Cocrystalline Matrices for Hyperpolarization at Room Temperature Using Photoexcited Electrons.

We propose using cocrystals as effective polarization matrices for triplet dynamic nuclear polarization (DNP) at room temperature. The polarization source can be uniformly doped into cocrystals formed through acid-acid, amide-amide, and acid-amide synthons. The dense-packing crystal structures, facilitated by multiple hydrogen bonding and π-π interactions, result in extended T1 relaxation times, enabling efficient polarization diffusion within the crystals. Our study demonstrates the successful polarization of a DNP-magnetic resonance imaging molecular probe, such as urea, within a cocrystal matrix at room temperature using triplet-DNP.

Hyperpolarization of Biomolecules in Eutectic Crystals at Room Temperature Using Photoexcited Electrons.

The hyperpolarization of biomolecules at room temperature could facilitate highly sensitive magnetic resonance imaging for metabolic studies and nuclear magnetic resonance (NMR)-based screenings for drug discovery. In this study, we demonstrate the hyperpolarization of biomolecules in eutectic crystals using photoexcited triplet electrons at room temperature. Eutectic crystals composed of the domains of benzoic acid doped with the polarization source and analyte domains were prepared using a melting-quenching process. Spin diffusion between the benzoic acid and analyte domain was elucidated using solid-state NMR analysis, indicating that hyperpolarization was transferred from the domain of benzoic acid to the domain of the analyte.

Triplet-DNP in magnetically oriented microcrystal arrays.

We explore dynamic nuclear polarization using electron spins in the photo-excited triplet state (Triplet-DNP) in magnetically oriented microcrystal arrays (MOMAs) of pentacene-doped p-terphenyl, in which the individual crystallites are magnetically aligned and UV-cured. In contrast to the conventional approach to Triplet-DNP in powder, which suffers from reduced nuclear polarization due to the averaged electron polarization and the broadening of electron-spin resonance, Triplet-DNP of the MOMAs offers as high dynamic polarization as that attainable in single-crystals. In the case of pentacene-doped p-terphenyl, the enhanced 1H polarization in the one-dimensional MOMA, prepared simply by leaving the suspension in a stationary magnetic field before UV curation, can be higher than that attainable in the powder sample by an order of magnitude and comparable to that in single crystals and in the three-dimensional MOMA made using a modulational rotating field. Triplet-DNP of the MOMAs may find potential applications, such as the polarization of the co-doped target molecules and dissolution experiments.

Real-time monitoring of enzyme-catalyzed phosphoribosylation of anti-influenza prodrug favipiravir by time-lapse nuclear magnetic resonance spectroscopy.

Favipiravir (brand name Avigan), a widely known anti-influenza prodrug, is metabolized by endogenous enzymes of host cells to generate the active form, which exerts inhibition of viral RNA-dependent RNA polymerase activity; first, favipiravir is converted to its phosphoribosylated form, favipiravir-ribofuranosyl-5'-monophosphate (favipiravir-RMP), by hypoxanthine-guanine phosphoribosyltransferase (HGPRT). Because this phosphoribosylation reaction is the rate-determining step in the generation of the active metabolite, quantitative and real-time monitoring of the HGPRT-catalyzed reaction is essential to understanding the pharmacokinetics of favipiravir. However, assay methods enabling such monitoring have not been established. 19 F- or 31 P-based nuclear magnetic resonance (NMR) are powerful techniques for observation of intermolecular interactions, chemical reactions, and metabolism of molecules of interest, given that NMR signals of the heteronuclei sensitively reflect changes in the chemical environment of these moieties. Here, we demonstrated direct, sensitive, target-selective, nondestructive, and real-time observation of HGPRT-catalyzed conversion of favipiravir to favipiravir-RMP by performing time-lapse 19 F-NMR monitoring of the fluorine atom of favipiravir. In addition, we showed that 31 P-NMR can be used for real-time observation of the identical reaction by monitoring phosphorus atoms of the phosphoribosyl group of favipiravir-RMP and of the pyrophosphate product of that reaction. Furthermore, we demonstrated that NMR approaches permit the determination of general parameters of enzymatic activity such as Vmax and Km . This method not only can be widely employed in enzyme assays, but also may be of use in the screening and development of new favipiravir-analog antiviral prodrugs that can be phosphoribosylated more efficiently by HGPRT, which would increase the intracellular concentration of the drug's active form. The techniques demonstrated in this study would allow more detailed investigation of the pharmacokinetics of fluorinated drugs, and might significantly contribute to opening new avenues for widespread pharmaceutical studies.

Room-temperature hyperpolarization of polycrystalline samples with optically polarized triplet electrons: pentacene or nitrogen-vacancy center in diamond?

