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NMR hyperpolarization techniques enhance nuclear spin polarization by several orders of magnitude resulting in corresponding sensitivity gains. This enormous sensitivity gain enables new applications ranging from studies of small molecules by using high-resolution NMR spectroscopy to real-time metabolic imaging in vivo. Several hyperpolarization techniques exist for hyperpolarization of a large repertoire of nuclear spins, although the 13 C and 15 N sites of biocompatible agents are the key targets due to their widespread use in biochemical pathways. Moreover, their long T1 allows hyperpolarized states to be retained for up to tens of minutes. Signal amplification by reversible exchange (SABRE) is a low-cost and ultrafast hyperpolarization technique that has been shown to be versatile for the hyperpolarization of 15 N nuclei. Although large sensitivity gains are enabled by hyperpolarization, 15 N natural abundance is only ∼0.4 %, so isotopic labeling of the molecules to be hyperpolarized is required in order to take full advantage of the hyperpolarized state. Herein, we describe selected advances in the preparation of 15 N-labeled compounds with the primary emphasis on using these compounds for SABRE polarization in microtesla magnetic fields through spontaneous polarization transfer from parahydrogen. Also, these principles can certainly be applied for hyperpolarization of these emerging contrast agents using dynamic nuclear polarization and other techniques.

Signal Amplification by Reversible Exchange (SABRE) is a promising method for NMR signal enhancement and production of hyperpolarized molecules. As nuclear spin relaxation times of heteronuclei are usually much longer than those of protons, SABRE-based hyperpolarization of heteronuclei in molecules is highly important in the context of biomedical applications. In this work, we demonstrate that the SLIC-SABRE technique can be successfully used to hyperpolarize 15 N nuclei in dalfampridine. The high polarization level of ca. 8 % achieved in this work made it possible to acquire 15 N MR images at natural abundance of the 15 N nuclei for the first time.

The NMR hyperpolarization of uniformly 15 N-labeled [15 N3 ]metronidazole is demonstrated by using SABRE-SHEATH. In this antibiotic, the 15 NO2 group is hyperpolarized through spin relays created by 15 N spins in [15 N3 ]metronidazole, and the polarization is transferred from parahydrogen-derived hydrides over six chemical bonds. In less than a minute of parahydrogen bubbling at approximately 0.4 μT, a high level of nuclear spin polarization (P15N ) of around 16 % is achieved on all three 15 N sites. This product of 15 N polarization and concentration of 15 N spins is around six-fold better than any previous value determined for 15 N SABRE-derived hyperpolarization. At 1.4 T, the hyperpolarized state persists for tens of minutes (relaxation time, T1 ≈10 min). A novel synthesis of uniformly 15 N-enriched metronidazole is reported with a yield of 15 %. This approach can potentially be used for synthesis of a wide variety of in vivo metabolic probes with potential uses ranging from hypoxia sensing to theranostic imaging.

Magnetic Resonance Imaging (MRI) is a powerful non-invasive diagnostic method extensively used in biomedical studies. A significant limitation of MRI is its relatively low signal-to-noise ratio, which can be increased by hyperpolarizing nuclear spins. One promising method is Signal Amplification By Reversible Exchange (SABRE), which employs parahydrogen as a source of hyperpolarization. Recent studies demonstrated the feasibility to improve MRI sensitivity with this hyperpolarization technique. Hyperpolarized (15)N nuclei in biomolecules can potentially retain their spin alignment for tens of minutes, providing an extended time window for the utilization of the hyperpolarized compounds. In this work, we demonstrate for the first time that radio-frequency-based SABRE hyperpolarization techniques can be used to obtain (15)N MRI of biomolecule 1-(15)N-nicotinamide. Two image acquisition strategies were utilized and compared: Single Point Imaging (SPI) and Fast Low Angle SHot (FLASH). These methods demonstrated opportunities of high-field SABRE for biomedical applications.

Microreactors attract a significant interest for chemical synthesis due to the benefits of small scales such as high surface to volume ratio, rapid thermal ramping, and well-understood laminar flows. The suitability of atomic layer deposition for application of both the nanoparticle catalyst and the support material on the surfaces of channels of microfabricated silicon microreactors is demonstrated in this research. Continuous-flow hydrogenation of propene into propane at low temperatures with TiO2-supported catalytic Pt nanoparticles was used as a model reaction. Reaction yield and mass transport were monitored by high-sensitivity microcoil NMR spectroscopy as well as time-of-flight remote detection NMR imaging. The microreactors were shown to be very efficient in propene conversion into propane. The yield of 100 % was achieved at 508 C with a reactor decorated with Pt nanoparticles of average size of roughly 1 nm and surface coverage of 3.2 % in 20 mm long reaction channels with a residence time of 1100ms. The activity of the Pt catalyst surfaces was on the order of several to tens of mmol s-1m-2.

Supported metal catalyst was designed, characterized and tested for aqueous phase heterogeneous hydrogenation of vinyl acetate with parahydrogen to produce 13C-hyperpolarized ethyl acetate for potential biomedical applications. The Rh/TiO2 catalyst with 23.2 wt% loading produced strong hyperpolarized 13C-enriched ethyl acetate-1-13C detected at 9.4 T. Approximately 14-fold 13C signal enhancement was detected using ~50% parahydrogen gas without taking into account relaxation losses before and after polarization transfer via magnetic field cycling from nascent parahydrogen-derived protons to 13C nuclei. This first observation of 13C PHIP-hyperpolarized products over supported metal catalyst in the aqueous medium opens up new possibilities for production of catalyst-free aqueous solutions of nontoxic hyperpolarized contrast agents for a wide range of biomolecules amenable to Parahydrogen Induced Polarization via Side Arm Hydrogenation (PHIP-SAH) approach.

A highly isolated monoatomic gold catalyst, with single gold atoms dispersed on multiwalled carbon nanotubes (MWCNTs), has been synthesized, characterized, and tested in heterogeneous hydrogenation of 1,3-butadiene and 1-butyne with parahydrogen to maximize the polarization level and the contribution of the pairwise hydrogen addition route. The Au/MWCNTs catalyst was found to be active and efficient in pairwise hydrogen addition and the estimated contributions from the pairwise hydrogen addition route are at least an order of magnitude higher than those for supported metal nanoparticle catalysts. Therefore, the use of the highly isolated monoatomic catalysts is very promising for production of hyperpolarized fluids that can be used for the significant enhancement of NMR signals. A mechanism of 1,3-butadiene hydrogenation with parahydrogen over the highly isolated monoatomic Au/MWCNTs catalyst is also proposed.