Toward Continuous Production of Catalyst-Free Hyperpolarized Fluids

Article pubs.acs.org/JPCC

Toward Continuous Production of Catalyst-Free Hyperpolarized Fluids Based on Biphasic and Heterogeneous Hydrogenations with Parahydrogen Kirill V. Kovtunov, Vladimir V. Zhivonitko, Ivan V. Skovpin, Danila A. Barskiy, Oleg G. Salnikov, and Igor V. Koptyug* International Tomography Center SB RAS, 3A Institutskaya Street, 630090 Novosibirsk, Russia, and Novosibirsk State University, 2 Pirogova Street, 630090 Novosibirsk, Russia S Supporting Information *

ABSTRACT: It is demonstrated that hyperpolarized catalyst-free gases can be produced in a gas−liquid biphasic hydrogenation with parahydrogen using a dissolved catalyst and gaseous reactants. The reaction product is shown to return to the gas phase while retaining a substantial level of nuclear spin hyperpolarization, providing a complete separation of the hyperpolarized substance from the catalyst. The approaches based on biphasic and heterogeneous hydrogenations are shown to be suitable for producing hyperpolarization in a continuous mode. Subsequent gas dissolution can be added to yield solutions of hyperpolarized substances. Extension to a broader range of hyperpolarized substances is shown to be possible based on the hydrogenation of liquid vapors.

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INTRODUCTION Hyperpolarization of nuclear spins is one of the hottest topics in modern magnetic resonance because it allows one to boost the sensitivity in spectroscopic and imaging NMR experiments by several orders of magnitude.1−3 Sensitivity issues are of particular importance when one deals with low concentrations and/or small volumes of NMR-active substances. NMR of gases and magnetic resonance imaging (MRI) and spectroscopy (MRS) at high spatial resolution are the common examples of such situations. At present, the hyperpolarization of gases is mostly limited to optical pumping of 129Xe, 3He, 83Kr, and 131 Xe.4−12 Solutions of hyperpolarized substances for MRI are predominantly produced with the dynamic nuclear polarization (DNP) 13 −18 and parahydrogen-induced polarization (PHIP)19−25 techniques. Biomedical in vivo MRI and MRS applications of hyperpolarized substances are among the most demanding and challenging ones, to a significant degree because not every cocktail of fluids produced in a hyperpolarization process can be safely injected in a living organism. In particular, the classical PHIP approach routinely uses transition metal complexes dissolved in a liquid to serve as catalysts for hydrogenation of unsaturated precursors with parahydrogen. While many in vivo experiments are performed without removing the catalyst prior to fluid injection in a lab animal,26−29 advanced biomedical applications clearly require that the catalyst is not present in the fluid at the time of injection. This would also be beneficial for applications of PHIP to the studies of nonliving systems and for a more accurate characterization of the fundamental properties of hyperpolarized molecules not complicated by the presence of an active catalyst. The promising strategies are the removal of the © 2013 American Chemical Society

dissolved metal complex after the homogeneous liquid-phase hydrogenation reaction using appropriate sorbents,30−32 product extraction,33 or the alternative use of heterogeneous catalysts and heterogeneous catalytic processes.34−43 While these approaches have been demonstrated, they still suffer from an insufficient degree of metal complex removal and/or the reduced levels of hyperpolarization. Thus, despite the significant hyperpolarization efficiency achieved with homogeneous PHIP and its recent extension SABRE,25,44−47 the absence of robust and efficient approaches for the production of catalyst-free hyperpolarized fluids is the key obstacle for a much more significant advance in the PHIP technology. Furthermore, the existing approaches based on homogeneous catalytic processes cannot be extended in practice to produce PHIP in a continuous mode because this would consume huge amounts of expensive metal complexes. Thus, the extension of PHIP-based approaches toward the continuous production of hyperpolarization is also hardly possible without the development of efficient catalyst removal and recycling strategies. In this study, we demonstrate an alternative approach to produce catalyst-free hyperpolarized fluids which uses homogeneous catalysts in a biphasic hydrogenation process. It potentially combines the high PHIP efficiency of homogeneous catalysts with the ease of catalyst removal from the reaction products and the advantage of a continuous-flow operation of heterogeneous catalysis. To completely exclude the possibility of catalyst leaching into the product-containing phase, we Received: July 24, 2013 Revised: October 10, 2013 Published: October 11, 2013 22887

