Chemical reaction monitoring using zero-field nuclear magnetic resonance enables study of heterogeneous samples in metal containers

We demonstrate that heterogeneous/biphasic chemical reactions can be monitored with high spectroscopic resolution using zero-field nuclear magnetic resonance spectroscopy. This is possible because magnetic susceptibility broadening is negligible at ultralow magnetic fields. We show the two-step hydrogenation of dimethyl acetylenedicarboxylate with para-enriched hydrogen gas in conventional glass NMR tubes, as well as in a titanium tube. The low frequency zero-field NMR signals ensure that there is no significant signal attenuation arising from shielding by the electrically conductive sample container. This method paves the way for in situ monitoring of reactions in complex heterogeneous multiphase systems and in reactors made of conductive materials while maintaining resolution and chemical specificity

Branching-chain propagation of parahydrogen-derived nuclear spin order on a catalyst surface

When a parahydrogen molecule dissociates on a surface of a heterogeneous catalyst (e.g., of a metal nanoparticle), the correlation of the nuclear spins initially inherited by the two surface H atoms may be shared with other surface hydrogens as they diffuse and combine with random H atoms to produce H2 molecules which subsequently dissociate. This branching-chain-type propagation of nuclear spin order leads to its gradual dilution but at the same time is accompanied by an increase in the number of H atoms that share nuclear spin order. These conclusions, confirmed by the spin density matrix calculations, may be relevant in the context of parahydrogen-induced polarization (PHIP) in heterogeneous hydrogenations catalyzed by supported metal catalysts, observation of which apparently contradicts the accepted non-pairwise mechanism of hydrogen addition to an unsaturated substrate over such catalysts. The potential consequences of the reported findings are discussed in the context of PHIP effects and beyond

Solvent effects in hyperpolarization of 15N nuclei in [15N3]metronidazole and [15N3]nimorazole antibiotics via SABRE-SHEATH

Metronidazole and nimorazole are antibiotics of a nitroimidazole group originally designed for acting on anaerobic bacteria. These antibiotics may be potentially utilized as hypoxia radiosensitizers for the treatment of cancerous tumors. Hyperpolarization of 15N nuclei in these compounds using SABRE-SHEATH (Signal Amplification By Reversible Exchange in SHield Enables Alignment Transfer to Heteronuclei) approach provides dramatic enhancement of detection sensitivity of these analytes using magnetic resonance spectroscopy and imaging. Methanol-d4 is conventionally employed as a solvent in SABRE hyperpolarization process. Herein, we investigate SABRE-SHEATH hyperpolarization of isotopically labeled [15N3]metronidazole and [15N3]nimorazole in nondeuterated methanol-h4 and ethanol-h6 solvents (with the latter one being more preferable for biomedical applications due to its significantly lower toxicity). Optimization of hyperpolarization parameters, such as polarization transfer magnetic field, temperature, parahydrogen flow rate and pressure, allowed us to obtain an average 15N polarization of up to ca. 7.6% for both substrates. The highest 15N polarizations were observed in methanol-d4 for [15N3]metronidazole and in ethanol-h6 for [15N3]nimorazole. At a clinically relevant magnetic field of 1.4 T the 15N nuclei of these substrates possess long characteristic hyperpolarization lifetimes (T1) in the range from ca. 1 to ca. 7 min, with the longest relaxation observed for 15NO2 sites. This study represents a major step toward SABRE in more biocompatible solvents, such as ethanol, and also paves the way for future utilization of these hyperpolarized nitroimidazoles as molecular contrast agents for MRI visualization of tumors

Combined Homogeneous and Heterogeneous Hydrogenation with Parahydrogen to Yield Catalyst-Free Solutions of Hyperpolarized [1-13C]Succinate

We show that catalyst-free aqueous solutions of hyperpolarized [1-13C]succinate can be produced using parahydrogen-induced polarization (PHIP) and a combination of homogeneous and heterogeneous catalytic hydrogenation reactions. We generate hyperpolarized [1-13C]fumarate at 23% 13C polarization via PHIP with a homogeneous ruthenium catalyst, and subsequently remove the toxic catalyst and reaction side products via a purification procedure. Following this, we perform a second hydrogenation reaction to convert the fumarate into succinate using a solid Pd/Al2O3 catalyst. The catalyst is filtered off to yield a clean aqueous solution containing [1-13C]succinate at 11.9% 13C polarization for the hyperpolarized molecules. In this proof-of-principle demonstration we simplified the purification procedure by adding unpolarized fumarate to the mixtures so the observed succinate polarization was lower, but this step is not necessary for applications. This inexpensive polarization protocol has a turnover time of a few minutes, and represents a major advance for in vivo applications of [1-13C]succinate as a hyperpolarized contrast agent

Pairwise hydrogen addition in the selective semihydrogenation of alkynes on silica-supported Cu catalysts

