Dynamic Nuclear Polarization Effect Research Articles

Red Shift in the Absorption Spectrum of Phototropin LOV1 upon the Formation of a Semiquinone Radical: Reconstructing the Orbital Architecture.

Flavin mononucleotide (FMN) is a ubiquitous blue-light pigment due to its ability to drive one- and two-electron transfer reactions. In both light-oxygen-voltage (LOV) domains of phototropin from the green algae Chlamydomonas reinhardtii, FMN is noncovalently bound. In the LOV1 cysteine-to-serine mutant (C57S), light-induced electron transfer from a nearby tryptophan occurs, and a transient spin-correlated radical pair (SCRP) is formed. Within this photocycle, nuclear hyperpolarization is created by the solid-state photochemically induced dynamic nuclear polarization (photo-CIDNP) effect. In a side reaction, a stable protonated semiquinone radical (FMNH·) forms undergoing a significant bathochromic shift of the first electronic transition from 445 to 591 nm. The incorporation of phototropin LOV1-C57S into an amorphous trehalose matrix, stabilizing the radical, allows for application of various magnetic resonance experiments at ambient temperatures, which are combined with quantum-chemical calculations. As a result, the bathochromic shift of the first absorption band is explained by lifting the degeneracy of the molecular orbital energy levels for electrons with alpha and beta spins in FMNH· due to the additional electron.

Probing Homogeneous Catalysts and Precatalysts in Solution by Exchange-Mediated Overhauser Dynamic Nuclear Polarization NMR.

Triphenylphosphine (PPh3) is a ubiquitous ligand in organometallic chemistry that has been shown to give enhanced 31P NMR signals at high magnetic field via a scalar-dominated Overhauser effect dynamic nuclear polarization (OE DNP). However, PPh3 can only be polarized via DNP in the free form, while the coordinated form is DNP-inactive. Here, we demonstrate the possibility of enhancing the 31P NMR signals of coordinated PPh3 in metal complexes in solution at room temperature by combining Overhauser effect DNP and chemical exchange between the free and coordinated PPh3 forms. With this method, we successfully obtain 31P DNP enhancements of up to 2 orders of magnitude for the PPh3 ligands in Rh(I), Ru(II), Pd(II), and Pt(II) complexes, and we show that the DNP enhancements can be used to determine the activation energy of the ligand exchange reaction.

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.

Multi Electron Spin Cluster Enabled Dynamic Nuclear Polarization with Sulfonated BDPA.

Dynamic nuclear polarization (DNP) can amplify the solid-state nuclear magnetic resonance (NMR) signal by several orders of magnitude. The mechanism of DNP utilizing α,γ-bisdiphenylene-β-phenylallyl (BDPA) variants as Polarizing Agents (PA) has been the subject of lively discussions on account of their remarkable DNP efficiency with low demand for microwave power. We propose that electron spin clustering of sulfonated BDPA is responsible for its DNP performance, as revealed by the temperature-dependent shape of the central DNP profile and strong electron-electron (e-e) crosstalk seen by Electron Double Resonance. We demonstrate that a multielectron spin cluster can be modeled with three coupled spins, where electron J (exchange) coupling between one of the e-e pairs matching the NMR Larmor frequency induces the experimentally observed absorptive central DNP profile, and the electron T1e modulated by temperature and magic-angle spinning alters the shape between an absorptive and dispersive feature. Understanding the microscopic origin is key to designing new PAs to harness the microwave-power-efficient DNP effect observed with BDPA variants.

