This study focuses on a system containing high concentrations of trityl radicals that give rise to a DNP enhancement profile of 1H NMR characteristic of the presence of electron spin clusters. When this system is subject to selective microwave saturation through pump-probe ELectron DOuble Resonance (ELDOR) experiments, electron spin hyperpolarization is observed. We show that the generation of an out-of-equilibrium longitudinal dipolar order is responsible for the transient hyperpolarization of electron spins. Notably, the coupled electron spin system needs to form an AX-like system (where the difference in the Zeeman interactions of two spins is larger than their coupling interaction) such that selective microwave irradiation can generate signatures of electron spin hyperpolarization. We show that the extent of dipolar order, as manifested in the extent of electron spin hyperpolarization generated, can be altered by tuning the pump or probe pulse length, or the interpulse delay in ELDOR experiments that change the efficiency to generate or readout longitudinal dipolar order. Pump-probe ELDOR with selective saturation is an effective means for characterizing coupled electron spins forming AX-type spin systems that are foundational for DNP and quantum sensing.

Formation of Stable Radicals by Mechanochemistry and Their Application for Magic Angle Spinning Dynamic Nuclear Polarization Solid-State NMR Spectroscopy.

High-field magic angle spinning (MAS) dynamic nuclear polarization (DNP) is becoming a common technique for improving the sensitivity of solid-state nuclear magnetic resonance (SSNMR) by the hyperpolarization of nuclear spins. Recently, we have shown that gamma irradiation is capable of creating long-lived free radicals that are amenable to MAS DNP in quartz and a variety of organic solids. Here, we demonstrate that ball milling is able to generate millimolar concentrations of stable radical species in diverse materials such as polystyrene, cellulose, borosilicate glass, and fused quartz. High-field electron paramagnetic resonance (EPR) was used to obtain further insight into the nature of the radicals formed in ball milled quartz and borosilicate glass. We further show that radicals generated in quartz by ball milling can be used for solid-effect DNP. We obtained 29Si DNP enhancements of approximately 114 and 33 at 110 K and room temperature, respectively, from a sample of ball milled quartz.

High-frequency high-power DNP/EPR spectrometer operating at 7 T magnetic field

One of the most essential prerequisites for the development of pulse Dynamic Nuclear Polarization (DNP) is the ability to generate high-power coherent mm-wave pulses at the electron precession frequencies corresponding to the magnetic fields of modern high-resolution NMR spectrometers. As a major step towards achieving this goal, an Extended Interaction Klystron (EIK) pulse amplifier custom-built by the Communications and Power Industries, Inc. and producing up to 140 W at 197.8 GHz, was integrated with in-house built NMR/DNP/EPR spectrometer operating at 7 T magnetic field. The spectrometer employs a Thomas Keating, Ltd. quasioptical bridge to direct mm-waves into a homebuilt DNP probe incorporating photonic bandgap (PBG) resonators to further boost electronic B1e fields. Three-pulse electron spin echo nutation experiments were employed to characterize the B1e fields at the sample by operating the homodyne 198 GHz bridge in an induction mode. Room-temperature experiments with a single-crystal high-pressure, high-temperature (HPHT) diamond and a polystyrene film doped with BDPA radical yielded < 9 ns π/2 pulses at ca. 50 W specified EIK output at the corresponding resonance frequencies and the PBG resonator quality factor of Q≈300. DNP experiments carried out in a “gated” mode by supplying 20 μs mm-wave pulses every 1 ms yielded 13C solid-effect DNP with gains up to 20 for the polystyrene-BDPA sample at natural 13C abundance. For a single-crystal HPHT diamond, the gated DNP mode yielded almost the same 13C enhancement as a low-power continuous wave (CW) mode at 0.4 W, whereas no DNP effect was observed for the BDPA/polystyrene sample in the latter case. To illustrate the versatility of our upgraded DNP spectrometer, room-temperature Overhauser DNP enhancements of 7–14 for 31P NMR signal were demonstrated using a liquid droplet of 1 M tri-phenyl phosphine co-dissolved with 100 mM of BDPA in toluene‑d8.

