Search

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 ( ε ) of 1 H, 15 N, and/or 13 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 1 H ε values (≤10), likely reflecting weak catalyst binding. However, we achieved natural-abundance enhancement of 15 N signals for 3-methyladenine of ~3300 and ~1900 for the imidazole ring nitrogen atoms. 1 H and 15 N 3-methyladenine studies revealed that methylation of adenine affords preferential binding of the imidazole ring over the pyrimidine ring. Interestingly, signal enhancements ( ε ~240) of both 15 N atoms for doubly labelled cytosine reveal the preferential binding of specific tautomer(s), thus giving insight into the matching of polarization-transfer and tautomerization time scales. 13 C enhancements of up to nearly 50-fold were also obtained for this cytosine isotopomer. These efforts may enable the future investigation of processes underlying cellular function and/or dysfunction, including how DNA nucleobase tautomerization influences mismatching in base-pairing.

Parahydrogen-induced polarization of 13 C nuclei by side-arm hydrogenation (PHIP-SAH) for [1- 13 C]acetate and [1- 13 C]pyruvate esters with application of PH-INEPT-type pulse sequences for 1 H to 13 C polarization transfer is reported, and its efficiency is compared with that of polarization transfer based on magnetic field cycling (MFC). The pulse-sequence transfer approach may have its merits in some applications because the entire hyperpolarization procedure is implemented directly in an NMR or MRI instrument, whereas MFC requires a controlled field variation at low magnetic fields. Optimization of the PH-INEPT-type transfer sequences resulted in 13 C polarization values of 0.66 ± 0.04% and 0.19 ± 0.02% for allyl [1- 13 C]pyruvate and ethyl [1- 13 C]acetate, respectively, which is lower than the corresponding polarization levels obtained with MFC for 1 H to 13 C polarization transfer (3.95 ± 0.05% and 0.65 ± 0.05% for allyl [1- 13 C]pyruvate and ethyl [1- 13 C]acetate, respectively). Nevertheless, a significant 13 C NMR signal enhancement with respect to thermal polarization allowed us to perform 13 C MR imaging of both biologically relevant hyperpolarized molecules which can be used to produce useful contrast agents for the in vivo imaging applications.

Supporting two metal binding sites by a tailored polydentate trop-based (trop = 5 H -dibenzo[ a , d ]cyclohepten-5-yl) ligand yields highly unsymmetric homobimetallic rhodium(i) complexes. Their reaction with hydrogen rapidly forms Rh hydrides that undergo an intramolecular semihydrogenation of two C[triple bond, length as m-dash]C bonds of the trop ligand. This reaction is chemoselective and converts C[triple bond, length as m-dash]C bonds to a bridging carbene and an olefinic ligand in the first and the second semihydrogenation steps, respectively. Stabilization by a bridging diphosphine ligand allows characterization of a Rh hydride species by advanced NMR techniques and may provide insight into possible elementary steps of H 2 activation by interfacial sites of heterogeneous Rh/C catalysts., (This journal is © The Royal Society of Chemistry 2019.)

Signal Amplification By Reversible Exchange (SABRE) is a new and rapidly developing hyperpolarization technique. The recent discovery of Spin-Lock Induced Crossing SABRE (SLIC-SABRE) showed that high field hyperpolarization transfer techniques developed so far were optimized for singlet spin order that does not coincide with the experimentally produced spin state. Here, we investigated the SLIC-SABRE approach and the most advanced quantitative theoretical SABRE model to date. Our goal is to achieve the highest possible polarization with SLIC-SABRE at high field using the standard SABRE system, IrIMes catalyst with pyridine. We demonstrated the accuracy of the SABRE model describing the effects of various physical parameters such as the amplitude and frequency of the radio frequency field, and the effects of chemical parameters such as the exchange rate constants. By fitting the model to the experimental data, the effective life time of the SABRE complex was estimated, as well as the entropy and enthalpy of the complex-dissociation reaction. We show, for the first time, that this SLIC-SABRE model can be useful for the evaluation of the chemical exchange parameters that are very important for the production of highly polarized contrast agents via SABRE.

Hyperpolarized forms of 1- 13 C-acetates and 1- 13 C-pyruvates are used as diagnostic contrast agents for molecular imaging of many diseases and disorders. Here, we report the synthetic preparation of 1- 13 C isotopically enriched and pure from solvent acetates and pyruvates derivatized with unsaturated ester moiety. The reported unsaturated precursors can be employed for NMR hyperpolarization of 1- 13 C-acetates and 1- 13 C-pyruvates via parahydrogen-induced polarization (PHIP). In this PHIP variant, Side arm hydrogenation (SAH) of unsaturated ester moiety is followed by the polarization transfer from nascent parahydrogen protons to 13 C nucleus via magnetic field cycling procedure to achieve hyperpolarization of 13 C nuclear spins. This work reports the synthesis of PHIP-SAH precursors: vinyl 1- 13 C-acetate (55% yield), allyl 1- 13 C-acetate (70% yield), propargyl 1- 13 C-acetate (45% yield), allyl 1- 13 C-pyruvate (60% yield), and propargyl 1- 13 C-pyruvate (35% yield). Feasibility of PHIP-SAH 13 C hyperpolarization was verified by 13 C NMR spectroscopy: hyperpolarized allyl 1- 13 C-pyruvate was produced from propargyl 1- 13 C-pyruvate with 13 C polarization of ∼3.2% in CD 3 OD and ∼0.7% in D 2 O. 13 C magnetic resonance imaging is demonstrated with hyperpolarized 1- 13 C-pyruvate in aqueous medium., Competing Interests: The authors declare no competing financial interest.

