NMR Signal Enhancement for Hyperpolarized Fluids Continuously Generated in Hydrogenation Reactions with Parahydrogen

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 ¹H 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

Synthesis of Unsaturated Precursors for Parahydrogen-Induced Polarization and Molecular Imaging of 1-¹³C‑Acetates and 1-¹³C‑Pyruvates via Side Arm Hydrogenation

Hyperpolarized forms of 1-¹³C-acetates and 1-¹³C-pyruvates are used as diagnostic contrast agents for molecular imaging of many diseases and disorders. Here, we report the synthetic preparation of 1-¹³C 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 1-¹³C-acetates and 1-¹³C-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 ¹³C nucleus via magnetic field cycling procedure to achieve hyperpolarization of ¹³C nuclear spins. This work reports the synthesis of PHIP-SAH precursors: vinyl 1-¹³C-acetate (55% yield), allyl 1-¹³C-acetate (70% yield), propargyl 1-¹³C-acetate (45% yield), allyl 1-¹³C-pyruvate (60% yield), and propargyl 1-¹³C-pyruvate (35% yield). Feasibility of PHIP-SAH ¹³C hyperpolarization was verified by ¹³C NMR spectroscopy: hyperpolarized allyl 1-¹³C-pyruvate was produced from propargyl 1-¹³C-pyruvate with ¹³C polarization of ∼3.2% in CD₃OD and ∼0.7% in D₂O. ¹³C magnetic resonance imaging is demonstrated with hyperpolarized 1-¹³C-pyruvate in aqueous medium

C–H Activation on Co,O Sites: Isolated Surface Sites versus Molecular Analogs

The activation and conversion of hydrocarbons is one of the most important challenges in chemistry. Transition-metal ions (V, Cr, Fe, Co, etc.) isolated on silica surfaces are known to catalyze such processes. The mechanisms of these processes are currently unknown but are thought to involve C–H activation as the rate-determining step. Here, we synthesize well-defined Co­(II) ions on a silica surface using a metal siloxide precursor followed by thermal treatment under vacuum at 500 °C. We show that these isolated Co­(II) sites are catalysts for a number of hydrocarbon conversion reactions, such as the dehydrogenation of propane, the hydrogenation of propene, and the trimerization of terminal alkynes. We then investigate the mechanisms of these processes using kinetics, kinetic isotope effects, isotopic labeling experiments, parahydrogen induced polarization (PHIP) NMR, and comparison with a molecular analog. The data are consistent with all of these reactions occurring by a common mechanism, involving heterolytic C–H or H–H activation via a 1,2 addition across a Co–O bond

C–H Activation on Co,O Sites: Isolated Surface Sites versus Molecular Analogs

The activation and conversion of hydrocarbons is one of the most important challenges in chemistry. Transition-metal ions (V, Cr, Fe, Co, etc.) isolated on silica surfaces are known to catalyze such processes. The mechanisms of these processes are currently unknown but are thought to involve C–H activation as the rate-determining step. Here, we synthesize well-defined Co­(II) ions on a silica surface using a metal siloxide precursor followed by thermal treatment under vacuum at 500 °C. We show that these isolated Co­(II) sites are catalysts for a number of hydrocarbon conversion reactions, such as the dehydrogenation of propane, the hydrogenation of propene, and the trimerization of terminal alkynes. We then investigate the mechanisms of these processes using kinetics, kinetic isotope effects, isotopic labeling experiments, parahydrogen induced polarization (PHIP) NMR, and comparison with a molecular analog. The data are consistent with all of these reactions occurring by a common mechanism, involving heterolytic C–H or H–H activation via a 1,2 addition across a Co–O bond

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

Facile Removal of Homogeneous SABRE Catalysts for Purifying Hyperpolarized Metronidazole, a Potential Hypoxia Sensor

