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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. We also show that pulsed methods (including pulsed field nulling) coherently and selectively pump such singlets, affording a significant enhancement on the resulting hyperpolarization. [ABSTRACT FROM AUTHOR]

Diazirine moieties are chemically stable and have been incorporated into biomolecules without impediment of biological activity. The 15N2 labeled diazirines are appealing motifs for hyperpolarization supporting relaxation protected states with long‐lived lifetimes. The (‐CH15N2) diazirine groups investigated here are analogues to methyl groups, which provides the opportunity to transfer polarization stored on a relaxation protected (‐CH15N2) moiety to 1H, thus combining the advantages of long lifetimes of 15N polarization with superior sensitivity of 1H detection. Despite the proximity of 1H to 15N nuclei in the diazirine moiety, 15N T1 times of up to (4.6±0.4) min and singlet lifetimes Ts of up to (17.5±3.8) min are observed. Furthermore, we found terminal diazirines to support hyperpolarized 1H2 singlet states in CH2 groups of chiral molecules. The singlet lifetime of 1H singlets is up to (9.2±1.8) min, thus exceeding 1H T1 relaxation time (at 8.45 T) by a factor of ≈100. [ABSTRACT FROM AUTHOR]

In the majority of hydrogenative parahydrogen-induced polarization (PHIP) experiments, the hydrogen molecule undergoes pairwise cis addition to an unsaturated precursor to occupy vicinal positions on the product molecule. However, some ruthenium-based hydrogenation catalysts induce geminal hydrogenation, leading to a reaction product in which the two hydrogen atoms are transferred to the same carbon centre, forming a methylene ( CH 2 ) group. The singlet order of parahydrogen is substantially retained over the geminal hydrogenation reaction, giving rise to a singlet-hyperpolarized CH 2 group. Although the T 1 relaxation times of the methylene protons are often short, the singlet order has a long lifetime, provided that singlet-triplet mixing is suppressed, either by chemical equivalence of the protons or by applying a resonant radiofrequency field. The long lifetime of the singlet order enables the accumulation of hyperpolarization during the slow hydrogenation reaction. We introduce a kinetic model for the behaviour of the observed hyperpolarized signals, including both the chemical kinetics and the spin dynamics of the reacting molecules. Our work demonstrates the feasibility of producing singlet-hyperpolarized methylene moieties by parahydrogen-induced polarization. This potentially extends the range of molecular agents which may be generated in a hyperpolarized state by chemical reactions of parahydrogen., Competing Interests: The authors declare that they have no conflict of interest., (Copyright: © 2020 Laurynas Dagys et al.)

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 via 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. Interestingly, we also demonstrated that this transformation could be applied to dipeptides without racemization. Furthermore, 14 N 2 and 15 N 2 isotopomers can be obtained, emphasizing a key trans-imination step when using 15 NH 3 . In addition, we report the first experimental observation of 14 N/ 15 N isotopomers directly creating an asymmetric carbon. Finally, the 15 N 2 -diazirine from l-tyrosine was hyperpolarized by a parahydrogen-based method (SABRE-SHEATH), demonstrating the products' utility as hyperpolarized molecular tag.

Diazirine moieties are chemically stable and have been incorporated into biomolecules without impediment of biological activity. The 15 N 2 labeled diazirines are appealing motifs for hyperpolarization supporting relaxation protected states with long-lived lifetimes. The (-CH 15 N 2 ) diazirine groups investigated here are analogues to methyl groups, which provides the opportunity to transfer polarization stored on a relaxation protected (-CH 15 N 2 ) moiety to 1 H, thus combining the advantages of long lifetimes of 15 N polarization with superior sensitivity of 1 H detection. Despite the proximity of 1 H to 15 N nuclei in the diazirine moiety, 15 N T 1 times of up to (4.6±0.4) min and singlet lifetimes T s of up to (17.5±3.8) min are observed. Furthermore, we found terminal diazirines to support hyperpolarized 1 H 2 singlet states in CH 2 groups of chiral molecules. The singlet lifetime of 1 H singlets is up to (9.2±1.8) min, thus exceeding 1 H T 1 relaxation time (at 8.45 T) by a factor of ≈100., (© 2019 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.)

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, 15 N 2 -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. Our investigations reveal the critical role of Lewis basic additives, including water, on achieving SABRE-promoted hyperpolarization. The application of this strategy to a 15 N 2 -diazirine-containing choline derivative demonstrates the potential of 15 N 2 -diazirines as molecular imaging tags for biomedical applications., (© 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Parahydrogen is an inexpensive and readily available source of hyperpolarization used to enhance magnetic resonance signals by up to four orders of magnitude above thermal signals obtained at ∼10 T. A significant challenge for applications is fast signal decay after hyperpolarization. Here we use parahydrogen-based polarization transfer catalysis at microtesla fields (first introduced as SABRE-SHEATH) to hyperpolarize 13 C 2 spin pairs and find decay time constants of 12 s for magnetization at 0.3 mT, which are extended to 2 min at that same field, when long-lived singlet states are hyperpolarized instead. Enhancements over thermal at 8.5 T are between 30 and 170 fold (0.02 to 0.12% polarization). We control the spin dynamics of polarization transfer by choice of microtesla field, allowing for deliberate hyperpolarization of either magnetization or long-lived singlet states. Density functional theory calculations and experimental evidence identify two energetically close mechanisms for polarization transfer: First, a model that involves direct binding of the 13 C 2 pair to the polarization transfer catalyst and, second, a model transferring polarization through auxiliary protons in substrates.

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., (© 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)