Hyperpolarization of Nitrogen‐15 Schiff Bases by Reversible Exchange Catalysis with <i>para</i>‐Hydrogen

Logan, Angus W. J.; Theis, Thomas; Colell, Johannes F. P.; Warren, Warren S.; Malcolmson, Steven J.

doi:10.1002/chem.201602393

Cited by 44 publications

(43 citation statements)

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“…Next, we found that 15 N nuclei in a wide range of Schiff bases (entry 6), which included biologically relevant scaffolds, such as pyridoxal phosphate analogues and retinal with critical roles in visual signaling, hyperpolarize well. 40−42 …”

Section: Results and Discussionmentioning

confidence: 99%

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Generalizing, Extending, and Maximizing Nitrogen-15 Hyperpolarization Induced by Parahydrogen in Reversible Exchange

et al. 2017

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Signal Amplification by Reversible Exchange (SABRE) is a fast and convenient NMR hyperpolarization method that uses cheap and readily available para-hydrogen as a hyperpolarization source. SABRE can hyperpolarize protons and heteronuclei. Here we focus on the heteronuclear variant introduced as SABRE-SHEATH (SABRE in SHield Enables Alignment Transfer to Heteronuclei) and nitrogen-15 targets in particular. We show that 15N-SABRE works more efficiently and on a wider range of substrates than 1H-SABRE, greatly generalizing the SABRE approach. In addition, we show that nitrogen-15 offers significantly extended T1 times of up to 12 minutes. Long T1 times enable higher hyperpolarization levels but also hold the promise of hyperpolarized molecular imaging for several tens of minutes. Detailed characterization and optimization are presented, leading to nitrogen-15 polarization levels in excess of 10% on several compounds.

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Section: Results and Discussionmentioning

confidence: 99%

“…The presented results suggest that sp and sp 2 hybridized nitrogens can be hyperpolarized, and 15 N polarization of at least several percent can be obtained easily and rapidly (30 s to 1 min) if no impeding factors such as steric hindrance or proton exchange inhibit polarization buildup. 42,48,72 …”

Section: Discussionmentioning

confidence: 99%

Generalizing, Extending, and Maximizing Nitrogen-15 Hyperpolarization Induced by Parahydrogen in Reversible Exchange

et al. 2017

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“…In the context of potential biomedical applications, several classes of nitrogen (sp 2 hybridized) containing compounds, such as pyridine and its derivatives, [46, 50, 88–89] imidazole and its analogs, [39f, 39i, 90] nicotinamide, [39g, 46, 48, 91] various nitriles [39d] and other sp 2 nitrogen containing species [39e, 39j, 92] were hyperpolarized effectively by forming SABRE-enabling complexes in which their molecules were permanently attached in axial positions (Figure 6B). …”

Section: How To Make It Work: the Hyperpolarizer And Chemistry Of mentioning

confidence: 99%

Parahydrogen‐Based Hyperpolarization for Biomedicine

et al. 2018

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Magnetic resonance (MR) is one of the most versatile and useful physical effects used for human imaging, chemical analysis, and the elucidation of molecular structures. However, its full potential is rarely used, because only a small fraction of the nuclear spin ensemble is polarized, that is, aligned with the applied static magnetic field. Hyperpolarization methods seek other means to increase the polarization and thus the MR signal. A unique source of pure spin order is the entangled singlet spin state of dihydrogen, parahydrogen (pH ), which is inherently stable and long-lived. When brought into contact with another molecule, this "spin order on demand" allows the MR signal to be enhanced by several orders of magnitude. Considerable progress has been made in the past decade in the area of pH -based hyperpolarization techniques for biomedical applications. It is the goal of this Review to provide a selective overview of these developments, covering the areas of spin physics, catalysis, instrumentation, preparation of the contrast agents, and applications.

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“…This route shows great potential for enhancing both analytical NMR and clinical diagnosis in the future (17)(18)(19)(20)(21)(22). SABRE does not change the chemical identity of the agent it hyperpolarizes but equilibrates polarization between p-H 2 and the selected agent through binding to an iridium center (23).…”

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Delivering strong ¹ H nuclear hyperpolarization levels and long magnetic lifetimes through signal amplification by reversible exchange

Rayner

Burns

Olaru

et al. 2017

Proc. Natl. Acad. Sci. U.S.A.

121

207

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Hyperpolarization turns typically weak NMR and MRI responses into strong signals so that ordinarily impractical measurements become possible. The potential to revolutionize analytical NMR and clinical diagnosis through this approach reflect this area's most compelling outcomes. Methods to optimize the low-cost parahydrogen-based approach signal amplification by reversible exchange with studies on a series of biologically relevant nicotinamides and methyl nicotinates are detailed. These procedures involve specific 2 H labeling in both the agent and catalyst and achieve polarization lifetimes of ca. 2 min with 50% polarization in the case of methyl-4,6-d 2 -nicotinate. Because a 1.5-T hospital scanner has an effective 1 H polarization level of just 0.0005% this strategy should result in compressed detection times for chemically discerning measurements that probe disease. To demonstrate this technique's generality, we exemplify further studies on a range of pyridazine, pyrimidine, pyrazine, and isonicotinamide analogs that feature as building blocks in biochemistry and many disease-treating drugs.

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Hyperpolarization of Nitrogen‐15 Schiff Bases by Reversible Exchange Catalysis with para‐Hydrogen

Cited by 44 publications

References 31 publications

Generalizing, Extending, and Maximizing Nitrogen-15 Hyperpolarization Induced by Parahydrogen in Reversible Exchange

Generalizing, Extending, and Maximizing Nitrogen-15 Hyperpolarization Induced by Parahydrogen in Reversible Exchange

Parahydrogen‐Based Hyperpolarization for Biomedicine

Delivering strong ¹ H nuclear hyperpolarization levels and long magnetic lifetimes through signal amplification by reversible exchange

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Hyperpolarization of Nitrogen‐15 Schiff Bases by Reversible Exchange Catalysis with para‐Hydrogen

Cited by 44 publications

References 31 publications

Generalizing, Extending, and Maximizing Nitrogen-15 Hyperpolarization Induced by Parahydrogen in Reversible Exchange

Generalizing, Extending, and Maximizing Nitrogen-15 Hyperpolarization Induced by Parahydrogen in Reversible Exchange

Parahydrogen‐Based Hyperpolarization for Biomedicine

Delivering strong 1 H nuclear hyperpolarization levels and long magnetic lifetimes through signal amplification by reversible exchange

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Delivering strong ¹ H nuclear hyperpolarization levels and long magnetic lifetimes through signal amplification by reversible exchange