Here, we report a simple and effective method to remove IrIMes homogeneous polarization transfer catalysts from solutions where NMR signal amplification by reversible exchange (SABRE) has been performed, while leaving intact the substrate’s hyperpolarized state. Following microtesla SABRE hyperpolarization of ¹⁵N spins in metronidazole, addition of SiO₂ microparticles functionalized with 3-mercaptopropyl or 2-mercaptoethyl ethyl sulfide moieties provides removal of the catalyst from solution well within the hyperpolarization decay time at 0.3 T (<i>T</i>₁ > 3 min) and enabling transfer to 9.4 T for detection of enhanced ¹⁵N signals in the absence of catalyst within the NMR detection region. Successful catalyst removal from solution is supported by the inability to “rehyperpolarize” ¹⁵N spins in subsequent attempts, as well as by ¹H NMR and inductively coupled plasma mass spectrometry. Record-high ¹⁵N nuclear polarization of up to ∼34% was achieved, corresponding to >100 000-fold enhancement at 9.4 T (or >320,000-fold enhancement at 3.0 T), and approximately 5/6th of the ¹⁵N hyperpolarization is retained after ∼20 s long purification procedure. Taken together, these results help pave the way for future studies, involving in vivo molecular imaging using agents hyperpolarized via rapid and inexpensive parahydrogen-based methods

NMR SLIC Sensing of Hydrogenation Reactions Using Parahydrogen in Low Magnetic Fields

Parahydrogen-induced polarization (PHIP) is an NMR hyperpolarization technique that increases nuclear spin polarization by orders of magnitude, and it is particularly well-suited to study hydrogenation reactions. However, the use of high-field NMR spectroscopy is not always possible, especially in the context of potential industrial-scale reactor applications. On the other hand, the direct low-field NMR detection of reaction products with enhanced nuclear spin polarization is challenging due to near complete signal cancellation from nascent parahydrogen protons. We show that hydrogenation products prepared by PHIP can be irradiated with weak (on the order of spin–spin couplings of a few hertz) alternating magnetic field (called Spin-Lock Induced Crossing or SLIC) and consequently efficiently detected at low magnetic field (e.g., 0.05 T used here) using examples of several types of organic molecules containing a vinyl moiety. The detected hyperpolarized signals from several reaction products at tens of millimolar concentrations were enhanced by 10000-fold, producing NMR signals an order of magnitude greater than the background signal from protonated solvents

X–H Bond Activation on Cr(III),O Sites (X = R, H): Key Steps in Dehydrogenation and Hydrogenation Processes

We synthesized isolated Cr­(III) sites on SiO₂−Al₂O₃ and Al₂O₃ by grafting and subsequent controlled thermal treatment of Cr­(OSi­(O^tBu)₃)₃(THF)₂ and Cr­(Al­(OⁱPr)₄)₃ on alumina. CrO_<i>x</i>/Al₂O₃ was obtained from incipient wetness impregnation of Al₂O₃ with CrO₃ in H₂O followed by calcination, as carried out for the synthesis of industrial Cr-based dehydrogenation catalysts. These materials were characterized by IR, EPR, XAS, and by the adsorption of the probe molecules CO and pyridine, and the results were compared to previously reported isolated Cr­(III)/SiO₂. All of these materials were active in propane dehydrogenation at 550 °C, where higher TOFs were obtained for Cr­(III)/SiO₂-Al₂O₃ and Cr­(III)/Al₂O₃ than for CrO_<i>x</i>/Al₂O₃ and Cr­(III)/SiO₂. For mechanistic studies the reverse reaction, propene hydrogenation, was studied. Here, the order of reactivity was opposite that of dehydrogenation, with CrO_<i>x</i>/Al₂O₃ and Cr­(III)/SiO₂ being more active in hydrogenation than Cr­(III)/SiO₂-Al₂O₃ and Cr­(III)/Al₂O₃. Kinetic analysis and labeling studies with D₂ showed that the rate law is in all cases first order in H₂ partial pressure but had different dependence on propene partial pressure from catalyst to catalyst. We found small normal kinetic isotope effects of 1 ≤ KIE ≤ 2, activation enthalpies up to 40 kJ mol^–1, and large negative activation entropies between −100 and −194 J K^–1 mol^–1 for the different Cr catalysts. We also performed parahydrogen-induced polarization (PHIP) experiments, which showed that H₂ addition to propene proceeds, at least in part, via a pairwise mechanism. The experimental data for propene hydrogenation suggests adsorption/desorption pre-equilibria of H₂ (or D₂) and propene followed by H₂ activation and insertion of propene. DFT computations for propane dehydrogenation and propene hydrogenation on Cr­(III) on a periodic alumina model show that a mechanism involving X–H activation (X = R, H) is energetically feasible with activation enthalpies and entropies that are comparable to the experimentally determined values