Stabilization of a flavoprotein for solid-state photo-CIDNP MAS NMR at room temperature by embedding in a glassy sugar matrix

Hyperpolarization via the solid-state photochemically induced dynamic nuclear polarization (photo-CIDNP) effect can be detected in frozen solutions of electron transfer proteins generating a radical-pair upon illumination. The effect has been observed in various natural photosynthetic reaction centers and in light-oxygen-voltage (LOV) sensing domains incorporating a flavin mononucleotide (FMN) as chromophore. In LOV domains, where a highly conserved cysteine is mutated to a flavin to interrupt its natural photochemistry, a radical-pair is generated by electron transfer from a nearby tryptophan to the photoexcited triplet state of FMN. During the photocycle, both the LOV domain and the chromophore are photochemically degraded, e.g., by the formation of singlet oxygen. This limits the time for collection of hyperpolarized nuclear magnetic resonance (NMR) data. We show that embedding of the protein into a trehalose sugar glass matrix stabilizes the protein for 13C solid-state photo-CIDNP NMR experiments which can be conducted at room temperature in a powder sample. Additionally, this preparation allows for incorporation of high amounts of protein further boosting the intensity of the detected signals from FMN and tryptophan at natural abundance. Signal assignment is aided by quantum chemical calculations of absolute shieldings. The underlying mechanism for the surprising absorption-only signal pattern is not yet understood. Comparison to calculated isotropic hyperfine couplings imply that the enhancement is not due to the classical radical-pair mechanism (RPM). Analysis of the anisotropic hyperfine couplings associated with solid-state photo-CIDNP mechanisms also show no simple correlation, suggesting a more complex underlying mechanism.

An EPR Study on Highly Stable Nitroxyl-Nitroxyl Biradicals for Dynamic Nuclear Polarization Applications at High Magnetic Fields.

Nitroxide biradicals are efficient polarizing agents in dynamic nuclear polarization (DNP) solid-state nuclear magnetic resonance. Many recently reported radicals possess substantial DNP efficiency in organic solvents but have poor solubility in water media which is unfavorable for biological applications. In this paper, we report DNP efficiency at a high magnetic field for two water-soluble biradicals resistant to reducing media. Water solubility was achieved by obtaining the radicals in the form of quaternary ammonium salts. Parameters of hyperfine interaction and exchange interaction were quantified by EPR spectroscopy, and their influence on the DNP effect was determined. The resistance of the biradicals to strongly reducing media was characterized. High stability was achieved using tetraethyl substituents and pyrrolidine moieties.

Amplified Overhauser DNP with Selective Deuteration: Attenuation of Double-Quantum Cross-Relaxation

We recently used selective 2H labeling of BDPA to investigate the Overhauser Effect (OE) dynamic nuclear polarization (DNP) mechanism in insulating solids doped with 1,3-bis(diphenylene)-2-phenylallyl (BDPA), and established that the α and γ 1H spins on the fluorene rings are responsible for generating a zero quantum (ZQ) mediated positive bulk polarization. Here, we establish that the phenyl 1H spins relax via double-quantum (DQ) processes and therefore contribute negative enhancements which attenuate the OE-DNP. With measurements at different magnetic field strengths, we show that phenyl-d5-BDPA offers >50% improvement in OE-DNP enhancement compared to h21-BDPA attaining a maximum of ∼90 at 14.1 T and 5 kHz MAS, the highest observed OE-DNP enhancement to date under these conditions. The approach may be utilized to optimize other polarizing agents exhibiting an OE, an important DNP mechanism with a favorable field and spinning frequency dependence.

JOM-4S Overhauser Magnetometer and Sensitivity Estimation.