dx.doi.org/10.1021/jp407348r | J. Phys. Chem. C 2013, 117, 22887−22893

The Journal of Physical Chemistry C

Article

All biphasic hydrogenations with parahydrogen were performed outside the NMR magnet (the ALTADENA protocol) in a continuous flow mode using one of the two setups shown in Figure S1. The gas coming out of the biphasic reactor was supplied through a Teflon capillary to the 10 mm NMR sample tube residing in the NMR probe during the entire experiment and maintained at 100 °C. In the biphasic hydrogenation of 2,3-dihydrofuran vapor (Figure S6), an extra flask containing liquid 2,3-dihydrofuran was placed upstream of the Buchner flask. Parahydrogen was saturated with the substrate vapor by bubbling it through liquid 2,3dihydrofuran kept at room temperature, and was then supplied to the Buchner flask containing toluene solution of Wilkinson’s catalyst heated to 45 ± 5 °C. Heterogeneous Gas−Solid Hydrogenations. Hydrogenation of 1-octene vapor was performed in the high magnetic field of the NMR spectrometer (the PASADENA experiment). Parahydrogen was first bubbled through liquid 1-octene placed in the Buchner flask as in setup A (Figure S1), except that no catalyst was present in the liquid phase. Then the mixture of H2 and 1-octene vapor was supplied to the 10 mm NMR tube positioned inside the probe of the NMR spectrometer through a Teflon capillary extended to the bottom of the tube where heterogeneous catalyst was placed. In the case of allyl methyl ether hydrogenation, setup A (Figure S1) was also used to saturate parahydrogen with the substrate vapor. However, the reaction in this case was performed outside the NMR magnet (the ALTADENA experiment). The mixture of H2 and substrate vapor was supplied to the reactor comprising a piece of copper tubing with heterogeneous catalyst heated to the required temperature with a tubular furnace. After passing through this reactor, the gaseous mixture was supplied to the 10 mm NMR sample tube residing in the NMR probe via a capillary. The NMR tube was empty in the case when the NMR signal of the gas phase was detected, or contained approximately 3 mL of solvent in the dissolution experiments. For heterogeneous hydrogenation of 1,3-butadiene, the same procedure was used except that the 1:4 mixture of substrate and parahydrogen was supplied directly to the reactor (i.e., setup A was not used). In the experiments with hyperpolarized gas or vapor dissolution, gas bubbling through a solvent in an NMR tube residing in the NMR probe was interrupted for signal detection. Hydrogenation of 1-octene vapor was carried out at 130 °C over 30 mg of catalyst with the flow rate of 3.4 mL/s in the case of Rh/TiO2 catalyst (Figure 4) and 6.8 mL/s in the case of Rh/ Al2O3 catalyst (Figure S7). Butadiene was hydrogenated at 200 °C over 10 mg of Pt/TiO2. The flow rate was 8.5 mL/s. The spectra were recorded in the gas phase and after dissolution in acetone-d6 (Figure 3). Hydrogenation of allyl methyl ether vapor was carried out at 200 °C over 8 mg of Pt/TiO2 catalyst. The flow rate was 1.7 mL/s for the spectrum recorded in the gas phase (Figure S5(1)) and 5.1 mL/s for the spectrum recorded in D2O (Figure S5(2)).

address the gas−liquid biphasic system in which a transition metal complex catalyst resides in the liquid phase while the reactants and products represent the gaseous phase. Gas−liquid biphasic and multiphase processes are well-known in practical catalysis.48−50 The novelty of this work, however, is the demonstration that the reaction product can rapidly return to the gas phase, retaining a significant degree of hyperpolarization after it has left the biphasic region. Thus, this novel approach achieves a clean separation of the reaction products from a catalyst, making it possible to significantly broaden the range of gases that can be hyperpolarized, to produce catalyst-free solutions of hyperpolarized molecules, and holds a potential for producing clean hyperpolarized liquids. Heterogeneous hydrogenation with parahydrogen is used to demonstrate that polarization is preserved upon dissolution of hyperpolarized gases, and to show that hydrogenation of vapors could be a viable approach for producing a broader range of hyperpolarized fluids. It is also shown that, similar to heterogeneous hydrogenations, biphasic processes are inherently suitable for the PHIP production in a continuous mode.