Mechanistic insight into the semihydrogenation of 1-butyne and 2-butyne on Cu nanoparticles supported on partially dehydroxylated silica (Cu/SiO 2-700 ) was obtained using parahydrogen. Hydrogenation of 1-butyne over Cu/SiO 2-700 yielded 1-butene with ≥97% selectivity. The surface modification of this catalyst with tricyclohexylphosphine (PCy 3 ) increased the selectivity to 1-butene up to nearly 100%, although at the expense of reduced catalytic activity. Similar trends were observed in the hydrogenation of 2-butyne, where Cu/SiO 2-700 provided a selectivity to 2-butene in the range of 72-100% depending on the reaction conditions, while the catalyst modified with PCy 3 again demonstrated nearly 100% selectivity. Parahydrogen-induced polarization effects observed in hydrogenation reactions catalyzed by copper-based catalysts demonstrate the viability of pairwise hydrogen addition over these catalysts. Contribution of pairwise hydrogen addition to 1-butyne was estimated to be at least 0.2-0.6% for unmodified Cu/SiO 2-700 and ≥2.7% for Cu/SiO 2-700 modified with PCy 3 , highlighting the effect of surface modification with the tricyclohexylphosphine ligand.

1 H MRI of gases can potentially enable functional lung imaging to probe gas ventilation and other functions. In this work, 1 H MR images of hyperpolarized and thermally polarized propane gas were obtained using UTE (ultrashort echo time) pulse sequence. A 2D image of thermally polarized propane gas with ~0.9×0.9 mm 2 spatial resolution was obtained in less than 2 seconds, demonstrating that even non-hyperpolarized hydrocarbon gases can be successfully utilized for conventional proton MRI. The experiments were also performed with hyperpolarized propane gas and demonstrated acquisition of high-resolution multi-slice FLASH 2D images in ca. 510 s and non slice-selective 2D UTE MRI images in ca. 2 s. The UTE approach adopted in this study can be potentially used for medical lung imaging. Furthermore, the possibility to combine UTE with selective suppression of 1 H signals from one of the two gases in a mixture is demonstrated in this MRI study. The latter can be useful for visualizing industrially important processes where several gases may be present, e.g., gas-solid catalytic reactions.

An experimental approach for the production of catalyst-free hyperpolarised ethanol solution in water via heterogeneous hydrogenation of vinyl acetate with parahydrogen and the subsequent hydrolysis of ethyl acetate was demonstrated. For an efficient hydrogenation, liquid vinyl acetate was transferred to the gas phase by parahydrogen bubbling and almost completely converted to ethyl acetate with Rh/TiO2 catalyst. Subsequent dissolution of ethyl acetate gas in water containing OH(-) ions led to the formation of catalyst- and organic solvent-free hyperpolarised ethanol and sodium acetate. These results represent the first demonstration of catalyst- and organic solvent-free hyperpolarised ethanol production achieved by heterogeneous hydrogenation of vinyl acetate vapour with parahydrogen and the subsequent ethyl acetate hydrolysis.

In the present study we analyze the factors which can lower hyperpolarization of fluids produced in a continuous flow regime by the parahydrogen-induced polarization technique. We use the findings of this analysis to examine the flow rate dependence of propane hyperpolarization produced in the heterogeneous propylene hydrogenation by parahydrogen over Rh/TiO2 catalyst. We have estimated the maximum attainable propane (1)H hyperpolarization yield and the corrected percentage of pairwise hydrogen addition in heterogeneous hydrogenation, which was found to be ∼7%. The approach developed for polarization analysis is useful for the optimization of experimental setup and reaction conditions to obtain maximum hyperpolarization for parahydrogen-based catalyst-free continuously generated fluids applicable in biomedical magnetic resonance imaging.

Activation of a catalyst [IrCl(COD)(IMes)] (IMes = 1,3-bis(2,4,6-trimethylphenyl)imidazol-2-ylidene; COD = cyclooctadiene)] for signal amplification by reversible exchange (SABRE) was monitored by in situ hyperpolarized proton NMR at 9.4 T. During the catalyst-activation process, the COD moiety undergoes hydrogenation that leads to its complete removal from the Ir complex. A transient hydride intermediate of the catalyst is observed via its hyperpolarized signatures, which could not be detected using conventional nonhyperpolarized solution NMR. SABRE enhancement of the pyridine substrate can be fully rendered only after removal of the COD moiety; failure to properly activate the catalyst in the presence of sufficient substrate can lead to irreversible deactivation consistent with oligomerization of the catalyst molecules. Following catalyst activation, results from selective RF-saturation studies support the hypothesis that substrate polarization at high field arises from nuclear cross-relaxation with hyperpolarized (1)H spins of the hydride/orthohydrogen spin bath. Importantly, the chemical changes that accompanied the catalyst's full activation were also found to endow the catalyst with water solubility, here used to demonstrate SABRE hyperpolarization of nicotinamide in water without the need for any organic cosolvent--paving the way to various biomedical applications of SABRE hyperpolarization methods.

Catalysis is vital to industrial chemistry, and the optimization of catalytic reactors attracts considerable resources. It has proven challenging to correlate the active regions in heterogeneous catalyst beds with morphology and to monitor multistep reactions within the bed. We demonstrate techniques, using magnetic resonance imaging and para-hydrogen (p-H2) polarization, that allow direct visualization of gas-phase flow and the density of active catalyst in a packed-bed microreactor, as well as control over the dynamics of the polarized state in space and time to facilitate the study of subsequent reactions. These procedures are suitable for characterizing reactors and reactions in microfluidic devices where low sensitivity of conventional magnetic resonance would otherwise be the limiting factor.