We demonstrate room-temperature 13C hyperpolarization by dynamic nuclear polarization (DNP) using optically polarized triplet electron spins in two polycrystalline systems: pentacene-doped [carboxyl-13C] benzoic acid and microdiamonds containing nitrogen-vacancy (NV-) centers. For both samples, the integrated solid effect (ISE) is used to polarize the 13C spin system in magnetic fields of 350-400 mT. In the benzoic acid sample, the 13C spin polarization is enhanced by up to 0.12 % through direct electron-to-13C polarization transfer without performing dynamic 1H polarization followed by 1H-13C cross-polarization. In addition, the ISE has been successfully applied to polarize naturally abundant 13C spins in a microdiamond sample to 0.01 %. To characterize the buildup of the 13C polarization, we discuss the efficiencies of direct polarization transfer between the electron and 13C spins as well as that of 13C-13C spin diffusion, examining various parameters which are beneficial or detrimental for successful bulk dynamic 13C polarization.

High-field NMR with dissolution triplet-DNP.

Dissolution dynamic nuclear polarization (DNP) has wide variety of important applications such as real-time monitoring of chemical reactions and metabolic imaging. We construct DNP using photoexcited triplet electron spins (Triplet-DNP) apparatus combined with dissolution apparatus for solution NMR in a high magnetic field. Triplet-DNP enables us to obtain high nuclear polarization at room temperature. Solid-state samples polarized by Triplet-DNP are transferred to a superconducting magnet and dissolved by injecting aqueous solvents. The 13C polarization of 0.22% has been obtained for [caryboxy-13C]benzoic acid-d in the liquid state. Our results show that Triplet-DNP can be applied to real-time monitoring with solution NMR.

Dynamic nuclear polarization with photo-excited triplet electrons using 6,13-diphenylpentacene.

Dynamic nuclear polarization with photo-excited triplet electrons (Triplet-DNP) is demonstrated using 6,13-diphenylpentacene (DPPentacene). DPPentacene is soluble in various organic solvents, while pentacene, which is used in most of the triplet-DNP experiments, has limited solubility. An enhancement factor of 81 is obtained for 1H spins in the glass of ethanol-d6 : water = 80 : 20 (w/w) doped with 0.1 mM DPPentacene at 90 K in 0.67 T.

Dynamic Nuclear Polarization using Photoexcited Triplet Electron Spins in Eutectic Mixtures.

Dynamic nuclear polarization using photoexcited triplet electrons (Triplet-DNP) is a method to significantly enhance nuclear spin polarization even in a low magnetic field and at room temperature. Pentacene has been practically used as an efficient polarizing agent for Triplet-DNP. In this study, we demonstrate room temperature 1H and 13C hyperpolarization of eutectic mixtures of deuterated benzoic acid doped with pentacene and a target molecule such as salicylic acid, nicotinic acid, or 2-naphthoic acid. These molecules are otherwise difficult to hyperpolarize by Triplet-DNP due to the low pentacene dopabilities of these molecules. The highest 1H polarization of 1.2% has been obtained for the eutectic mixture of salicylic acid in 0.39 T. The present sample preparation is a crucial method to widen the range of applications of Triplet-DNP to chemical and biomedical analyses.

Dissolution Dynamic Nuclear Polarization at Room Temperature Using Photoexcited Triplet Electrons.

Dissolution dynamic nuclear polarization (DNP) has recently gained attention as a method to enhance the sensitivity of liquid NMR spectroscopy and MRI. We demonstrate dissolution of the sample hyperpolarized by DNP using photoexcited triplet electrons in 0.38 T at room temperature. The achieved polarization of 0.8% is 6100 times as high as that at thermal equilibrium under the condition. The result is an important step for DNP using photoexcited triplet electrons to become widely used in chemical and biomedical research.

A Ku band pulsed electron paramagnetic resonance spectrometer using an arbitrary waveform generator for quantum control experiments at millikelvin temperatures.

We present a 17 GHz (Ku band) arbitrary waveform pulsed electron paramagnetic resonance spectrometer for experiments down to millikelvin temperatures. The spectrometer is located at room temperature, while the resonator is placed either in a room temperature magnet or inside a cryogen-free dilution refrigerator; the operating temperature range of the dilution unit is from ca. 10 mK to 8 K. This combination provides the opportunity to perform quantum control experiments on electron spins in the pure-state regime. At 0.6 T, spin echo experiments were carried out using γ-irradiated quartz glass from 1 K to 12.3 mK. With decreasing temperatures, we observed an increase in spin echo signal intensities due to increasing spin polarizations, in accordance with theoretical predictions. Through experimental data fitting, thermal spin polarization at 100 mK was estimated to be at least 99%, which was almost pure state. Next, to demonstrate the ability to create arbitrary waveform pulses, we generate a shaped pulse by superposing three Gaussian pulses of different frequencies. The resulting pulse was able to selectively and coherently excite three different spin packets simultaneously-a useful ability for analyzing multi-spin system and for controlling a multi-qubit quantum computer. By applying this pulse to the inhomogeneously broadened sample, we obtain three well-resolved excitations at 8 K, 1 K, and 14 mK.

