Parahydrogen Induced Polarization: A New Magnifying Glass for Examining Reactions with Hydrogen

Parahydrogen-included polarization (PHIP), its occurrence and mechanistic implications in homogeneous hydrogenation chemistry, and its appearance in the oxidative addition of H₂ to transition metal centers are described and analyzed. The PHIP phenomenon, which is characterized by unusual NMR absorptions and emissions in product spectra, arises when para-enriched H₂ is employed in hydrogenation of unsaturated organic substrates with a homogeneous metal catalyst or when para-enriched H₂ is added to a metal complex to form a metal dihydride. Examples of PHIP are found in ruthenium phosphine-catalyzed hydrogenations, catalysis by binuclear rhodium complexes, and in H₂ oxidative addition to Ir(I) complexes. The decay of polarization has been shown in the case of asymmetric hydrogenation catalyzed by Rh(chiraphos)⁺ to correlate well with the measured rate of reaction. For asymmetric hydrogenation of aprotic substrates using Noyori's Ru(BINAP)(OAc)₂ catalyst (1), PHIP is observed indicating a pairwise hydrogen transfer mechanism. Through the signal enhancement of PHIP, it has been possible to observe Rh hydride species never previously detected including binuclear complexes in the reaction of H₂ with RhCl(CO)(PR₃)₂ (R = Ph, Me) and in hydrogenation catalysis promoted by RhCl(PPh₃)₃. Also observed in the hydrogenation catalysis is the putative olefin dihydride catalytic intermediate.     

Effective PHIP Labeling of Bioactive Peptides Boosts the Intensity of the NMR Signal

A series of novel bioactive derivatives of the sunflower trypsin inhibitor‐1 (SFTI‐1) suitable for hyperpolarization by parahydrogen‐induced polarization (PHIP) was developed. The PHIP activity was achieved by labeling with L ‐propargylglycine, O‐propargyl‐L ‐tyrosine, or 4‐pentynoic acid. ¹H NMR signal enhancements (SE) of up to a factor of 70 were achieved in aqueous solution. We found that an isolated spatial location of the triple bond within the respective label and its accessibility for the hydrogenation catalyst are essential factors for the degree of signal enhancement.     

A New Ir‐NHC Catalyst for Signal Amplification by Reversible Exchange in D2O

NMR signal amplification by reversible exchange (SABRE) has been observed for pyridine, methyl nicotinate, N‐methylnicotinamide, and nicotinamide in D₂O with the new catalyst [Ir(Cl)(IDEG)(COD)] (IDEG=1,3‐bis(3,4,5‐tris(diethyleneglycol)benzyl)imidazole‐2‐ylidene). During the activation and hyperpolarization steps, exclusively D₂O was used, resulting in the first fully biocompatible SABRE system. Hyperpolarized ¹H substrate signals were observed at 42.5 MHz upon pressurizing the solution with parahydrogen at close to the Earth's magnetic field, at concentrations yielding barely detectable thermal signals. Moreover, 42‐, 26‐, 22‐, and 9‐fold enhancements were observed for nicotinamide, pyridine, methyl nicotinate, and N‐methylnicotinamide, respectively, in conventional 300 MHz studies. This research opens up new opportunities in a field in which SABRE has hitherto primarily been conducted in CD₃OD. This system uses simple hardware, leaves the substrate unaltered, and shows that SABRE is potentially suitable for clinical purposes.     

Anomalously Large Antiphase Signals from Hyperpolarized Orthohydrogen Using a MOF-Based SABRE Catalyst

Hyperpolarized orthohydrogen (o-H₂) is a frequent product of parahydrogen-based hyperpolarization approaches like signal amplification by reversible exchange (SABRE), where the hyperpolarized o-H₂ signal is usually absorptive. We describe a novel manifestation of this effect wherein large antiphase o-H₂ signals are observed, with ¹H enhancements up to ≈500-fold (effective polarization P_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 the o-H₂ resonance is manifested by a two-fold higher Rabi frequency, and the lifetime of the antiphase HP o-H₂ resonance is extended by several-fold.     