The Overhauser magnetometer is a scalar quantum magnetometer based on the dynamic nuclear polarization (DNP) effect in the Earth’s magnetic field. Sensitivity is a key technical specification reflecting the ability of instruments to sense small variations of the Earth’s magnetic field and is closely related to the signal-to-noise ratio (SNR) of the free induction decay (FID) signal. In this study, deuterated 15N TEMPONE radical is used in our sensor to obtain high DNP enhancement. The measured SNR of the FID signal is approximately 63/1, and the transverse relaxation time T2 is 2.68 s. The direct measurement method with a single instrument and the synchronous measurement method with two instruments are discussed for sensitivity estimation in time and frequency domains under different electromagnetic interference (EMI) environments and different time periods. For the first time, the correlation coefficient of the magnetic field measured by the two instruments is used to judge the degree of the influence of the environmental noise on the sensitivity estimation. The sensitivity evaluation in the field environment is successfully realized without electrical and magnetic shields. The direct measurement method is susceptible to EMI and cannot work in general electromagnetic environments, except it is sufficiently quiet. The synchronous measurement method has an excellent ability to remove most natural and artificial EMIs and can be used under noisy environments. Direct and synchronous experimental results show that the estimated sensitivity of the JOM-4S magnetometer is approximately 0.01 nT in time domain and approximately 0.01 nT/ in frequency domain at a 3 s cycling time. This study provides a low-cost, simple, and effective sensitivity estimation method, which is especially suitable for developers and users to estimate the performance of the instrument.

Spin Temperature and Dynamic Nuclear Polarization. From the History of Researches (1953 – 1983)

An attempt is proposed in the most concise form to provide the reader with a history of research and applications of dynamic nuclear polarization (DNP). The main attention is paid to the first three decades of DNP research, and the history of the discovery and development of multiparticle DNP and its relationship with the spin temperature approximation are outlined in some detail. The article emphasizes the role of such researchers as Anatol Abraham, Maurice Goldman, Michel Borghini, Thomas Wenckebach, Vadim Atsarkin, Boris Provotorov, Maya Rodak, Mortko Kozhushner, Levan Buishvili, Givi Khutsishvili. As far as possible, the contributions of many other scientists are considered. The establishment of a uniform temperature for nuclear spins due to the effect of spin diffusion was first proposed by Nicholas Blombergen in 1949. The content of the article is based on the bibliography available in the public domains, in particular on the memoirs of the research participants, and first of all on the materials of Atsarkin's 1978 review in Sov. Phys. Uspekhi and on the oral history of the development of the multiparticle concept of DNP effects, recorded from the speeches of the participants of the Moscow seminar "Problems of Magnetic Resonance" in 2001. A simplified description of the effects of DNP and a summary of the history of their discovery is given in section “Introduction”. The shortest biographical data and portraits of participants in the DNP study are given in Appendix 1, and a selected bibliography on the problems of DNP and spin temperatures is given in Appendix 2. The bibliography divided into four sections according to the time and type of publication (I - historical research, memoirs; II – monographs, reviews; III - original publications 1953 - 1983; IV – some original publications of a later time, mainly during the transformation of DNP into an method for the implementation of nuclear magnetic spectroscopy and tomography in the interests of chemistry, biochemistry and medicine). The widespread use of DNP methods is evidenced, for example, by the fact, that by now company Bruker BioSpin has installed about 50 gyrotron based spectrometers for DNP operating upto 593 GHz worldwide to date.

Molecular Dynamics and Proton Hyperpolarization via Synthetic and Crude Oil Porphyrin Complexes in Solid and Solution States.

The use of vanadyl porphyrins either in synthetic compounds or naturally occurring in asphaltenes is investigated as a source of proton hyperpolarization via dynamic nuclear polarization (DNP) in nuclear magnetic resonance (NMR) experiments. The features of dynamics and location of the vanadyl VO2+ complex in aggregates within the oil asphaltene molecules are studied by means of DNP, electron paramagnetic resonance (EPR), and NMR field cycling relaxometry. Both the solid effect and Overhauser DNP were observed for the asphaltene solution in benzene, as well as in the solution and solid states for synthetic compounds. By comparison with a solution of synthetic vanadyl porphyrins, it is shown that vanadyl porphyrins in asphaltene aggregates are localized outside of the interface of the asphaltene aggregates and more exposed to the maltene molecules than "free" carbon-centered radicals associated with the core of asphaltene molecules. The perceptible contribution of scalar interaction is observed in solutions for both synthetic and asphaltene vanadyl porphyrins.

Organic Mixed-Valence Compounds and the Overhauser Effect in Insulating Solids.

