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Hyperpolarized orthohydrogen (o‐H₂) is a frequent product of parahydrogen‐based hyperpolarization approaches like signal amplification by reversible exchange (SABRE), where the hyperpolarizedo‐H₂signal is usually absorptive. We describe a novel manifestation of this effect wherein large antiphaseo‐H₂signals are observed, with¹H enhancements up to ≈500‐fold (effective polarizationP_H≈1.6 %). This anomalous effect is attained only when using an intact heterogeneous catalyst constructed using a metal–organic framework (MOF) and is qualitatively independent of substrate nature. This seemingly paradoxical observation is analogous to the “partial negative line” (PNL) effect recently explained in the context of Parahydrogen Induced Polarization (PHIP) by Ivanov and co‐workers. The two‐spin order of theo‐H₂resonance is manifested by a two‐fold higher Rabi frequency, and the lifetime of the antiphase HPo‐H₂resonance is extended by several‐fold.

Demonstration of parahydrogen‐induced polarization effects in hydrogenations catalyzed by heterogeneous catalysts instead of metal complexes in a homogeneous solution has opened an entirely new dimension for parahydrogen‐based research, demonstrating its applicability not only for the production of catalyst‐free hyperpolarized liquids and gases and long‐lived non‐equilibrium spin states for potential biomedical applications, but also for addressing challenges of modern fundamental and industrial catalysis including advanced mechanistic studies of catalytic reactions and operando NMR and MRI of reactors. This essay summarizes the progress achieved in this field by highlighting the research contributed to it by our colleague and friend Kirill V. Kovtunov whose scientific career ended unexpectedly and tragically at the age of 37. His role in this research was certainly crucial, further enhanced by a vast network of his contacts and collaborations at the national and international level.

Signal Amplification By Reversible Exchange in SHield Enabled Alignment Transfer (SABRE‐SHEATH) is investigated to achieve rapid hyperpolarization of¹³C₁spins of [1‐¹³C]pyruvate, using parahydrogen as the source of nuclear spin order. Pyruvate exchange with an iridium polarization transfer complex can be modulated via a sensitive interplay between temperature and co‐ligation of DMSO and H₂O. Order‐unity¹³C (>50 %) polarization of catalyst‐bound [1‐¹³C]pyruvate is achieved in less than 30 s by restricting the chemical exchange of [1‐¹³C]pyruvate at lower temperatures. On the catalyst bound pyruvate, 39 % polarization is measured using a 1.4 T NMR spectrometer, and extrapolated to >50 % at the end of build‐up in situ. The highest measured polarization of a 30‐mM pyruvate sample, including free and bound pyruvate is 13 % when using 20 mM DMSO and 0.5 M water in CD₃OD. Efficient¹³C polarization is also enabled by favorable relaxation dynamics in sub‐microtesla magnetic fields, as indicated by fast polarization buildup rates compared to theT₁spin‐relaxation rates (e. g., ∼0.2 s⁻¹versus ∼0.1 s⁻¹, respectively, for a 6 mM catalyst‐[1‐¹³C]pyruvate sample). Finally, the catalyst‐bound hyperpolarized [1‐¹³C]pyruvate can be released rapidly by cycling the temperature and/or by optimizing the amount of water, paving the way to future biomedical applications of hyperpolarized [1‐¹³C]pyruvate produced via comparatively fast and simple SABRE‐SHEATH‐based approaches.

The role of ligands in rhodium‐ and iridium‐catalyzedParahydrogen Induced Polarization (PHIP) and SABRE (signal amplification by reversible exchange) chemistry has been studied in the benchmark systems, [Rh(diene)(diphos)]⁺and [Ir(NHC)(sub)₃(H)₂]⁺, and shown to have a great impact on the degree of hyperpolarization observed. Here, we examine the role of the flanking moieties in the electron‐rich monoanionic bis(carbene) aryl pincer ligand,^ArCCC (Ar=Dipp, 2,6‐diisopropyl or Mes, 2,4,6‐trimethylphenyl) on the cobalt‐catalyzed PHIP and PHIP‐IE (PHIP via Insertion and Elimination) chemistry that we have previously reported. The mesityl groups were exchanged for diisopropylphenyl groups to generate the (^DippCCC)Co(N₂) catalyst, which resulted in faster hydrogenation and up to 390‐fold¹H signal enhancements, larger than that of the (^MesCCC)Co‐py (py=pyridine) catalyst. Additionally, the synthesis of the (^DippCCC)Rh(N₂) complex is reported and applied towards the hydrogenation of ethyl acrylate withparahydrogen to generate modest signal enhancements of both¹H and¹³C nuclei. Lastly, the generation of two (^MesCCC)Ir complexes is presented and applied towards SABRE and PHIP‐IE chemistry to only yield small¹H signal enhancements of the partially hydrogenated product (PHIP) with no SABRE hyperpolarization.