Optimal sensitivity for 1H detected relayed DNP of organic solids at fast MAS

Dynamic nuclear polarization (DNP) combined with high magnetic fields and fast magic angle spinning (MAS) has opened up a new avenue for the application of exceptionally sensitive 1H NMR detection schemes to study protonated solids. Recently, it has been shown that DNP experiments at fast MAS rates lead to slower spin diffusion and hence reduced DNP enhancements for impregnated materials. However, DNP enhancements alone do not determine the overall sensitivity of a NMR experiment. Here we measure the overall sensitivity of one-dimensional 1H detected relayed DNP experiments as a function of the MAS rate in the 20–60 kHz regime using 0.7 mm diameter rotors at 21.2 T. Although faster MAS rates are detrimental for the DNP enhancement on the target material, due to slower spin diffusion, we find that with increasing spinning rates the gain in sensitivity due to 1H line-narrowing and the folding-in of sideband intensity compensates a large part of the loss of overall hyperpolarization. We find that sensitivity depends on the atomic site in the molecule, and is maximised at between 40 and 50 kHz MAS for the sample of L-histidine.HCl·H2O studied here. There is a 10–20 % difference in sensitivity between the optimum MAS rate and the fastest rate currently accessible (60 kHz).

Rational Design of Dinitroxide Polarizing Agents for Dynamic Nuclear Polarization to Enhance Overall NMR Sensitivity.

We evaluate the overall sensitivity gains provided by a series of eighteen nitroxide biradicals for dynamic nuclear polarization (DNP) solid-state NMR at 9.4 T and 100 K, including eight new biradicals. We find that in the best performing group the factors contributing to the overall sensitivity gains, namely the DNP enhancement, the build-up time, and the contribution factor, often compete with each other leading to very similar overall sensitivity across a range of biradicals. NaphPol and HydroPol are found to provide the best overall sensitivity factors, in organic and aqueous solvents respectively. One of the new biradicals, AMUPolCbm, provides high sensitivity for all three solvent formulations measured here, and can be considered to be a "universal" polarizing agent.

Rational Design of Dinitroxide Polarizing Agents for Dynamic Nuclear Polarization to Enhance Overall NMR Sensitivity

AbstractWe evaluate the overall sensitivity gains provided by a series of eighteen nitroxide biradicals for dynamic nuclear polarization (DNP) solid‐state NMR at 9.4 T and 100 K, including eight new biradicals. We find that in the best performing group the factors contributing to the overall sensitivity gains, namely the DNP enhancement, the build‐up time, and the contribution factor, often compete with each other leading to very similar overall sensitivity across a range of biradicals. NaphPol and HydroPol are found to provide the best overall sensitivity factors, in organic and aqueous solvents respectively. One of the new biradicals, AMUPolCbm, provides high sensitivity for all three solvent formulations measured here, and can be considered to be a “universal” polarizing agent.

The solid effect of dynamic nuclear polarization in liquids - accounting for g-tensor anisotropy at high magnetic fields.

In spite of its name, the solid effect of dynamic nuclear polarization (DNP) is also operative in viscous liquids, where the dipolar interaction between the polarized nuclear spins and the polarizing electrons is not completely averaged out by molecular diffusion on the timescale of the electronic spin-spin relaxation time. Under such slow-motional conditions, it is likely that the tumbling of the polarizing agent is similarly too slow to efficiently average the anisotropies of its magnetic tensors on the timescale of the electronic . Here we extend our previous analysis of the solid effect in liquids to account for the effect of -tensor anisotropy at high magnetic fields. Building directly on the mathematical treatment of slow tumbling in electron spin resonance , we calculate solid-effect DNP enhancements in the presence of both translational diffusion of the liquid molecules and rotational diffusion of the polarizing agent. To illustrate the formalism, we analyze high-field (9.4 T) DNP enhancement profiles from nitroxide-labeled lipids in fluid lipid bilayers. By properly accounting for power broadening and motional broadening, we successfully decompose the measured DNP enhancements into their separate contributions from the solid and Overhauser effects.

The solid effect of dynamic nuclear polarization in liquids.

The solid-state effect of dynamic nuclear polarization (DNP) is operative also in viscous liquids where the dipolar interaction between the electronic and nuclear spins is partially averaged. The proper way to quantify the degree of averaging, and thus calculate the efficiency of the effect, should be based on the time-correlation function of the dipolar interaction. Here we use the stochastic Liouville equation formalism to develop a general theoretical description of the solid effect in liquids. The derived expressions can be used with different dipolar correlations functions depending on the assumed motional model. At high magnetic fields, the theory predicts DNP enhancements at small offsets, far from the classical solid-effect positions that are displaced by one nuclear Larmor frequency from the electronic resonance. The predictions are in quantitative agreement with such enhancement peaks observed at 9.4 T . These non-canonical peaks are not due to thermal mixing or the cross effect but exactly follow the dispersive component of the EPR line.

Non-perturbative treatment of the solid effect of dynamic nuclear polarization.