β‐Diketiminate‐Stabilized Magnesium(I) Dimers and Magnesium(II) Hydride Complexes: Synthesis,Characterization, Adduct Formation,and Reactivity Studies

The preparation and characterization of a series of magnesium(II) iodide complexes incorporating β‐diketiminate ligands of varying steric bulk and denticity, namely, [(ArNCMe)₂CH]^? (Ar=phenyl, (^PhNacnac), mesityl (^MesNacnac), or 2,6‐diisopropylphenyl (Dipp, ^DippNacnac)), [(DippNCtBu)₂CH]^? (^tBuNacnac), and [(DippNCMe)(Me₂NCH₂CH₂NCMe)CH]^? (^DmedaNacnac) are reported. The complexes [(^PhNacnac)MgI(OEt₂)], [(^MesNacnac)MgI(OEt₂)], [(^DmedaNacnac)MgI(OEt₂)], [(^MesNacnac)MgI(thf)], [(^DippNacnac)MgI(thf)], [(^tBuNacnac)MgI], and [(^tBuNacnac)MgI(DMAP)] (DMAP=4‐dimethylaminopyridine) were shown to be monomeric by X‐ray crystallography. In addition, the related β‐diketiminato beryllium and calcium iodide complexes, [(^MesNacnac)BeI] and [{(^DippNacnac)CaI(OEt₂)}₂] were prepared and crystallographically characterized. The reductions of all metal(II) iodide complexes by using various reagents were attempted. In two cases these reactions led to the magnesium(I) dimers, [(^MesNacnac)MgMg(^MesNacnac)] and [(^tBuNacnac)MgMg(^tBuNacnac)]. The reduction of a 1:1 mixture of [(^DippNacnac)MgI(OEt₂)] and [(^MesNacnac)MgI(OEt₂)] with potassium gave a low yield of the crystallographically characterized complex [(^DippNacnac)Mg(μ‐H)(μ‐I)Mg(^MesNacnac)]. All attempts to form beryllium(I) or calcium(I) dimers by reductions of [(^MesNacnac)BeI], [{(^DippNacnac)CaI(OEt₂)}₂], or [{(^tBuNacnac)CaI(thf)}₂] have so far been unsuccessful. The further reactivity of the magnesium(I) complexes [(^MesNacnac)MgMg(^MesNacnac)] and [(^tBuNacnac)MgMg(^tBuNacnac)] towards a variety of Lewis bases and unsaturated organic substrates was explored. These studies led to the complexes [(^MesNacnac)Mg(L)Mg(L)(^MesNacnac)] (L=THF or DMAP), [(^MesNacnac)Mg(μ‐AdN₆Ad)Mg(^MesNacnac)] (Ad=1‐adamantyl), [(^tBuNacnac)Mg(μ‐AdN₆Ad)Mg(^tBuNacnac)], and [(^MesNacnac)Mg(μ‐tBu₂N₂C₂O₂)Mg(^MesNacnac)] and revealed that, in general, the reactivity of the magnesium(I) dimers is inversely proportional to their steric bulk. The preparation and characterization of [(^tBuNacnac)Mg(μ‐H)₂Mg(^tBuNacnac)] has shown the compound to have different structural and physical properties to [(^tBuNacnac)MgMg(^tBuNacnac)]. Treatment of the former with DMAP has given [(^tBuNacnac)Mg(H)(DMAP)], the X‐ray crystal structure of which disclosed it to be the first structurally authenticated terminal magnesium hydride complex. Although attempts to prepare [(^MesNacnac)Mg(μ‐H)₂Mg(^MesNacnac)] were not successful, a neutron diffraction study of the corresponding magnesium(I) complex, [(^MesNacnac)MgMg(^MesNacnac)] confirmed that the compound is devoid of hydride ligands.     

The Nature of the UC Double Bond: Pushing the Stability of High‐Oxidation‐State Uranium Carbenes to the Limit