Hyperpolarization is a technique that can increase nuclear spin polarization with the corresponding gains in nuclear magnetic resonance (NMR) signals by 4–8 orders of magnitude. When this process is applied to biologically relevant samples, the hyperpolarized molecules can be used as exogenous magnetic resonance imaging (MRI) contrast agents. A technique called spin‐exchange optical pumping (SEOP) can be applied to hyperpolarize noble gases such as¹²⁹Xe. Techniques based on hyperpolarized¹²⁹Xe are poised to revolutionize clinical lung imaging, offering a non‐ionizing, high‐contrast alternative to computed tomography (CT) imaging and conventional proton MRI. Moreover, CT and conventional proton MRI report on lung tissue structure but provide little functional information. On the other hand, when a subject breathes hyperpolarized¹²⁹Xe gas, functional lung images reporting on lung ventilation, perfusion and diffusion with 3D readout can be obtained in seconds. In this Review, the physics of SEOP is discussed and the different production modalities are explained in the context of their clinical application. We also briefly compare SEOP to other hyperpolarization methods and conclude this paper with the outlook for biomedical applications of hyperpolarized¹²⁹Xe to lung imaging and beyond.

Herein, we demonstrate “direct”¹³C hyperpolarization of¹³C‐acetate via signal amplification by reversible exchange (SABRE). The standard SABRE homogeneous catalyst [Ir‐IMes; [IrCl(COD)(IMes)], (IMes=1,3‐bis(2,4,6‐trimethylphenyl), imidazole‐2‐ylidene; COD=cyclooctadiene)] was first activated in the presence of an auxiliary substrate (pyridine) in alcohol. Following addition of sodium 1‐¹³C‐acetate, parahydrogen bubbling within a microtesla magnetic field (i.e. under conditions of SABRE in shield enables alignment transfer to heteronuclei, SABRE‐SHEATH) resulted in positive enhancements of up to ≈100‐fold in the¹³C NMR signal compared to thermal equilibrium at 9.4 T. The present results are consistent with a mechanism of “direct” transfer of spin order from parahydrogen to¹³C spins of acetate weakly bound to the catalyst, under conditions of fast exchange with respect to the¹³C acetate resonance, but we find that relaxation dynamics at microtesla fields alter the optimal matching from the traditional SABRE‐SHEATH picture. Further development of this approach could lead to new ways to rapidly, cheaply, and simply hyperpolarize a broad range of substrates (e.g. metabolites with carboxyl groups) for various applications, including biomedical NMR and MRI of cellular and in vivo metabolism.

Hyperpolarization of 13 C-pyruvate via Signal Amplificaton By Reversibble Exchange (SABRE) is an important recent discovery because of both the relative simplicity of hyperpolarization and the central biological relevance of pyruvate as a biomolecular probe for in vitro or in vivo studies. Here, we analyze the [1,2- 13 C 2 ]pyruvate-SABRE spin system and its field dependence theoretically and experimentally. We provide first-principles analysis of the governing 4-spin dihydride- 13 C 2 Hamiltonian and numerical spin dynamics simulations of the 7-spin dihydride- 13 C 2 –CH 3 system. The analytical and the numerical results are compared to matching systematic experiments. With these methods we unravel the observed spin state mixing of singlet states and triplet states at microTesla fields and we also analyze the dynamics during transfer from micro-Tesla field to high field for detection to understand the resulting spectra from the [1,2- 13 C 2 ]pyruvate-SABRE system.