Analysis of chemical exchange in iridium N-heterocyclic carbene complexes using heteronuclear parahydrogen-enhanced NMR.

The signal amplification by reversible exchange process (SABRE) enhances NMR signals by unlocking hidden polarization in parahydrogen through interactions with to-be-hyperpolarized substrate molecules when both are transiently bound to an Ir-based organometallic catalyst. Recent efforts focus on optimizing polarization transfer from parahydrogen-derived hydride ligands to the substrate in SABRE. However, this requires quantitative information on ligand exchange rates, which common NMR techniques struggle to provide.

Rapid lung ventilation MRI using parahydrogen-induced polarization of propane gas.

Proton-hyperpolarized contrast agents are attractive because they can be imaged on virtually any clinical MRI scanner, which is typically equipped to scan only protons rather than heteronuclei (, anything besides protons, , C, N, Xe, Na, .). Even though the lifetime of the proton spin hyperpolarization is only a few seconds, it is sufficient for inhalation and scanning of proton-hyperpolarized gas media.

Developing Hyperpolarized Butane Gas for Ventilation Lung Imaging.

NMR hyperpolarization dramatically improves the detection sensitivity of magnetic resonance through the increase in nuclear spin polarization. Because of the sensitivity increase by several orders of magnitude, additional applications have been unlocked, including imaging of gases in physiologically relevant conditions. Hyperpolarized Xe gas recently received FDA approval as the first inhalable gaseous MRI contrast agent for clinical functional lung imaging of a wide range of pulmonary diseases.

Through-bond and through-space radiofrequency amplification by stimulated emission of radiation.

Radio Amplification by Stimulated Emission of Radiation (RASER) is a phenomenon observed during nuclear magnetic resonance (NMR) experiments with strongly negatively polarized systems. This phenomenon may be utilized for the production of very narrow NMR lines, background-free NMR spectroscopy, and excitation-free sensing of chemical transformations. Recently, novel methods of producing RASER by ParaHydrogen-Induced Polarization (PHIP) were introduced.

Contrasting Metallic (Rh) and Carbidic (2D-MoC MXene) Surfaces in Olefin Hydrogenation Provides Insights on the Origin of the Pairwise Hydrogen Addition.

Kinetic studies are vital for gathering mechanistic insights into heterogeneously catalyzed hydrogenation of unsaturated organic compounds (olefins), where the Horiuti-Polanyi mechanism is ubiquitous on metal catalysts. While this mechanism envisions nonpairwise H addition due to the rapid scrambling of surface hydride (H*) species, a pairwise H addition is experimentally encountered, rationalized here based on density functional theory (DFT) simulations for the ethene (CH) hydrogenation catalyzed by two-dimensional (2D) MXene MoC(0001) surface and compared to Rh(111) surface. Results show that ethyl (CH*) hydrogenation is the rate-determining step (RDS) on MoC(0001), yet CH* formation is the RDS on Rh(111), which features a higher reaction rate and contribution from pairwise H addition compared to 2D-MoC(0001).

Modeling Ligand Exchange Kinetics in Iridium Complexes Catalyzing SABRE Nuclear Spin Hyperpolarization.

Large signal enhancements can be obtained for NMR analytes using the process of nuclear spin hyperpolarization. Organometallic complexes that bind parahydrogen can themselves become hyperpolarized. Moreover, if parahydrogen and a to-be-hyperpolarized analyte undergo chemical exchange with the organometallic complex it is possible to catalytically sensitize the detection of the analyte via hyperpolarization transfer through spin-spin coupling in this organometallic complex.

Branching-Chain Propagation of Parahydrogen-Derived Nuclear Spin Order on a Catalyst Surface.

This study reveals that, when two hydrogen atoms are produced on the surface of a catalyst (e. g., a metal nanoparticle) upon dissociation of a parahydrogen molecule, their initial nuclear spin correlation can propagate in a branching-chain fashion as they diffuse and combine with random H atoms to produce H molecules, which subsequently dissociate.

Implications for the Hydrogenation of Propyne and Propene with Parahydrogen due to the in situ Transformation of RhC to Rh/C.

NMR spectroscopy studies using parahydrogen-induced polarization have previously established the existence of the pairwise hydrogen addition route in the hydrogenation of unsaturated hydrocarbons over heterogeneous catalysts, including those based on rhodium (Rh). This pathway requires the incorporation of both hydrogen atoms from one hydrogen molecule to the same product molecule. However, the underlying mechanism for such pairwise hydrogen addition must be better understood.

N Hyperpolarization of Metronidazole Antibiotic in Aqueous Media Using Phase-Separated Signal Amplification by Reversible Exchange with Parahydrogen.