Treatment of [K(BIPM^MesH)] (BIPM^Mes={C(PPh₂NMes)₂}^2?; Mes=C₆H₂‐2,4,6‐Me₃) with [UCl₄(thf)₃] (1 equiv) afforded [U(BIPM^MesH)(Cl)₃(thf)] ( 1 ), which generated [U(BIPM^Mes)(Cl)₂(thf)₂] ( 2 ), following treatment with benzyl potassium. Attempts to oxidise 2 resulted in intractable mixtures, ligand scrambling to give [U(BIPM^Mes)₂] or the formation of [U(BIPM^MesH)(O)₂(Cl)(thf)] ( 3 ). The complex [U(BIPM^Dipp)(μ‐Cl)₄(Li)₂(OEt₂)(tmeda)] ( 4 ) (BIPM^Dipp={C(PPh₂NDipp)₂}^2?; Dipp=C₆H₃‐2,6‐iPr₂; tmeda=N,N,N′,N′‐tetramethylethylenediamine) was prepared from [Li₂(BIPM^Dipp)(tmeda)] and [UCl₄(thf)₃] and, following reflux in toluene, could be isolated as [U(BIPM^Dipp)(Cl)₂(thf)₂] ( 5 ). Treatment of 4 with iodine (0.5 equiv) afforded [U(BIPM^Dipp)(Cl)₂(μ‐Cl)₂(Li)(thf)₂] ( 6 ). Complex 6 resists oxidation, and treating 4 or 5 with N‐oxides gives [{U(BIPM^DippH)(O)₂‐ (μ‐Cl)₂Li(tmeda)] ( 7 ) and [{U(BIPM^DippH)(O)₂(μ‐Cl)}₂] ( 8 ). Treatment of 4 with tBuOLi (3 equiv) and I₂ (1 equiv) gives [U(BIPM^Dipp)(OtBu)₃(I)] ( 9 ), which represents an exceptionally rare example of a crystallographically authenticated uranium(VI)–carbon σ bond. Although 9 appears sterically saturated, it decomposes over time to give [U(BIPM^Dipp)(OtBu)₃]. Complex 4 reacts with PhCOtBu and Ph₂CO to form [U(BIPM^Dipp)(μ‐Cl)₄(Li)₂(tmeda)(OCPhtBu)] ( 10 ) and [U(BIPM^Dipp)(Cl)(μ‐Cl)₂(Li)(tmeda)(OCPh₂)] ( 11 ). In contrast, complex 5 does not react with PhCOtBu and Ph₂CO, which we attribute to steric blocking. However, complexes 5 and 6 react with PhCHO to afford (DippNPPh₂)₂C?C(H)Ph ( 12 ). Complex 9 does not react with PhCOtBu, Ph₂CO or PhCHO; this is attributed to steric blocking. Theoretical calculations have enabled a qualitative bracketing of the extent of covalency in early‐metal carbenes as a function of metal, oxidation state and the number of phosphanyl substituents, revealing modest covalent contributions to U?C double bonds.     

Catalytic Hydrogenation of Trivinyl Orthoacetate: Mechanisms Elucidated by Parahydrogen Induced Polarization

Parahydrogen (pH₂) induced polarization (PHIP) is a unique method that is used in analytical chemistry to elucidate catalytic hydrogenation pathways and to increase the signal of small metabolites in MRI and NMR. PHIP is based on adding or exchanging at least one pH₂ molecule with a target molecule. Thus, the spin order available for hyperpolarization is often limited to that of one pH₂ molecule. To break this limit, we investigated the addition of multiple pH₂ molecules to one precursor. We studied the feasibility of the simultaneous hydrogenation of three arms of trivinyl orthoacetate (TVOA) intending to obtain hyperpolarized acetate. It was found that semihydrogenated TVOA underwent a fast decomposition accompanied by several minor reactions including an exchange of geminal methylene protons of a vinyl ester with pH₂. The study shows that multiple vinyl ester groups are not suitable for a fast and clean (without any side products) hydrogenation and hyperpolarization that is desired in biochemical applications.     

A Versatile Compact Parahydrogen Membrane Reactor

We introduce a Spin Transfer Automated Reactor (STAR) that produces continuous parahydrogen induced polarization (PHIP), which is stable for hours to days. We use the PHIP variant called signal amplification by reversible exchange (SABRE), which is particularly well suited to produce continuous hyperpolarization. The STAR is operated in conjunction with benchtop (1.1 T) and high field (9.4 T) NMR magnets, highlighting the versatility of this system to operate with any NMR or MRI system. The STAR uses semipermeable membranes to efficiently deliver parahydrogen into solutions at nano to milli Tesla fields, which enables ¹H, ¹³C, and ¹⁵N hyperpolarization on a large range of substrates including drugs and metabolites. The unique features of the STAR are leveraged for important applications, including continuous hyperpolarization of metabolites, desirable for examining steady-state metabolism in vivo, as well as for continuous RASER signals suitable for the investigation of new physics.     