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EXPERIMENTAL SECTION Materials and General Methods. Commercially available hydrogen, propylene, propyne, 1,3-butadiene, 1-octene, 2,3dihydrofuran, and allyl methyl ether were used in the experiments. Metal complexes ([ClRh(PPh3)3], [Rh(PPh2(CH2)4-PPh2)(COD)]BF4, [(COD)Ir(PCy3)(Py)]PF6, [Rh(NBD)2]BF4, [ClRh(P(C6H4SO3Na)3)3]·xH2O were from Sigma-Aldrich. The samples of heterogeneous catalysts (Pt/ TiO2, Rh/Al2O3, Rh/TiO2) were provided by the group of Prof. V.I. Bukhtiyarov (Boreskov Institute of Catalysis, Laboratory of Surface Science, Novosibirsk, Russia). H2 was enriched with parahydrogen by passing it through a FeO(OH) powder (Sigma-Aldrich) maintained at liquid N2 temperature, and the resulting 1:1 ortho-H2: para-H2 mixture was used in all PHIP experiments (referred to below as parahydrogen). All 1H NMR experiments were performed on a 300 MHz Bruker AV 300 NMR spectrometer. In PASADENA experiments, a 45°pulse was used, whereas in ALTADENA experiments a 90°pulse was used for excitation. The number of signal accumulations per spectrum was 1 (Figures 3, S2, S3, S4 (bottom trace), and S5), 8 (Figures 1a, 2, and S4 (top trace)), or 32 (Figures 1b, 4 (bottom trace), S6 and S7). All hydrogenations of gaseous substrates (propylene, propyne, 1,3-butadiene) were performed using a 1:4 mixture of substrate and parahydrogen-enriched H2. All experiments were carried out at atmospheric pressure. Reference experiments were performed after stopping the gas flow. Biphasic Gas−Liquid Hydrogenations. Wilkinson’s catalyst [ClRh(PPh3)3] (45 mg) was dissolved in 6 mL of toluene and used in biphasic hydrogenation of propylene while maintaining solution at 45 ± 5 °C. The gas flow rate was 10 mL/s (Figure 1a). Propylene was also hydrogenated at 25 or 45 ± 5 °C with [ClRh(P(C6H4SO3Na)3)3]·xH2O (34 mg) dissolved in a mixture of water (3 mL) and ethanol (3 mL) at the gas flow rate of 7 mL/s (Figure S4). For propyne hydrogenation, the following solutions were used in different experiments: [Rh(PPh2-(CH2)4-PPh2)(COD)]BF4 (6 mg) in 3 mL of acetone at 25 or 45 ± 5 °C; [(COD)Ir(PCy3)(Py)]PF6 (19 mg) in 3 mL of acetone at 45 ± 5 °C; [Rh(NBD)2]BF4 (9 mg) and PPh3 (13 mg) in 3 mL of acetone 45 ± 5 °C. The gas flow rates were 7 (Figure 2), 8.5 (Figure S2), and 8.5 mL/s (Figure S3), respectively.

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RESULTS AND DISCUSSION Two simple setups were used to perform the reactions (Supporting Information, Figure S1). In setup A, the mixture of gases containing an unsaturated substrate and parahydrogen is bubbled through a homogeneous catalyst solution using a Teflon capillary. The liquid is contained in a Buchner flask, and the gas leaves the flask through the side arm. In setup B, the top part of a Buchner funnel with a glass frit is partially filled with 22888



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Figure 1. (a) 1H NMR spectra acquired in the gas phase during hydrogenation of propylene at ca. 45 °C using the toluene solution of Wilkinson’s catalyst. The spectra were acquired with the flowing gas (bottom trace) or after gas flow was stopped and nuclear spin system returned to equilibrium (top trace). SVap = solvent vapor (toluene). (b) The high-field part of the spectra that were acquired at different gas flow rates indicated in the figure in mL/s.