Recent experiments have shown that the organic free radical 1,3-bisdiphenylene-2-phenylallyl (BDPA) can induce an Overhauser effect dynamic nuclear polarization in insulating solids, a feat previously considered not to be possible. Here, we establish that this peculiar ability of the BDPA radical stems from its mixed-valence nature and the ensuing intramolecular charge transfer. Using state-of-the-art DMRGSCF calculations, we confirm the class II mixed-valence nature of BDPA with the characteristic double-well potential energy surface, and we investigate the mechanism of the consequent electron hopping. A two-component vibronic Hamiltonian is then employed to compute the rate of electron hopping from a quantum dynamical time-propagation of the density matrix. The predicted hyperfine coupling oscillations indeed fall within the frequency range required for an Overhauser effect. The paradigm of mixed-valence compounds as a mining source opens many possibilities for the development and fine tuning of novel polarizing agents.

A Magic Angle Spinning Activated 17O DNP Raser.

In the raser effect, a sample spontaneously emits continuous radiofrequency radiation, allowing exceptionally narrow NMR line widths to be recorded without applying pulses. To achieve this phenomenon, a large negative magnetization must be induced, which we show here can be achieved for the 17O magnetization of isotopically labeled Gd-doped CeO2 using solid effect dynamic nuclear polarization (DNP), at high field and 110 K. This allows a 2 mHz line width to be measured, which is limited only by the magnetic field stability. The raser effect can be reversibly activated and deactivated by magic angle spinning (MAS), which modulates the nuclear spin coherence lifetime. The use of MAS DNP to enable the raser effect should be further applicable to other systems and nuclei.

Characterization of photonic band resonators for DNP NMR of thin film samples at 7 T magnetic field

Polarization of nuclear spins via Dynamic Nuclear Polarization (DNP) relies on generating sufficiently high mm-wave B1e fields over the sample, which could be achieved by developing suitable resonance structures. Recently, we have introduced one-dimensional photonic band gap (1D PBG) resonators for DNP and reported on prototype devices operating at ca. 200 GHz electron resonance frequency. Here we systematically compare the performance of five (5) PBG resonators constructed from various alternating dielectric layers by monitoring the DNP effect on natural-abundance 13C spins in synthetic diamond microparticles embedded into a commercial polyester-based lapping film of just 3 mil (76 μm) thickness. An odd-numbered configuration of dielectric layers for 1D PBG resonator was introduced to achieve further B1e enhancements. Among the PBG configurations tested, combinations of high-ε perovskite LiTaO3 together with AlN as well as AlN with optical quartz wafers have resulted in ca. 40 to over 50- fold gains in the average mm-wave power over the sample vs. the mirror-only configuration. The results are rationalized in terms of the electromagnetic energy distribution inside the resonators obtained analytically and from COMSOL simulations. It was found that average of B1e2 over the sample strongly depends on the arrangement of the dielectric layers that are the closest to the sample, which favors odd-numbered PBG resonator configurations for their use in DNP.

Dynamic Nuclear Polarization with Vanadium(IV) Metal Centers

Summary Dynamic nuclear polarization (DNP) harnesses the large polarization of electron spins to dramatically increase nuclear magnetic resonance (NMR) sensitivity. This study expands the scope of DNP beyond its traditional focus on hyperpolarizing the solvent network using exogenous polarizing agents (PAs). We introduce 1H DNP with endogenous V4+ centers positioned in a set of vanadyl complexes with tunable V4+-1H distances. We traced the polarization transfer from V4+ to 1H spins, specifically differentiating between direct V4+-1Hs polarization transfer and the 1H spin-diffusion-mediated bulk solvent 1H polarization buildup and illuminated the effect of the V4+-1H distance on these processes. These results deepen our understanding of polarization pathways and expand the catalog of PAs to broad-line transition metals. This study establishes crucial first steps toward employing strategically positioned endogenous paramagnetic metal centers for DNP and the conceptual framework of hyperfine DNP spectroscopy that merges both spatial and chemical diagnosis of target nuclear spins.