Seven-Membered Cyclic Potassium Diamidoalumanyls

The seven-membered cyclic potassium alumanyl species, [{SiN^Mes}AlK]₂ [{SiN^Mes}={CH₂SiMe₂N(Mes)}₂; Mes=2,4,6-Me₃C₆H₂], which adopts a dimeric structure supported by flanking K-aryl interactions, has been isolated either by direct reduction of the iodide precursor, [{SiN^Mes}AlI], or in a stepwise manner via the intermediate dialumane, [{SiN^Mes}Al]₂. Although the intermediate dialumane has not been observed by reduction of a Dipp-substituted analogue (Dipp=2,6-i-Pr₂C₆H₃), partial oxidation of the potassium alumanyl species, [{SiN^Dipp}AlK]₂, where {SiN^Dipp}={CH₂SiMe₂N(Dipp)}₂, provided the extremely encumbered dialumane [{SiN^Dipp}Al]₂. [{SiN^Dipp}AlK]₂ reacts with toluene by reductive activation of a methyl C(sp³)-H bond to provide the benzyl hydridoaluminate, [{SiN^Dipp}AlH(CH₂Ph)]K, and as a nucleophile with BPh₃ and RN=C=NR (R=i-Pr, Cy) to yield the respective Al-B- and Al-C-bonded potassium aluminaborate and alumina-amidinate products. The dimeric structure of [{SiN^Dipp}AlK]₂ can be disrupted by partial or complete sequestration of potassium. Equimolar reactions with 18-crown-6 result in the corresponding monomeric potassium alumanyl, [{SiN^Dipp}Al−K(18-cr-6)], which provides a rare example of a direct Al−K contact. In contrast, complete encapsulation of the potassium cation of [{SiN^Dipp}AlK]₂, either by an excess of 18-cr-6 or 2,2,2-cryptand, allows the respective isolation of bright orange charge-separated species comprising the ‘free’ [{SiN^Dipp}Al]⁻ alumanyl anion. Density functional theory (DFT) calculations performed on this moiety indicate HOMO-LUMO energy gaps in the of order 200–250 kJ mol⁻¹.     

Hyperpolarising Pyruvate through Signal Amplification by Reversible Exchange (SABRE)

Hyperpolarisation methods that premagnetise agents such as pyruvate are currently receiving significant attention because they produce sensitivity gains that allow disease tracking and interrogation of cellular metabolism by magnetic resonance. Here, we communicate how signal amplification by reversible exchange (SABRE) can provide strong ¹³C pyruvate signal enhancements in seconds through the formation of the novel polarisation transfer catalyst [Ir(H)₂(η²‐pyruvate)(DMSO)(IMes)]. By harnessing SABRE, strong signals for [1‐¹³C]‐ and [2‐¹³C]pyruvate in addition to a long‐lived singlet state in the [1,2‐¹³C₂] form are readily created; the latter can be observed five minutes after the initial hyperpolarisation step. We also demonstrate how this development may help with future studies of chemical reactivity.     

Transfer of parahydrogen-induced hyperpolarization to 19F

Homogeneous hydrogenations of unsaturated substrates with parahydrogen yield strong NMR signal enhancements of the transferred 1H nuclei if the symmetry of H2 is broken in the resulting hydrogenated products. This chemically induced hyperpolarization known as Parahydrogen-induced polarization (PHIP) is also transferred to other protons and heteronuclei (2H, 13C, 29Si, 31P) when the hydrogenation is initiated at low magnetic fields. Hydrogenating various fluorinated styrenes and phenylacetylenes, we show that PHIP-derived hyperpolarization is transferred to 19F not only in the Earth's magnetic field (ALTADENA condition) but also in a strong magnetic field, e.g., when carrying out the reaction in the NMR spectrometer (PASADENA condition). Upon conducting a systematic analysis of the observed PHIP transfer to 1H, 13C, and 19F in the hydrogenation products to elucidate the mechanisms that govern this parahydrogen-aided resonance transfer (PART), we conclude that high- and low-field PHIP transfer mechanisms differ in detail depending on either through-bond or through-space interactions. Substrates with high hydrogenation rates and long spin-lattice relaxation times (T1) yield the highest degree of heteronuclear hyperpolarization. Possible medical applications for hyperpolarized 19F-containing molecules as "active" contrast agents for magnetic resonance imaging (MRI) are outlined.     

“Direct” 13C Hyperpolarization of 13C‐Acetate by MicroTesla NMR Signal Amplification by Reversible Exchange (SABRE)

Herein, we demonstrate “direct” ¹³C hyperpolarization of ¹³C‐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 the ¹³C 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 to ¹³C spins of acetate weakly bound to the catalyst, under conditions of fast exchange with respect to the ¹³C 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.     