Mechanistic insight into the semihydrogenation of 1-butyne and 2-butyne on Cu nanoparticles supported on partially dehydroxylated silica (Cu/SiO2-700) was obtained using parahydrogen. Hydrogenation of 1-butyne over Cu/SiO2-700 yielded 1-butene with ≥97% selectivity. The surface modification of this catalyst with tricyclohexylphosphine (PCy3) 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/SiO2-700 provided a selectivity to 2-butene in the range of 72–100% depending on the reaction conditions, while the catalyst modified with PCy3 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/SiO2-700 and ≥2.7% for Cu/SiO2-700 modified with PCy3, highlighting the effect of surface modification with the tricyclohexylphosphine ligand.ISSN:2041-6520ISSN:2041-653

Chemical Reaction Monitoring Using Zero-Field Nuclear Magnetic Resonance Enables Study of Heterogeneous Samples in Metal Containers

We demonstrate that heterogeneous/biphasic chemical reactions can be monitored with high spectroscopic resolution using zero-field nuclear magnetic resonance. This is possible because magnetic susceptibility broadening is insignificant at ultralow magnetic fields. We show the two-step hydrogenation of dimethyl acetylenedicarboxylate with para-enriched hydrogen gas in conventional glass NMR tubes, as well as in a titanium tube. The low frequency zero-field NMR signals ensure that there is no significant signal attenuation due to shielding by the electrically conductive sample container. This method paves the way for in situ monitoring of reactions in complex heterogeneous multiphase systems and in reactors made from conductive materials without magnetic susceptibility induced line broadening.</div

Chemical Reaction Monitoring using Zero‐Field Nuclear Magnetic Resonance Enables Study of Heterogeneous Samples in Metal Containers

We demonstrate that heterogeneous/biphasic chemical reactions can be monitored with high spectroscopic resolution using zero-field nuclear magnetic resonance spectroscopy. This is possible because magnetic susceptibility broadening is negligible at ultralow magnetic fields. We show the two-step hydrogenation of dimethyl acetylenedicarboxylate with para-enriched hydrogen gas in conventional glass NMR tubes, as well as in a titanium tube. The low frequency zero-field NMR signals ensure that there is no significant signal attenuation arising from shielding by the electrically conductive sample container. This method paves the way for in situ monitoring of reactions in complex heterogeneous multiphase systems and in reactors made of conductive materials while maintaining resolution and chemical specificity

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, requires efficient techniques for NSIMs enrichment. Selective hydrogenation of acetylene with parahydrogen (p-H2) was used to achieve the enrichment of ethylene NSIMs and to study their equilibration processes. The effect of stereoselectivity of H2 addition to acetylene on the imbalance of ethylene NSIMs was experimentally demonstrated by using different heterogeneous catalysts (an immobilized Ir complex and two supported Pd catalysts). The interconversion of NSIMs with time during ethylene storage was studied with NMR spectroscopy by reacting ethylene with bromine water which renders the p-H2-derived protons in the produced 2-bromoethan(2H)ol (BrEtOD) magnetically inequivalent, thereby revealing the non-equilibrium nuclear spin order of ethylene. A thorough analysis of the shape and transformation of the 1H NMR spectra of hyperpolarized BrEtOD allowed us to reveal the initial distribution of produced ethylene NSIMs and their equilibration processes. Comparison of the results obtained with different catalysts was key to properly attributing the derived characteristic time constants to different NSIMs interconversion processes: ~ 3-6 s for interconversion between NSIMs with the same inversion symmetry (i.e., within g or u manifolds) and ~ 1700-2200 s between NSIMs with different inversion symmetries

Bimetallic Pd–Au/Highly Oriented Pyrolytic Graphite Catalysts: from Composition to Pairwise Parahydrogen Addition Selectivity

The model Pd and Au mono- and bi-metallic (Pd–Au) catalysts were prepared using vapor deposition of metals (Au and/or Pd) under ultrahigh vacuum conditions on the defective highly oriented pyrolytic graphite (HOPG) surface. The model catalysts were investigated using the X-ray photoelectron spectroscopy and scanning tunneling microscopy at each stage of the preparation procedure. For the preparation of bimetallic catalysts, different procedures were used to get different structures of PdAu particles (Au_shell–Pd_core or alloyed). All prepared catalysts showed rather narrow particles size distribution with an average particles size in the range of 4–7 nm. Parahydrogen-enhanced nuclear magnetic resonance spectroscopy was used as a tool for the investigation of Pd–Au/HOPG, Pd/HOPG, and Au/HOPG model catalysts in propyne hydrogenation. In contrast to Au sample, Pd, PdAu_alloy, and Au_shell–Pd_core samples were shown to have catalytic activity in propyne conversion, and pairwise hydrogen addition routes were observed. Moreover, bimetallic samples demonstrated the 2- to 5-fold higher activity in pairwise hydrogen addition in comparison to the monometallic Pd sample. It was shown that the structures of bimetallic Pd–Au particles supported on HOPG strongly affected their activities and/or selectivities in propyne hydrogenation reaction: the catalyst with the Au_shell–Pd_core structure demonstrated higher pairwise selectivity than that with the PdAu_alloy structure. Thus, the reported approach can be used as an effective tool for the synergistic effects investigations in hydrogenation reactions over model bimetallic Pd–Au catalysts, where the active component is supported on a planar support