In the solid effect of dynamic nuclear polarization (DNP), the concerted flips of the electronic and nuclear spins, which are needed for polarization transfer, are induced by the microwaves. Commonly, the effect of the microwaves is modeled by a rate process whose rate constant is determined perturbatively. According to quantum mechanics, however, the coherent microwave excitation leads to Rabi nutation, which corresponds to a rotation rather than a rate process. Here we reconcile the coherent effect of the microwaves with the description by rate equations by focusing only on the steady state of the spin dynamics. We show that the phenomenological rate constants describing the synchronous excitation of the electronic and nuclear spins can be selected such that the description by rate equations yields the same steady state as the exact quantum-mechanical treatment. The resulting non-perturbative rates differ from the classical, perturbative ones and remain valid also at the high microwave powers used in modern-day DNP. Our treatment of the solid effect highlights the role of the coherences in the mechanistic steps of polarization transfer and reveals the importance of the dispersive (i.e., out-of-phase) component of the EPR line. Interestingly, the multiplicative dependence of the DNP enhancement on the dispersive EPR component was intuited in the very first report of the solid effect in liquids . The time-domain description of the solid effect developed here is extendable to liquids, where the dipolar interaction changes randomly in time due to molecular diffusion.

Anle138b interaction in α-synuclein aggregates by dynamic nuclear polarization NMR.

Small molecules that bind to oligomeric protein species such as membrane proteins and fibrils are of clinical interest for development of therapeutics and diagnostics. Definition of the binding site at atomic resolution via NMR is often challenging due to low binding stoichiometry of the small molecule. For fibrils and aggregation intermediates grown in the presence of lipids, we report atomic-resolution contacts to the small molecule at sub nm distance via solid-state NMR using dynamic nuclear polarization (DNP) and orthogonally labelled samples of the protein and the small molecule. We apply this approach to α-synuclein (αS) aggregates in complex with the small molecule anle138b, which is a clinical drug candidate for disease modifying therapy. The small central pyrazole moiety of anle138b is detected in close proximity to the protein backbone and differences in the contacts between fibrils and early intermediates are observed. For intermediate species, the 100K condition for DNP helps to preserve the aggregation state, while for both fibrils and oligomers, the DNP enhancement is essential to obtain sufficient sensitivity.

Coherent Dynamic Nuclear Polarization using Chirped Pulses.

This paper presents a study of coherent dynamic nuclear polarization (DNP) using frequency swept pulses at 94 GHz which optimize the polarization transfer efficiency. Accordingly, an enhancement ε ∼ 496 was observed using 10 mM trityl-OX063 as the polarizing agent in a standard 6:3:1 d8-glycerol/D2O/H2O glassing matrix at 70 K. At present, this is the largest DNP enhancement reported at this microwave frequency and temperature. Furthermore, the frequency swept pulses enhance the nuclear magnetic resonance (NMR) signal and reduce the recycle delay, accelerating the NMR signal acquisition.

Solid-Effect Dynamic Nuclear Polarization in Viscous Liquids at 9.4 T Using Narrow-Line Polarizing Agents.

Dynamic nuclear polarization (DNP) is a hyperpolarization method that is widely used for increasing the sensitivity of nuclear magnetic resonance (NMR) experiments. DNP is efficient in solid-state and liquid-state NMR, but its implementation in the intermediate state, namely, viscous media, is still less explored. Here, we show that a 1H DNP enhancement of over 50 can be obtained in viscous liquids at a magnetic field of 9.4 T and a temperature of 315 K. This was accomplished by using narrow-line polarizing agents in glycerol, both the water-soluble α,γ-bisdiphenylen-β-phenylallyl (BDPA) and triarylmethyl radicals, and a microwave/RF double-resonance probehead. We observed DNP enhancements with a field profile indicative of the solid effect and investigated the influence of microwave power, temperature, and concentration on the 1H NMR results. To demonstrate potential applications of this new DNP approach for chemistry and biology, we show hyperpolarized 1H NMR spectra of tripeptides, triglycine, and glypromate, in glycerol-d8.