Nuclear Spin Hyperpolarization of NH2- and CH3-Substituted Pyridine and Pyrimidine Moieties by SABRE

Hyperpolarization of N-heterocycles with signal amplification by reversible exchange (SABRE) induces NMR sensitivity gains for biological molecules. Substitutions with functional groups, in particular in the ortho-position of the heterocycle, however, result in low polarization using a typical Ir catalyst with a bis-mesityl N-heterocyclic carbene ligand for SABRE, presumably due to steric hindrance. With the addition of allylamine or acetonitrile as coligands to the precatalyst chloro(1,5-cyclooctadiene)[4,5-dimethyl-1,3-bis(2,4,6-trimethylphenyl)imidazol-2-ylidene] iridium, the ¹H signal enhancement increased in several substrates with ortho NH₂ substitutions. For example, for a proton in 2,4-diaminopyrimidine, the enhancement factors increased from −7±1 to −210±20 with allylamine or to −160±10 with acetonitrile. CH₃ substituted molecules yielded maximum signal enhancements of −25±7 with acetonitrile addition, which is considerably less than the corresponding NH₂ substituted molecules, despite exhibiting similar steric size. With the more electron-donating NH₂ substitution resulting in greater enhancement, it is concluded that steric hindrance is not the only dominant factor in determining the polarizability of the CH₃ substituted compounds. The addition of allylamine increased the signal enhancement for the 290 Da trimethoprim, a molecule with a 2,4-diaminopyrimidine moiety serving as an antibacterial agent, to −70.     

Reversible Hyperpolarization of Ketoisocaproate Using Sulfoxide-containing Polarization Transfer Catalysts

The substrate scope of sulfoxide-containing magnetisation transfer catalysts is extended to hyperpolarize α-ketoisocaproate and α-ketoisocaproate-1-[¹³C]. This is achieved by forming [Ir(H)₂(κ²-ketoisocaproate)(N-heterocyclic carbene)(sulfoxide)] which transfers latent magnetism from p-H₂ via the signal amplification by reversible exchange (SABRE) process. The effect of polarization transfer field on the formation of enhanced ¹³C magnetization is evaluated. Consequently, performing SABRE in a 0.5 μT field enabled most efficient magnetisation transfer. ¹³C NMR signals for α-ketoisocaproate-1-[¹³C] in methanol-d₄ are up to 985-fold more intense than their traditional Boltzmann derived signal intensity (0.8 % ¹³C polarisation). Single crystal X-ray diffraction reveals the formation of the novel catalyst decomposition products [Ir(μ-H)(H)₂(IMes)(SO(Ph)(Me)₂)]₂ and [(Ir(H)₂(IMes)(SO(Me)₂))₂(μ-S)] when the sulfoxides methylphenylsulfoxide and dimethylsulfoxide are used respectively.     

Computational (DFT) and Experimental (EXAFS) Study of the Interaction of [Ir(IMes)(H)2(L)3] with Substrates and Co‐substrates Relevant for SABRE in Dilute Systems

Signal amplification by reversible exchange (SABRE) is an emerging hyperpolarization method in NMR spectroscopy, in which hyperpolarization is transferred through the scalar coupling network of para‐hydrogen derived hydrides in a metal complex to a reversibly bound substrate. Substrates can even be hyperpolarized at concentrations below that of the metal complex by addition of a suitable co‐substrate. Here we investigate the catalytic system used for trace detection in NMR spectroscopy with [Ir(IMes)(H)₂(L)₃]⁺ (IMes=1,3‐dimesitylimidazol‐2‐ylidene) as catalyst, pyridine as a substrate and 1‐methyl‐1,2,3‐triazole as co‐substrate in great detail. With density functional theory (DFT), validated by extended X‐ray absorption fine structure (EXAFS) experiments, we provide explanations for the relative abundance of the observed metal complexes, as well as their contribution to SABRE. We have established that the interaction between iridium and ligands cis to IMes is weaker than that with the trans ligand, and that in mixed complexes with pyridine and triazole, the latter preferentially takes up the trans position.     

Level Anti‐Crossings are a Key Factor for Understanding para‐Hydrogen‐Induced Hyperpolarization in SABRE Experiments

Various hyperpolarization methods are able to enhance the sensitivity of nuclear magnetic resonance (NMR) spectroscopy and magnetic resonance imaging (MRI) by several orders of magnitude. Among these methods are para‐hydrogen‐induced polarization (PHIP) and signal amplification by reversible exchange (SABRE), which exploit the strong nuclear alignment of para‐hydrogen. Several SABRE experiments have been reported but, so far, it has not been possible to account for the experimentally observed sign and magnetic‐field dependence of substrate polarization. Herein, we present an analysis based on level anti‐crossings (LACs), which provides a complete understanding of the SABRE effect. The field‐dependence of both net and anti‐phase polarization is measured for several ligands, which can be reproduced by the theory. The similar SABRE field‐dependence for different ligands is also explained. In general, the LAC concept allows complex spin dynamics to be unraveled, and is crucial for optimizing the performance of novel hyperpolarization methods in NMR and MRI techniques.     