Tailored flavoproteins acting as light-driven spin machines pump nuclear hyperpolarization

The solid-state photo-chemically induced dynamic nuclear polarization (photo-CIDNP) effect generates non-Boltzmann nuclear spin magnetization, referred to as hyperpolarization, allowing for high gain of sensitivity in nuclear magnetic resonance (NMR). Well known to occur in photosynthetic reaction centers, the effect was also observed in a light-oxygen-voltage (LOV) domain of the blue-light receptor phototropin, in which the functional cysteine was removed to prevent photo-chemical reactions with the cofactor, a flavin mononucleotide (FMN). Upon illumination, the FMN abstracts an electron from a tryptophan to form a transient spin-correlated radical pair (SCRP) generating the photo-CIDNP effect. Here, we report on designed molecular spin-machines producing nuclear hyperpolarization upon illumination: a LOV domain of aureochrome1a from Phaeodactylum tricornutum, and a LOV domain named 4511 from Methylobacterium radiotolerans (Mr4511) which lacks an otherwise conserved tryptophan in its wild-type form. Insertion of the tryptophan at canonical and novel positions in Mr4511 yields photo-CIDNP effects observed by 15N and 1H liquid-state high-resolution NMR with a characteristic magnetic-field dependence indicating an involvement of anisotropic magnetic interactions and a slow-motion regime in the transient paramagnetic state. The heuristic biomimetic design opens new categories of experiments to analyze and apply the photo-CIDNP effect.

1H Thermal Mixing Dynamic Nuclear Polarization with BDPA as Polarizing Agents.

Dynamic Nuclear Polarization (DNP) is a sensitivity enhancing technique for Nuclear Magnetic Resonance. A recent discovery of Overhauser Effect (OE) DNP in insulating systems under cryogenic conditions using 1,3-bisdiphenylene-2-phenylallyl (BDPA) as the polarizing agent (PA) has caught attention due to its promising DNP performance at a high magnetic field and under fast magic angle spinning conditions. However, the mechanism of OE in insulating-solids/BDPA is unclear. We present an alternative explanation that the dominant underlying DNP mechanism of BDPA is Thermal Mixing (TM). This is ascertained with the discovery that TM effect is enhanced by multi-electron spin coupling, which is corroborated by an asymmetric electron paramagnetic resonance line shape signifying the coexistence of clustered and isolated BDPA species, and by hyperpolarized electron spin populations giving rise to an electron spin polarization gradient which are characteristic signatures of TM DNP. Finally, quantum mechanical simulations using spatially asymmetrically coupled three electron spins and a nuclear spin demonstrate that triple-flip DNP, with hyperfine fluctuations turned off, can yield the 1H DNP profile as observed with BDPA. Clarifying the DNP mechanism is critical to develop design principles for optimizing the PA for achieving optimal DNP efficiency.

Remarkable Mechanism of the Reaction between Mixed Phosphonium-Iodonium Ylides and Acetylenes

Reactions of mixed phosphonium-iodonium ylides with nitriles and acetylenes allow for the synthesis of not easily accessible and novel heterocyclic compounds in a simple, one-pot, metal-free system. The results of the mechanistic investigation of the reaction of the phosphonium-iodonium ylides with acetylenes by means of spectrophotometry, EPR and NMR spectroscopy are discussed in this review. This investigation allows to account for unusual regularities of these reactions: induction time, acid catalysis, chemically induced dynamic nuclear polarization effect (CIDNP) observed in several systems, and others. The radical character of the initiation of the reaction as a result of acid catalysis of the ylides decomposition on radicals and the participation of radical intermediates in the formation of all target products have been unambiguously established. The mechanism of generation of radical pairs in CIDNP was suggested, and the role of microheterogeniety of the ylide solutions in methylene chloride was substantiated. On the basis of the study of the reaction mechanism, the conditions for the increase in the yields of new heterocyclic compounds can be optimized.