Table 1. Catalysts Used in the Experiments, Estimated Enhancements for Selected Groups of Protons in the Hydrogenation Products (with the Number of Protons Contributing to the Peak in the Spectrum Acquired under Thermal Equilibrium), and Figures Showing the Corresponding Spectra figure Figure Figure Figure Figure Figure Figure Figure

1a 1a S2 S2 S3 S4 2

substrate

product, # of protons

estimated enhancement

catalyst (precatalyst)

propylene propylene propyne propyne propyne propylene propyne

propane, (−CH3) × 2 propane, (−CH2−) propylene, (−CH=) propane, (−CH3) × 2 propylene, (−CH=) propane, (−CH3) × 2 propylene, (−CH=)

20 ± 2 30 ± 5 90 ± 45 ∼10 74 ± 12 23 ± 2 ≥300

ClRh(PPh3)3 ClRh(PPh3)3 [(COD)Ir(PCy3)(Py)]PF6 [(COD)Ir(PCy3)(Py)]PF6 [Rh(NBD)(PPh3)2]BF4 ([Rh(NBD)2]BF4) ClRh(P(C6H4SO3Na)3)3 ·xH2O [Rh(PPh2-(CH2)4-PPh2)(COD)]BF4

the catalyst solution, and gaseous reactants are supplied from the bottom. Gas bubbles rise through the liquid column, and then the gas leaves the funnel through a thin tube inserted in the rubber plug at the top. In both geometries, the outlet is connected to a capillary that leads the reacted gas to an NMR sample tube positioned in the NMR probe for signal detection. Setup A allows for a more reliable temperature variation of the catalyst solution by placing the flask on a hot plate, while in setup B a heat gun was used for this purpose. Setup B, on the other hand, provides a somewhat higher bubbling efficiency, even though the bubbles are not much smaller. The 1H NMR spectrum was first acquired while a mixture of parahydrogen and propylene was bubbled through the toluene solution of Wilkinson’s catalyst ([ClRh(PPh3)3]) maintained at ca. 45 °C using setup B (Figure 1a, bottom trace). Then the gas flow was stopped, and another spectrum was acquired (Figure 1a, top trace). The NMR signals of the reaction product propane clearly have a much larger absolute intensity when the gas is flowing, with the methylene and the methyl signals showing enhanced absorption and emission, respectively. These signals clearly exhibit a significant degree of hyperpolarization caused by PHIP. The intensities of the propane NMR signals increase as gas flow rate is increased (Figure 1b), reflecting an increasing degree of hyperpolarization of its nuclear spins. The efficiency of the reaction is expected to decrease with the increasing gas flow rate as bubble sizes tend to become somewhat larger, reducing the specific gas/liquid interface area. At the same time, faster delivery of the product from the reactor to the NMR

probe leads to reduced polarization losses. As the observed polarization is still increasing even at the highest flow rates used, we conclude that polarization losses due to the relaxation of nuclear spins are quite significant for the current experimental geometries. Indeed, the T1 time of propane at 1 atm is ca. 0.9 s,43 and is even shorter in gas mixtures containing an excess of H2.51 We also note that when the gas is flowing, the signals of both solvent vapor and propylene (Figures 1a,b) are significantly diminished in intensity as compared to those in the thermally equilibrated spectra because the build-up of equilibrium magnetization upon rapid gas inflow into the NMR tube from outside the magnet is incomplete. This effect, if neglected, can lead to gross errors when one attempts to quantify the signal enhancements provided by hyperpolarization.43 This is why the static gas spectra were used as a reference (see below). The efficiency of the process can be further tuned by varying the nature of the substrate and the catalyst, and by adjusting the reaction conditions (e.g., solvent, solution temperature, etc.). To demonstrate this, we have studied hydrogenation of a triple carbon−carbon bond of propyne using several Rh and Ir complexes. When Crabtree’s catalyst ([(COD)Ir(PCy3)(Py)]PF6; COD = 1,5-cyclooctadiene, Py = pyridine, PCy3 = triscyclohexylphosphine) dissolved in acetone was used, the pronounced hyperpolarization was observed for the methyne (enhanced absorption) and methylene (emission) groups of propylene, the product of semihydrogenation of propyne (Figure S2). In addition, the signals of the product of full hydrogenation, propane, also show some enhancement. In the 22889