Metronidazole is a prospective hyperpolarized MRI contrast agent with potential hypoxia sensing utility for applications in cancer, stroke, neurodegenerative diseases, etc. We demonstrate a pilot procedure for production of ∼30 mM hyperpolarized [N]metronidazole in aqueous media by using a phase-separated SABRE-SHEATH hyperpolarization method, with nitrogen-15 polarization exceeding 2.2% on all three N sites achieved in less than 2 min.

Parahydrogen-Induced Polarization of N Nuclei.

Hyperpolarization techniques provide a dramatic increase in sensitivity of nuclear magnetic resonance spectroscopy and imaging. In spite of the outstanding progress in solution-state hyperpolarization of spin-1/2 nuclei, hyperpolarization of quadrupolar nuclei remains challenging. Here, hyperpolarization of quadrupolar N nuclei with natural isotopic abundance of >99 % is demonstrated.

Hyperpolarized long-lived spin state of methylene protons of 2-bromoethanol obtained from ethylene with non-equilibrium nuclear spin order.

In this work we achieve a significant overpopulation (P≈1%) of the long-lived spin state (LLS) of methylene protons in 2-bromoethan(H)ol (BrEtOD) obtained in a reaction between ethylene with non-equilibrium nuclear spin order and bromine water. Given all protons in ethylene are magnetically equivalent, its nuclear states are classified into nuclear spin isomers (NSIM) with total spin I = 2,1,0. Addition of parahydrogen to acetylene produces ethylene with a population of only those NSIMs with I = 1,0.

Toward Lung Ventilation Imaging Using Hyperpolarized Diethyl Ether Gas Contrast Agent.

Hyperpolarized Xe gas was FDA-approved as an inhalable contrast agent for magnetic resonance imaging of a wide range of pulmonary diseases in December 2022. Despite the remarkable success in clinical research settings, the widespread clinical translation of HP Xe gas faces two critical challenges: the high cost of the relatively low-throughput hyperpolarization equipment and the lack of Xe imaging capability on clinical MRI scanners, which have narrow-bandwidth electronics designed only for proton (H) imaging. To solve this translational grand challenge of gaseous hyperpolarized MRI contrast agents, here we demonstrate the utility of batch-mode production of proton-hyperpolarized diethyl ether gas via heterogeneous pairwise addition of parahydrogen to ethyl vinyl ether.

Manipulating stereoselectivity of parahydrogen addition to acetylene to unravel interconversion of ethylene nuclear spin isomers.

Symmetric molecules exist as distinct nuclear spin isomers (NSIMs). A deeper understanding of their properties, including interconversion of different NSIMs, requires efficient techniques for NSIM enrichment. In this work, selective hydrogenation of acetylene with parahydrogen (p-H) was used to achieve the enrichment of ethylene NSIMs and to study their equilibration processes.

MATRESHCA: Microtesla Apparatus for Transfer of Resonance Enhancement of Spin Hyperpolarization via Chemical Exchange and Addition.

We present an integrated, open-source device for parahydrogen-based hyperpolarization processes in the microtesla field regime with a cost of components of less than $7000. The device is designed to produce a batch of C and N hyperpolarized (HP) compounds via hydrogenative or non-hydrogenative parahydrogen-induced polarization methods that employ microtesla magnetic fields for efficient polarization transfer of parahydrogen-derived spin order to X-nuclei (e.g.

Carbon-13 Radiofrequency Amplification by Stimulated Emission of Radiation of the Hyperpolarized Ketone and Hemiketal Forms of Allyl [1-C]Pyruvate.

C hyperpolarized pyruvate is an emerging MRI contrast agent for sensing molecular events in cancer and other diseases with aberrant metabolic pathways. This metabolic contrast agent can be produced via several hyperpolarization techniques. Despite remarkable success in research settings, widespread clinical adoption faces substantial roadblocks because the current sensing technology utilized to sense this contrast agent requires the excitation of C nuclear spins that also need to be synchronized with MRI field gradient pulses.

XPS and HR TEM Elucidation of the Diversity of Titania-Supported Single-Site Ir Catalyst Performance in Spin-Selective Propene Hydrogenation.

Immobilized [Ir(COD)Cl]-Linker/TiO catalysts with linkers containing Py, P(Ph) and N(CH) functional groups were prepared. The catalysts were tested via propene hydrogenation with parahydrogen in a temperature range from 40 °C to 120 °C which was monitored via NMR. The catalytic behavior of [Ir(COD)Cl]-Linker/TiO is explained on the basis of quantitative and qualitative XPS data analysis performed for the catalysts before and after the reaction at 120 °C.

Ultra-Low-Cost Disposable Hand-Held Clinical-Scale Propane Gas Hyperpolarizer for Pulmonary Magnetic Resonance Imaging Sensing.