Characterization of frequency-chirped dynamic nuclear polarization in rotating solids

Continuous wave (CW) dynamic nuclear polarization (DNP) is used with magic angle spinning (MAS) to enhance the typically poor sensitivity of nuclear magnetic resonance (NMR) by orders of magnitude. In a recent publication we show that further enhancement is obtained by using a frequency-agile gyrotron to chirp incident microwave frequency through the electron resonance frequency during DNP transfer. Here we characterize the effect of chirped MAS DNP by investigating the sweep time, sweep width, center-frequency, and electron Rabi frequency of the chirps. We show the advantages of chirped DNP with a trityl-nitroxide biradical, and a lack of improvement with chirped DNP using AMUPol, a nitroxide biradical. Frequency-chirped DNP on a model system of urea in a cryoprotecting matrix yields an enhancement of 142, 21% greater than that obtained with CW DNP. We then go beyond this model system and apply chirped DNP to intact human cells. In human Jurkat cells, frequency-chirped DNP improves enhancement by 24% over CW DNP. The characterization of the chirped DNP effect reveals instrument limitations on sweep time and sweep width, promising even greater increases in sensitivity with further technology development. These improvements in gyrotron technology, frequency-agile methods, and in-cell applications are expected to play a significant role in the advancement of MAS DNP.

Optically-generated Overhauser dynamic nuclear polarization: A numerical analysis.

Recently, an alternative approach to dynamic nuclear polarization (DNP) in the liquid state was introduced using optical illumination instead of microwave pumping. By exciting a suitable dye to the triplet state which undergoes a diffusive encounter with a persistent radical forming a quartet-doublet pair in the encounter complex, dynamic electron polarization (DEP) is generated via the radical-triplet pair mechanism. Subsequent cross-relaxation generates nuclear polarization without the need for microwave saturation of the electronic transitions. Here, we present a theoretical justification for the initial experimental results by means of numerical simulations. These allow investigation of the effects of various experimental parameters, such as radical and dye concentrations, sample geometry, and laser power, on the DNP enhancement factors, providing targets for experimental optimization. It is predicted that reducing the sample volume will result in larger enhancements by permitting a higher concentration of triplets in a sample of increased optical density. We also explore the effects of the pulsed laser rather than continuous-wave illumination, rationalizing the failure to observe the optical DNP effect under illumination conditions common to DEP experiments. Examining the influence of the illumination duty cycle, the conditions necessary to permit the use of pulsed illumination without compromising signal enhancement are determined, which may reduce undesirable laser heating effects. This first simulation of the optical DNP method therefore underpins the further development of the technology.

Balancing dipolar and exchange coupling in biradicals to maximize cross effect dynamic nuclear polarization.

Dynamic nuclear polarization (DNP) by the cross effect (CE) has become a game changer for solid-state nuclear magnetic resonance (NMR) spectroscopy. The efficiency of CE-DNP depends on the strength of the electron-electron coupling in biradical polarizing agents. Hence, the focus lately has been on designing biradicals with a large net exchange (J) and dipolar (D) coupling. In this study, we reveal that the crucial factor for CE-DNP is not the large sum, J + D, but rather the relative magnitude of J and D, expressed as the J/D ratio. We show that the mechanistic basis of this interference lies in the isotropic vs. the anisotropic nature of the J and D couplings, respectively. This interference can lead to a small (effective) electron-electron coupling for many orientations even when J + D is large, resulting in non-adiabatic rotor-events. We find that when 0 < |J/D| < 1 the CE-DNP efficiency is attenuated for the majority of orientations, with greater attenuation observed at higher magnetic fields and faster magic-angle spinning (MAS) frequency. The interference effect of J and D coupling introduced in this study can explain why many biradicals with high or comparable J + D still show significantly divergent DNP performances. We debut J/D as a consequential criteria for designing efficient biradicals to robustly perform across a large range of B0 fields and MAS frequencies.