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spectrum acquired for the static reaction mixture, the signal of the methyl group of propane can be clearly seen, whereas, the signal of the methyne group of propylene is barely discernible. Similar results were obtained with two Rh catalysts (Wilkinson’s catalyst and [Rh(NBD)(PPh3)2]BF4; NBD = norbornadiene), except that the polarized and the equilibrium signals of propylene were significantly larger (Figure S3). The catalyst [Rh(NBD)(PPh3)2]BF4 was formed in situ from precatalyst [Rh(NBD)2]BF4 and PPh3. The signal enhancement per proton provided by PHIP was estimated by calculating the ratio of the corresponding signals in the spectra of the flowing and the static gas, and multiplying this ratio by the number of protons contributing to the chosen NMR signal to take into account that only one H atom per chemical group in a product molecule comes from parahydrogen. For instance, for the methyl group signal of propane in the spectra of Figure 1a, this gives an enhancement of ca. 3.5 × 6 ≈ 20, as six protons of the two methyl groups contribute to this 1H NMR signal. Other enhancement factors are summarized in Table 1. One can see that in the majority of cases, the enhancement factors are on the order of 20−50. If one converts these signal enhancements to nuclear spin polarization levels, the values obtained will be about 2 orders of magnitude lower than polarization levels of 20−50% reported earlier for homogeneous hydrogenations with parahydrogen.29,32,52,53 At the same time, for most catalysts a substantial product formation is observed despite the use of the very simple reactors. In fact, the moderate levels of signal enhancement and an efficient substrate-to-product conversion observed for most catalysts are quite comparable with the values we often observe when authentic supported metal catalysts are used in such experiments.41−43,54,55 In addition, in this work, an activation period at the elevated temperature under the reaction mixture atmosphere was usually required to observe hyperpolarization, which sometimes amounted to tens of minutes. All these facts suggest that in the presence of H2, the complexes used may get reduced, at least partially, to produce nanoparticulate suspensions. Indeed, it is well-known that many transition metal complexes are easily converted to metal nanoparticles even under mild reaction conditions in the presence of H2,56,57 so much so that the heterogeneous nature of many ‘homogeneous’ catalytic processes is either proven or suspected.56 Another possibility is that the readily available metal complexes used in this work are suboptimal in terms of the reaction mechanism for the use in homogeneous hydrogenations in solution. This issue will be addressed in detail in future studies, but in any case, the use of custom-synthesized metal complexes52,53 is expected to give much better results in biphasic hydrogenations. The situation was very different with the bidentate cationic complex [Rh(PPh2-(CH2)4-PPh2)(COD)]BF4 (Figure 2). The increase in solution temperature from RT to ca. 45 °C increased the intensity of hyperpolarized signals of propylene significantly, the trend that was also observed for other catalysts used in this work. Contrary to other homogeneous catalysts, however, no traces of the products could be observed in the NMR spectrum acquired after the gas flow was stopped (Figure 2, top trace). Despite that, the intensity of polarized signals was very large. From these results we estimated the lower bound for the enhancement factor as ≥300. This was done by modeling the spectra and determining the minimum signal intensity for which the signal is still observable provided that the noise level