Parahydrogen-Induced Polarization in Hydrogenation Reactions Mediated by a Metal-Free Catalyst

We report nuclear spin hyperpolarization of various alkenes achieved in alkyne hydrogenations with parahydrogen over a metal-free hydroborane catalyst (HCAT). Being an intramolecular frustrated Lewis pair aminoborane, HCAT utilizes a non-pairwise mechanism of H₂ transfer to alkynes that normally prevents parahydrogen-induced polarization (PHIP) from being observed. Nevertheless, the specific spin dynamics in catalytic intermediates leads to the hyperpolarization of predominantly one hydrogen in alkene. PHIP enabled the detection of important HCAT-alkyne-H₂ intermediates through substantial ¹H, ¹¹B and ¹⁵N signal enhancement and allowed advanced characterization of the catalytic process.     

Hyperpolarization of cis-15N2-Azobenzene by Parahydrogen at Ultralow Magnetic Fields**

The development of nuclear spins hyperpolarization, and the search for molecules that can be efficiently hyperpolarized is an active area in nuclear magnetic resonance. In this work we present a detailed study of SABRE SHEATH (signal amplification by reversible exchange in shield enabled alignment transfer to heteronuclei) experiments on ¹⁵N₂-azobenzene. In SABRE SHEATH experiments the nuclear spins of the target are hyperpolarized through transfer of spin polarization from parahydrogen at ultralow fields during a reversible chemical process. Azobenzene exists in two isomers, trans and cis. We show that all nuclear spins in cis-azobenzene can be efficiently hyperpolarized by SABRE at suitable magnetic fields. Enhancement factors (relative to 9.4 T) reach up to 3000 for ¹⁵N spins and up to 30 for the ¹H spins. We compare two approaches to observe either hyperpolarized magnetization of ¹⁵N/¹H spins, or hyperpolarized singlet order of the ¹⁵N spin pair. The results presented here will be useful for further experiments in which hyperpolarized cis-¹⁵N₂-azobenzene is switched by light to trans-¹⁵N₂-azobenzene for storing the produced hyperpolarization in the long-lived spin state of the ¹⁵N pair of trans-¹⁵N₂-azobenzene.     

Hyperpolarization of Pyridyl Fentalogues by Signal Amplification By Reversible Exchange (SABRE)

Fentanyl, also known as ‘jackpot’, is a synthetic opiate that is 50–100 times more potent than morphine. Clandestine laboratories produce analogues of fentanyl, known as fentalogues to circumvent legislation regarding its production. Three pyridyl fentalogues were synthesized and then hyperpolarized by signal amplification by reversible exchange (SABRE) to appraise the forensic potential of the technique. A maximum enhancement of -168-fold at 1.4 T was recorded for the ortho pyridyl ¹H nuclei. Studies of the activation parameters for the three fentalogues revealed that the ratio of ligand loss trans to hydride and hydride loss in the complex [Ir(IMes)(L)₃(H)₂]⁺ (IMes=1,3-bis(2,4,6-trimethylphenyl)imidazole-2-ylidene) ranged from 0.52 to 1.83. The fentalogue possessing the ratio closest to unity produced the largest enhancement subsequent to performing SABRE at earth's magnetic field. It was possible to hyperpolarize a pyridyl fentalogue selectively from a matrix that consisted largely of heroin (97 : 3 heroin:fentalogue) to validate the use of SABRE as a forensic tool.     

Para-hydrogen-induced polarization in rhodium complex-catalyzed hydrogenation reactions

The homogeneous hydrogenation of PhCCH catalyzed by RhClL₃, Rh(COD)L₂⁺, and Rh(COD)dppe⁺ (L  PPh₃; COD1,5-cyclooctadiene; dppe = 1,2-bis(diphenylphosphino)ethane) has been investigated using para-hydrogen-induced polarization (PHIP) which allows that in accord with earlier studies, for RHClL₃ the addition of H₂ is reversible, whereas for Rh(CO)(dppe)⁺ and Rh(COD)L₂⁺, H₂ addition in hydrogenation catalysis is irreversible.