Control and Manipulation of Microwave Polarization and Power of a Frequency-Agile 198 GHz Gyrotron for Magnetic Resonance

The measurement and manipulation of the microwave polarization emitted from a frequency-agile 198 GHz gyrotron for dynamic nuclear polarization (DNP) are demonstrated. In general, gyrotrons emit linearly polarized radiation, yet in this case elliptical polarization is observed from the 198 GHz gyrotron window. Indeed, half of the microwave power is circularly polarized while the other half is linearly polarized with a polarization of 60∘ with respect to the horizontal plane. For optimal use of microwave power for DNP experiments, the elliptical polarization from the gyrotron is converted into circular polarization with a Martin-Puplett interferometer (MPI). The dependence of the DNP enhancement on the microwave polarization was investigated by modifying the microwave polarization with the MPI. In addition, the MPI can generate a linearly polarized beam, which holds promise for future development of induction-mode electron spin detected experiments.

Observing Nearby Nuclei on Paramagnetic Trityls and MOFs via DNP and Electron Decoupling.

Dynamic nuclear polarization (DNP) is an NMR sensitivity enhancement technique that mediates polarization transfer from unpaired electrons to NMR-active nuclei. Despite its success in elucidating important structural information on biological and inorganic materials, the detailed polarization-transfer pathway from the electrons to the nearby and then the bulk solvent nuclei, and finally to the molecules of interest-remains unclear. In particular, the nuclei in the paramagnetic polarizing agent play significant roles in relaying the enhanced NMR polarizations to more remote nuclei. Despite their importance, the direct NMR observation of these nuclei is challenging because of poor sensitivity. Here, we show that a combined DNP and electron decoupling approach can facilitate direct NMR detection of these nuclei. We achieved an ∼80 % improvement in NMR intensity via electron decoupling at 0.35 T and 80 K on trityl radicals. Moreover, we recorded a DNP enhancement factor of ∼90 and ∼11 % higher NMR intensity using electron decoupling on paramagnetic metal-organic framework, magnesium hexaoxytriphenylene (MgHOTP MOF).

Biradical Polarizing Agents at High Fields.

The sensitivity enhancements available from dynamic nuclear polarization (DNP) are rapidly reshaping the research landscape and expanding the field of nuclear magnetic resonance (NMR) spectroscopy as a tool for solving complex chemical and structural problems. The past decade has seen considerable advances in this burgeoning method, while efforts to further improve its capabilities continue along many avenues. In this report, we examine the influence of static magnetic field strength and temperature on the reported 1H DNP enhancements from three conventional organic biradicals: TOTAPOL, AMUPol, and SPIROPOL. In contrast to the conventional wisdom, our findings show that at liquid nitrogen temperatures and 700 MHz/460.5 GHz, these three bisnitroxides all provide similar 1H DNP enhancements, ε ≈ 60. Furthermore, we investigate the influence of temperature, microwave power, magnetic field strength, and protein sample deuteration on the NMR experimental results.

Large Room Temperature Bulk DNP of 13C via P1 Centers in Diamond.

We use microwave-induced dynamic nuclear polarization (DNP) of the substitutional nitrogen defects (P1 centers) in diamond to hyperpolarize bulk 13C nuclei in both single crystal and powder samples at room temperature at 3.34 T. The large (>100-fold) enhancements demonstrated correspond to a greater than 10 000-fold improvement in terms of signal averaging of the 1% abundant 13C spins. The DNP was performed using low-power solid state sources under static (nonspinning) conditions. The DNP spectrum (DNP enhancement as a function of microwave frequency) of diamond powder shows features that broadly correlate with the EPR spectrum. A well-defined negative Overhauser peak and two solid effect peaks are observed for the central (mI = 0) manifold of the 14N spins. Previous low temperature measurements in diamond had measured a positive Overhauser enhancement in this manifold. Frequency-chirped millimeter-wave excitation of the electron spins is seen to significantly improve the enhancements for the two outer nuclear spin manifolds (mI = ±1) and to blur some of the sharper features associated with the central manifold. The outer lines are best fit using a combination of the cross effect and the truncated cross effect, which is known to mimic features of an Overhauser effect. Similar features are also observed in experiments on single crystal samples. The observation of all of these mechanisms in a single material system under the same experimental conditions is likely due to the significant heterogeneity of the high pressure, high temperature (HPHT) type Ib diamond samples used. Large room temperature DNP enhancements at fields above a few tesla enable spectroscopic studies with better chemical shift resolution under ambient conditions.