Hyperpolarized magnetic resonance imaging (MRI) contrast agents are revolutionizing the field of biomedical imaging. Hyperpolarized Xe-129 was recently FDA approved as an inhalable MRI contrast agent for functional lung imaging sensing. Despite success in research settings, modern Xe-129 hyperpolarizers are expensive (up to $1M), large, and complex to site and operate.

Combined homogeneous and heterogeneous hydrogenation to yield catalyst-free solutions of parahydrogen-hyperpolarized [1-C]succinate.

We show that catalyst-free aqueous solutions of hyperpolarized [1-C]succinate can be produced using parahydrogen-induced polarization (PHIP) and a combination of homogeneous and heterogeneous catalytic hydrogenation reactions. We generate hyperpolarized [1-C]fumarate PHIP using para-enriched hydrogen gas with a homogeneous ruthenium catalyst, and subsequently remove the toxic catalyst and reaction side products a purification procedure. Following this, we perform a second hydrogenation reaction using normal hydrogen gas to convert the fumarate into succinate using a solid Pd/AlO catalyst.

Hyperpolarizing DNA Nucleobases via NMR Signal Amplification by Reversible Exchange.

The present work investigates the potential for enhancing the NMR signals of DNA nucleobases by parahydrogen-based hyperpolarization. Signal amplification by reversible exchange (SABRE) and SABRE in Shield Enables Alignment Transfer to Heteronuclei (SABRE-SHEATH) of selected DNA nucleobases is demonstrated with the enhancement () of H, N, and/or C spins in 3-methyladenine, cytosine, and 6-O-guanine. Solutions of the standard SABRE homogenous catalyst Ir(1,5-cyclooctadeine)(1,3-bis(2,4,6-trimethylphenyl)imidazolium)Cl ("IrIMes") and a given nucleobase in deuterated ethanol/water solutions yielded low H values (≤10), likely reflecting weak catalyst binding.

Spin Hyperpolarization in Modern Magnetic Resonance.

Magnetic resonance techniques are successfully utilized in a broad range of scientific disciplines and in various practical applications, with medical magnetic resonance imaging being the most widely known example. Currently, both fundamental and applied magnetic resonance are enjoying a major boost owing to the rapidly developing field of spin hyperpolarization. Hyperpolarization techniques are able to enhance signal intensities in magnetic resonance by several orders of magnitude, and thus to largely overcome its major disadvantage of relatively low sensitivity.

Subsecond Three-Dimensional Nitrogen-15 Magnetic Resonance Imaging Facilitated by Parahydrogen-Based Hyperpolarization.

Magnetic resonance imaging (MRI) provides unique information about the internal structure and function of living organisms in a non-invasive way. The use of conventional proton MRI for the observation of real-time metabolism is hampered by the dominant signals of water and fat, which are abundant in living organisms. Heteronuclear MRI in conjunction with the hyperpolarization methods does not encounter this issue.

Through-Space Multinuclear Magnetic Resonance Signal Enhancement Induced by Parahydrogen and Radiofrequency Amplification by Stimulated Emission of Radiation.

Hyperpolarized (, polarized far beyond the thermal equilibrium) nuclear spins can result in the radiofrequency amplification by stimulated emission of radiation (RASER) effect. Here, we show the utility of RASER to amplify nuclear magnetic resonance (NMR) signals of solute and solvent molecules in the liquid state. Specifically, parahydrogen-induced RASER was used to spontaneously enhance nuclear spin polarization of protons and heteronuclei (here F and P) in a wide range of molecules.

Frozen water NMR lineshape analysis enables absolute polarization quantification.

Typical magnetic resonance experiments are routinely limited by weak signal responses. In some cases, the low intrinsic sensitivity can be alleviated by the implementation of hyperpolarization technologies. Dissolution-dynamic nuclear polarization offers a means of hyperpolarizing small molecules.

Mechanisms of Methylenecyclobutane Hydrogenation over Supported Metal Catalysts Studied by Parahydrogen-Induced Polarization Technique.

In this work the mechanism of methylenecyclobutane hydrogenation over titania-supported Rh, Pt and Pd catalysts was investigated using parahydrogen-induced polarization (PHIP) technique. It was found that methylenecyclobutane hydrogenation leads to formation of a mixture of reaction products including cyclic (1-methylcyclobutene, methylcyclobutane), linear (1-pentene, cis-2-pentene, trans-2-pentene, pentane) and branched (isoprene, 2-methyl-1-butene, 2-methyl-2-butene, isopentane) compounds. Generally, at lower temperatures (150-350 °C) the major reaction product was methylcyclobutane while higher temperature of 450 °C favors the formation of branched products isoprene, 2-methyl-1-butene and 2-methyl-2-butene.