Figure 2. 1H NMR spectra acquired in the gas phase during hydrogenation of propyne using an acetone solution of the bidentate cationic complex [Rh(PPh2-(CH2)4-PPh2)(COD)]BF4. The spectra were acquired with the flowing gas (bottom and middle traces) or after gas flow was stopped and nuclear spin system returned to equilibrium (top trace). The catalyst solution was maintained at 25 (bottom trace) or 45 °C (middle and top traces). The broad signal labeled ‘H2’ belongs to orthohydrogen. SVap = solvent vapor (acetone); this signal is clipped in the top spectrum.

matches that of the experimental spectra. The actual enhancement factor can be even larger, especially considering the fact that some polarization is lost due to relaxation effects, but a more accurate estimate is not possible at this time. Nevertheless, much lower conversions combined with a much higher signal enhancement observed for this catalyst allow us to tentatively conclude that in this particular case polarization is generated predominantly by a homogeneous Rh complex. This is in agreement with the literature reports31,58 that owing to the specifics of the reaction mechanism, [Rh(diene)(diphosphine)]+ complexes are able to produce significantly larger PHIP effects because the catalyst first coordinates an unsaturated substrate, in contrast to complexes such as Wilkinson’s catalyst which activate H2 first. One of the features of all acquired spectra is the presence of the NMR signals of the vapor of the solvent used (see, e.g., Figures 1,2, and Figure S2). Solvent vapors may be irrelevant in certain applications, or could be removed using a cold trap. Aqueous solutions of water-soluble metal complexes have demonstrated high reactant-to-product conversion combined with a high PHIP efficiency in potential biomedical applications.29,32,52,53 To show that it is possible to produce hyperpolarized products using water-based biphasic hydrogenation, we used a solution of the water-soluble analog of the Wilkinson’s catalyst, [ClRh(P(C6H4SO3Na)3)3], in a 1:1 water:ethanol mixture. The PHIP effects were observed successfully in the hydrogenation of propylene to propane (Figure S4). Given that the catalyst, the reaction conditions and the substrate are anything but optimal, the results obtained are quite promising. For certain applications it would be useful to have hyperpolarized substances as solutions rather than gases. This can be achieved by dissolving the hyperpolarized gaseous product in an appropriate solvent. To monitor the behavior of hyperpolarized gas upon dissolution and to experimentally verify that hyperpolarization can indeed survive this gassolution phase transfer, we used a heterogeneously catalyzed hydrogenation of 1,3-butadiene with parahydrogen. Hydro22890



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TiO2 or Rh/Al2O3), and the reaction products were detected in the gas phase by 1H NMR (PASADENA experiment). As Figure 4 and Figure S7 demonstrate, octane produced in the

genation was performed outside the NMR magnet, and then the gas stream containing hyperpolarized butane was bubbled through acetone-d6 residing in the sample tube in the NMR magnet. The enhanced 1H NMR signals of the methyl and methylene groups of dissolved hyperpolarized butane can be easily spotted in the acquired spectrum (Figure 3), demonstrat-

Figure 4. 1H NMR spectrum acquired during gas-phase hydrogenation of 1-octene vapor over Rh/TiO2 catalyst. The gas-phase spectrum of 1octene is shown at the top.

reaction exhibits a pronounced PHIP effect. Another example is the heterogeneous hydrogenation of allyl methyl ether vapor in an ALTADENA experiment mentioned in the preceding paragraph (Figure S5). These results demonstrate that hydrogenation of liquid vapors is quite feasible as a means of expanding the range of hyperpolarizable molecules. Addition of the dissolution stage demonstrated above will yield clean solutions of hyperpolarized molecules. Yet another possibility is the rapid condensation of hyperpolarized vapors (Figure S7) to produce highly concentrated hyperpolarized liquids, which in principle can be performed in a continuous way, similar to the continuous production of hyperpolarized gases demonstrated above. We also note that 1-octene (the reactant) in the gas phase (Figure 4) exhibits the characteristic antiphase polarization patterns as well. This could be the result of various accompanying catalytic processes, e.g., dehydrogenation, isomerization, and hydrogen exchange. Similar observations have been reported previously for propylene.59

