parahydrogen-induced polarization: accumulating long-lived singlet order on methylene proton pairs.

In the majority of hydrogenative parahydrogen-induced polarization (PHIP) experiments, the hydrogen molecule undergoes pairwise addition to an unsaturated precursor to occupy vicinal positions on the product molecule. However, some ruthenium-based hydrogenation catalysts induce hydrogenation, leading to a reaction product in which the two hydrogen atoms are transferred to the same carbon centre, forming a methylene () group. The singlet order of parahydrogen is substantially retained over the hydrogenation reaction, giving rise to a singlet-hyperpolarized group.

Rational ligand choice extends the SABRE substrate scope.

Here we report on chelating ligands for Signal Amplification By Reversible Exchange (SABRE) catalysts that permit hyperpolarisation on otherwise sterically hindered substrates. We demonstrate H enhancements of ∼100-fold over 8.5 T thermal for 2-substituted pyridines, and smaller, yet significant enhancements for provitamin B and caffeine.

Iodonitrene in Action: Direct Transformation of Amino Acids into Terminal Diazirines and N-Diazirines and Their Application as Hyperpolarized Markers.

A one-pot metal-free conversion of unprotected amino acids to terminal diazirines has been developed using phenyliodonium diacetate (PIDA) and ammonia. This PIDA-mediated transformation occurs three consecutive reactions and involves an iodonitrene intermediate. This method is tolerant to most functional groups found on the lateral chain of amino acids, it is operationally simple, and it can be scaled up to provide multigram quantities of diazirine.

Selective hyperpolarization of heteronuclear singlet states via pulsed microtesla SABRE.

Signal Amplification By Reversible Exchange (SABRE) and its heteronuclear variant SABRE in SHield Enables Alignment Transfer to Heteronuclei create large nuclear magnetization in target ligands, exploiting level crossings in an iridium catalyst that transiently binds both the ligands and parahydrogen. This requires a specific, small magnetic field to match Zeeman splittings to scalar couplings. Here, we explore a different strategy, direct creation of heteronuclear singlet states in the target ligands, which produces enhanced signals at other field strengths, including zero field.

Terminal Diazirines Enable Reverse Polarization Transfer from N Singlets.

Diazirine moieties are chemically stable and have been incorporated into biomolecules without impediment of biological activity. The N labeled diazirines are appealing motifs for hyperpolarization supporting relaxation protected states with long-lived lifetimes. The (-CH N ) diazirine groups investigated here are analogues to methyl groups, which provides the opportunity to transfer polarization stored on a relaxation protected (-CH N ) moiety to H, thus combining the advantages of long lifetimes of N polarization with superior sensitivity of H detection.

Unveiling coherently driven hyperpolarization dynamics in signal amplification by reversible exchange.

Signal amplification by reversible exchange (SABRE) is an efficient method to hyperpolarize spin-1/2 nuclei and affords signals that are orders of magnitude larger than those obtained by thermal spin polarization. Direct polarization transfer to heteronuclei such as C or N has been optimized at static microTesla fields or using coherence transfer at high field, and relies on steady state exchange with the polarization transfer catalyst dictated by chemical kinetics. Here we demonstrate that pulsing the excitation field induces complex coherent polarization transfer dynamics, but in fact pulsing with a roughly 1% duty cycle on resonance produces more magnetization than constantly being on resonance.

Diazirines as Potential Molecular Imaging Tags: Probing the Requirements for Efficient and Long-Lived SABRE-Induced Hyperpolarization.

Diazirines are an attractive class of potential molecular tags for magnetic resonance imaging owing to their biocompatibility and ease of incorporation into a large variety of molecules. As recently reported, N -diazirine can be hyperpolarized by the SABRE-SHEATH method, sustaining both singlet and magnetization states, thus offering a path to long-lived polarization storage. Herein, we show the generality of this approach by illustrating that the diazirine tag alone is sufficient for achieving excellent signal enhancements with long-lasting polarization.

The Absence of Quadrupolar Nuclei Facilitates Efficient C Hyperpolarization via Reversible Exchange with Parahydrogen.

Nuclear spin hyperpolarization techniques are revolutionizing the field of C molecular MRI. While dissolution dynamic nuclear polarization (d-DNP) is currently the leading technique, it is generally slow (requiring ≈1 h) and costly (≈$USD10 ). As a consequence of carbon's central place in biochemistry, tremendous progress using C d-DNP bioimaging has been demonstrated to date including a number of clinical trials.

Direct Hyperpolarization of Nitrogen-15 in Aqueous Media with Parahydrogen in Reversible Exchange.

Signal amplification by reversible exchange (SABRE) is an inexpensive, fast, and even continuous hyperpolarization technique that uses para-hydrogen as hyperpolarization source. However, current SABRE faces a number of stumbling blocks for translation to biochemical and clinical settings. Difficulties include inefficient polarization in water, relatively short-lived H-polarization, and relatively limited substrate scope.

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

Signal Amplification by Reversible Exchange (SABRE) is a fast and convenient NMR hyperpolarization method that uses cheap and readily available -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.

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

NMR with thermal polarization requires relatively concentrated samples, particularly for nuclei with low abundance and low gyromagnetic ratios, such as (15) N. We expand the substrate scope of SABRE, a recently introduced hyperpolarization method, to allow access to (15) N-enriched Schiff bases. These substrates show fractional (15) N polarization levels of up to 2 % while having only minimal (1) H enhancements.

Para-hydrogen perspectives in hyperpolarized NMR.

The first instance of para-hydrogen induced polarization (PHIP) in an NMR experiment was serendipitously observed in the 1980s while investigating a hydrogenation reaction (Seldler et al., 1983; Bowers and Weitekamp, 1986, 1987; Eisenschmid et al., 1987) [1-4].

Fundamental aspects of parahydrogen enhanced low-field nuclear magnetic resonance.

We report new phenomena in low-field 1H nuclear magnetic resonance (NMR) spectroscopy using parahydrogen induced polarization (PHIP), enabling determination of chemical shift differences, δν, and the scalar coupling constant J. NMR experiments performed with thermal polarization in millitesla magnetic fields do not allow the determination of scalar coupling constants for homonuclear coupled spins in the inverse weak coupling regime (δν View Article and Find Full Text PDF

Online monitoring of intelligent polymers for drug release with hyperpolarized xenon.

Welcome to the guest zone: By combining hyperpolarized xenon and simple low-field NMR devices it is possible to obtain more control over hydrogels that show potential as drug delivery systems. An alternative way of polymer swelling-degree determination is demonstrated with real-time NMR analysis. An ideal region for solvent uptake can be defined in which the absorbed solvent molecules are completely confined in the nano-porous network of the hydrogel.

Para-hydrogen induced polarization of amino acids, peptides and deuterium-hydrogen gas.

Signal Amplification by Reversible-Exchange (SABRE) is a method of hyperpolarizing substrates by polarization transfer from para-hydrogen without hydrogenation. Here, we demonstrate that this method can be applied to hyperpolarize small amounts of all proteinogenic amino acids and some chosen peptides down to the nanomole regime and can be detected in a single scan in low-magnetic fields down to 0.25 mT (10 kHz proton frequency).

Selective drug trace detection with low-field NMR.

Advances with para-hydrogen induced polarization open up new fields of applications for portable low-field NMR. Here we report the possibility of tracing drugs down to the micromolar regime. We could selectively polarize nicotine quantities similar to those found in one cigarette.