Room temperature DNP of diamond powder using frequency modulation

Dynamic nuclear polarization (DNP) is a method of enhancing NMR signals via the transfer of polarization from electron spins to nuclear spins using microwave (MW) irradiation. In most cases, monochromatic continuous-wave (MCW) MW irradiation is used. Recently, several groups have shown that frequency modulation of the MW irradiation can result in an additional increase in DNP enhancement above that obtained with MCW. The effect of frequency modulation on the solid effect (SE) and the cross effect (CE) has previously been studied using the stable organic radical 4-hydroxy TEMPO (TEMPOL) at temperatures under 20 K. Here, in addition to the SE and CE, we discuss the effect of frequency modulation on the Overhauser effect (OE) and the truncated CE (tCE) in the room-temperature 13C-DNP of diamond powders. We recently showed that diamond powders can exhibit multiple DNP mechanisms simultaneously due to the heterogeneity of P1 (substitutional nitrogen) environments within diamond crystallites. We explore how the two parameters that define the frequency modulation: (i) the Modulation frequency, fm (how fast the microwave frequency is varied) and (ii) the Modulation amplitude, Δω (the magnitude of the change in microwave frequency) influence the enhancement obtained via each mechanism. Frequency modulation during DNP not only allows us to improve DNP enhancement, but also gives us a way to control which DNP mechanism is most active. By choosing the appropriate modulation parameters, we can selectively enhance some mechanisms while simultaneously suppressing others.

1H Hyperpolarization of Solutions by Overhauser Dynamic Nuclear Polarization with 13C–1H Polarization Transfer

Dynamic nuclear polarization (DNP) is a method that can significantly increase the sensitivity of nuclear magnetic resonance. The only effective DNP mechanism for in situ hyperpolarization in solution is Overhauser DNP, which is inefficient for 1H at high magnetic fields. Here we demonstrate the possibility of generating significant 1H hyperpolarization in solution at room temperature. To counter the poor direct 1H Overhauser DNP, we implement steady-state 13C Overhauser DNP in solutions and then transfer the 13C hyperpolarization to 1H via a reverse insensitive nuclei enhanced by polarization transfer scheme. We demonstrate this approach using a 400 MHz gyrotron-equipped 3.2 mm magic angle spinning DNP system to obtain 1H DNP enhancement factors of 48, 8, and 6 for chloroform, tetrachloroethane, and phenylacetylene, respectively, at room temperature.

Dynamic Nuclear Polarization Enables NMR of Surface Passivating Agents on Hybrid Perovskite Thin Films.

Surface and bulk molecular modulators are the key to improving the efficiency and stability of hybrid perovskite solar cells. However, due to their low concentration, heterogeneous environments, and low sample mass, it remains challenging to characterize their structure and dynamics at the atomic level, as required to establish structure–activity relationships. Nuclear magnetic resonance (NMR) spectroscopy has revealed a wealth of information on the atomic-level structure of hybrid perovskites, but the inherent insensitivity of NMR severely limits its utility to characterize thin-film samples. Dynamic nuclear polarization (DNP) can enhance NMR sensitivity by orders of magnitude, but DNP methods for perovskite materials have so far been limited. Here, we determined the factors that limit the efficiency of DNP NMR for perovskite samples by systematically studying layered hybrid perovskite analogues. We find that the fast-relaxing dynamic cation is the major impediment to higher DNP efficiency, while microwave absorption and particle morphology play a secondary role. We then show that the former can be mitigated by deuteration, enabling 1H DNP enhancement factors of up to 100, which can be harnessed to enhance signals from dopants or additives present in very low concentrations. Specifically, using this new DNP methodology at a high magnetic field and with small sample volumes, we have recorded the NMR spectrum of the 20 nm (6 μg) passivating layer on a single perovskite thin film, revealing a two-dimensional (2D) layered perovskite structure at the surface that resembles the n = 1 homologue but which has greater disorder than in bulk layered perovskites.

Design Principles for the Development of Gd(III) Polarizing Agents for Magic Angle Spinning Dynamic Nuclear Polarization

Nuclear magnetic resonance suffers from an intrinsically low sensitivity, which can be overcome by dynamic nuclear polarization (DNP). Gd(III) complexes are attractive exogenous polarizing agents for magic angle spinning (MAS) DNP due to their high chemical stability in contrast to nitroxide-based radicals. However, even the state-of-the-art Gd(III) complexes have so far provided relatively low DNP signal enhancements of ca. 36 in comparison to standard DNP biradicals, which show enhancements of over 200. Here, we report a series of new Gd(III) complexes for DNP and show that the observed DNP enhancements of the new and existing Gd(III) complexes are inversely proportional to the square of the zero-field splitting (ZFS) parameter D, which is in turn determined by the ligand-type and the local coordination environment. The experimental DNP enhancements at 9.4 T and the ZFS parameters measured with pulsed electron paramagnetic resonance (EPR) spectroscopy agree with the above model, paving the way for the development of more efficient Gd(III) polarizing agents.