Figure 3. 1H NMR spectra acquired during gas-phase hydrogenation of 1,3-butadiene over Pt/TiO2 catalyst. The spectra were acquired in the gas phase (1,2) or after dissolution of the gaseous mixture in acetone-d6 (3,4) for flowing gas (1), for static gas after nuclear spin system returned to equilibrium (2), immediately after gas dissolution (3) or after dissolution and spin system equilibration (4). Solv = solvent (residual H atoms in liquid acetone-d6).

ing the viability of the proposed approach. Comparison of the signal enhancements for butane in the gas and liquid phases showed that it retained no less than 30% of polarization upon dissolution. A similar experiment with the hydrogenation of allyl methyl ether successfully demonstrated the possibility to use dissolution to produce aqueous solutions of hyperpolarized substances (Figure S5). Finally, the biphasic approach described above is quite likely not limited to the hyperpolarization of only those compounds that under normal conditions exist as gases, but should be applicable to liquid vapors as well. The simple experimental setups used in this study would be inappropriate for such processes. Nevertheless, by saturating H2 with a substrate vapor and passing it through the catalyst solution, we were able to observe the hydrogenation reaction products in the outcoming gas stream. As an example, Figure S6 shows the results obtained for biphasic hydrogenation of 2,3-dihydrofuran vapor, demonstrating that the reaction product (tetrahydrofuran) does escape in substantial quantities into the gas phase after reaction. To observe PHIP effects in these experiments, more sophisticated designs would be required, but successful observation of the product in the gas stream shows that such extension of the proposed approach should be feasible. Here, we demonstrate an alternative possibility to produce hyperpolarized molecules in a vapor phase, based on the use of a heterogeneous hydrogenation. To this end, parahydrogen was saturated with 1-octene vapor and then supplied to an NMR tube residing in the NMR probe and containing heterogeneous catalyst (Rh/

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CONCLUSIONS Exploration of nuclear spin hyperpolarization in NMR calls for the development of improved hyperpolarization techniques. In this work, a new general strategy for using parahydrogeninduced polarization to produce hyperpolarized catalyst-free substances was introduced. In its current implementation, it is based on a gas−liquid biphasic hydrogenation with parahydrogen using a dissolved catalyst and gaseous reactants. It was demonstrated experimentally that reaction products can return to the gas phase rapidly enough to retain a significant degree of hyperpolarization. In addition to achieving a clean separation of the hyperpolarized reaction products from a catalyst, this novel approach significantly expands the range of gases that can be produced in a highly hyperpolarized state. Furthermore, similar to heterogeneous hydrogenations, the biphasic approach is suitable for a continuous production of hyperpolarized substances. With appropriate modifications, it is expected that this hyperpolarization approach may be extended from gases to liquid vapors. With the use of heterogeneous catalysts, it was demonstrated that vapors of unsaturated compounds can be hyperpolarized, and that hyperpolarization 22891



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of vapors and gases largely survives a dissolution process, paving the way to the production of clean hyperpolarized solutions.

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ASSOCIATED CONTENT

* Supporting Information S

Additional spectra. This material is available free of charge via the Internet at http://pubs.acs.org.

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AUTHOR INFORMATION

Corresponding Author

*E-mail: [email protected]. Author Contributions

The manuscript was written through contributions of all authors. All authors have given approval to the final version of the manuscript. Notes

The authors declare no competing financial interest.

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ACKNOWLEDGMENTS

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REFERENCES

This work was partially supported by grants from RFBR (## 11-03-00248-a, 12-03-00403-a, 12-03-31386-mol-a), RAS (# 5.1.1), SB RAS (## 60, 61, 57, 122), the program of support of leading scientific schools (#NSh-2429.2012.3), the Council on Grants of the President of the Russian Federation (MK4391.2013.3), and the program of the Russian Government to support leading scientists (# 11.G34.31.0045). We thank Prof. V. I. Bukhtiyarov and his group (Boreskov Institute of Catalysis, Laboratory of Surface Science, Novosibirsk, Russia) for providing the samples of heterogeneous catalysts used in this work.

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