Room temperature hyperpolarization of nuclear spins in bulk.

Dynamic nuclear polarization (DNP), a means of transferring spin polarization from electrons to nuclei, can enhance the nuclear spin polarization (hence the NMR sensitivity) in bulk materials at most 660 times for (1)H spins, using electron spins in thermal equilibrium as polarizing agents. By using electron spins in photo-excited triplet states instead, DNP can overcome the above limit. We demonstrate a (1)H spin polarization of 34%, which gives an enhancement factor of 250,000 in 0.40 T, while maintaining a bulk sample (∼ 0.6 mg, ∼ 0.7 × 0.7 × 1 mm(3)) containing >10(19) (1)H spins at room temperature. Room temperature hyperpolarization achieved with DNP using photo-excited triplet electrons has potentials to be applied to a wide range of fields, including NMR spectroscopy and MRI as well as fundamental physics.

Strongly driven electron spins using a K(u) band stripline electron paramagnetic resonance resonator.

This article details our work to obtain strong excitation for electron paramagnetic resonance (EPR) experiments by improving the resonator's efficiency. The advantages and application of strong excitation are discussed. Two 17 GHz transmission-type, stripline resonators were designed, simulated and fabricated. Scattering parameter measurements were carried out and quality factor were measured to be around 160 and 85. Simulation results of the microwave's magnetic field distribution are also presented. To determine the excitation field at the sample, nutation experiments were carried out and power dependence were measured using two organic samples at room temperature. The highest recorded Rabi frequency was rated at 210 MHz with an input power of about 1 W, which corresponds to a π/2 pulse of about 1.2 ns.

Scalable spin amplification with a gain over a hundred.

We propose a scalable and practical implementation of spin amplification which does not require individual addressing nor a specially tailored spin network. We have demonstrated a gain of 140 in a solid-state nuclear spin system of which the spin polarization has been increased to 0.12 using dynamic nuclear polarization with photoexcited triplet electron spins. Spin amplification scalable to a higher gain opens the door to the single spin measurement for a readout of quantum computers as well as practical applications of nuclear magnetic resonance spectroscopy to infinitesimal samples which have been concealed by thermal noise.

Magnetic-field cycling instrumentation for dynamic nuclear polarization-nuclear magnetic resonance using photoexcited triplets.

To advance static solid-state NMR with hyperpolarized nuclear spins, a system has been developed enabling dynamic nuclear polarization (DNP) using electron spins in the photoexcited triplet state with X-band microwave apparatus, followed by static solid-state nuclear magnetic resonance (NMR) experiments using the polarized nuclear-spin system with a goniometer. In order to perform the DNP and NMR procedures in different magnetic fields, the DNP system and the NMR system are spatially separated, between which the sample can be shuttled while its orientation is controlled in a reproducible fashion. We demonstrate that the system developed in this work is operational for solid-state NMR with hyperpolarized nuclear-spin systems in static organic materials, and also discuss the application of our system.

Optimization of 1H spin density for dynamic nuclear polarization using photo-excited triplet electron spins.

In dynamic nuclear polarization (DNP) using photo-excited triplet electron spins, known as Microwave-Induced Optical Nuclear Polarization (MIONP), the attainable (1)H polarization is determined by the ratio of the buildup rate and the spin-lattice relaxation rate, in turn depend on the (1)H spin density. It is shown that the final (1)H polarization can be enhanced by diluting the (1)H spins with partial deuteration. The DNP experiments are demonstrated in 0.05 mol% pentacene-doped p-terphenyl for various (1)H abundances. It is also shown that the (1)H spin diffusion coefficient can be determined by examining the initial buildup rate of (1)H polarization for various repetition rates of the DNP sequence.

Enhancement of efficiency in photo-excitation to the triplet state by laser-pulse reshaping.

An optical system is proposed to enhance efficiency in photo-excitation to the triplet state by reshaping an original laser pulse into a train of pulses. This optical system can be used to improve the attainable nuclear spin polarization in dynamic nuclear polarization experiments using photo-excited triplet electron spins.