X–H Bond Activation on Cr(III),O Sites (X = R, H): Key Steps in Dehydrogenation and Hydrogenation Processes

We synthesized isolated Cr­(III) sites on SiO₂−Al₂O₃ and Al₂O₃ by grafting and subsequent controlled thermal treatment of Cr­(OSi­(O^tBu)₃)₃(THF)₂ and Cr­(Al­(OⁱPr)₄)₃ on alumina. CrO_<i>x</i>/Al₂O₃ was obtained from incipient wetness impregnation of Al₂O₃ with CrO₃ in H₂O followed by calcination, as carried out for the synthesis of industrial Cr-based dehydrogenation catalysts. These materials were characterized by IR, EPR, XAS, and by the adsorption of the probe molecules CO and pyridine, and the results were compared to previously reported isolated Cr­(III)/SiO₂. All of these materials were active in propane dehydrogenation at 550 °C, where higher TOFs were obtained for Cr­(III)/SiO₂-Al₂O₃ and Cr­(III)/Al₂O₃ than for CrO_<i>x</i>/Al₂O₃ and Cr­(III)/SiO₂. For mechanistic studies the reverse reaction, propene hydrogenation, was studied. Here, the order of reactivity was opposite that of dehydrogenation, with CrO_<i>x</i>/Al₂O₃ and Cr­(III)/SiO₂ being more active in hydrogenation than Cr­(III)/SiO₂-Al₂O₃ and Cr­(III)/Al₂O₃. Kinetic analysis and labeling studies with D₂ showed that the rate law is in all cases first order in H₂ partial pressure but had different dependence on propene partial pressure from catalyst to catalyst. We found small normal kinetic isotope effects of 1 ≤ KIE ≤ 2, activation enthalpies up to 40 kJ mol^–1, and large negative activation entropies between −100 and −194 J K^–1 mol^–1 for the different Cr catalysts. We also performed parahydrogen-induced polarization (PHIP) experiments, which showed that H₂ addition to propene proceeds, at least in part, via a pairwise mechanism. The experimental data for propene hydrogenation suggests adsorption/desorption pre-equilibria of H₂ (or D₂) and propene followed by H₂ activation and insertion of propene. DFT computations for propane dehydrogenation and propene hydrogenation on Cr­(III) on a periodic alumina model show that a mechanism involving X–H activation (X = R, H) is energetically feasible with activation enthalpies and entropies that are comparable to the experimentally determined values

Hydrogenation of Unsaturated Six-Membered Cyclic Hydrocarbons Studied by the Parahydrogen-Induced Polarization Technique

Parahydrogen-induced polarization (PHIP) is an efficient technique for mechanistic investigations of homogeneous and heterogeneous catalytic hydrogenations. Herein, heterogeneous gas phase hydrogenation of six-membered cyclic hydrocarbons (benzene, toluene, cyclohexene, 1,3-cyclohexadiene and 1,4-cyclohexadiene) over Rh/TiO₂, Pd/TiO₂, and Pt/TiO₂ catalysts was studied using PHIP. As expected, cyclohexene hydrogenation led to the formation of cyclohexane which because of its symmetry should not exhibit any PHIP effects. However, the presence of ¹³C nuclei at natural abundance (1.1%) breaks molecular symmetry, resulting in the observation of ¹³C satellite signals exhibiting PHIP effects in the ¹H NMR spectra. In experiments with cyclohexene, the reactant’s NMR signals were also polarized, demonstrating the possibility of cyclohexene dehydrogenation to 1,3-cyclohexadiene and subsequent hydrogenation to cyclohexene. In the hydrogenation of 1,3-cyclohexadiene and 1,4-cyclohexadiene, all NMR signals of cyclohexene exhibited PHIP effects, implying migration of CC bonds in 1,4-cyclohexadiene and cyclohexene. At the same time, upon hydrogenation of benzene and toluene the reaction products were those with saturated cycles exclusively (cyclohexane and methylcyclohexane, respectively), and their NMR signals were not polarized. The absence of PHIP effects for arene hydrogenation can be explained by a difference in the reaction mechanism compared to cyclohexane and cyclohexadienes hydrogenations, along with the larger extent to which hydrogen atoms undergo migration on the catalyst surface facilitated by lower catalyst coverage with an adsorbed substrate in case of arenes