Approximately 98% parahydrogen gas was synthesized by pulsing ambient research grade hydrogen gas at 14 bar (200 psi) into a catalyst-filled (iron oxide) copper chamber held at 14 K using a previously described semiautomated parahydrogen generator.15 (link) Fresh batches of parahydrogen were collected in 10 L aluminum storage tanks (14745-SHF-GNOS, Holley, KY), used without Teflon lining or additional modification.
The preparation of PASADENA9 ,10 (link) precursor aqueous solutions was similar to those previously described16 (link) with the exception that water was used in place of 99.8% D2O as a solvent. 320 μmol (0.180 g) of the disodium salt of 1,4-bis[(phenyl-3-propanesulfonate)phosphine]butane (#717347, Sigma-Aldrich-Isotec, OH) was combined with 100 mL of H2O in a 1 L flask. This ambient solution was then degassed with a rotary evaporator (model R-215 equipped with V-710 pump, Buchi, New Castle, DE) fitted with an N2(g) input, by decrementing the onboard pressure slowly to avoid boiling, from 70 to 25 mbar over approximately 10 min. The rhodium(I) catalyst, bis(norbornadiene) rhodium(I) tetrafluoroborate (0.10 g, 0.27 mmol, 45-0230, CAS 36620-11-8, Strem Chemicals, MA) was dissolved in 7 mL of acetone and was added dropwise to the phosphine ligand solution to limit undesirable precipitation. After the prior degassing procedure was repeated, this catalyst solution was mixed with 2-hydroxyethyl acrylate-1-13C,2,3,3-d3 (HEA, 97% chemical purity, 99 atom % 13C, 98 atom % D (20 mg, 0.16 mmol, Sigma-Aldrich, 676071) in a 150 mL square bottle (431430, Corning Life Sciences, NY).
Solutions containing unsaturated precursor molecules with bidentate Rh(I) catalyst prepared as described above were then connected to a previously described automated parahydrogen polarizer,16 (link) equipped with a dual-tuned 1H/13C coil.17 (link) Briefly, the chemical reaction was pulse programmed with a commercial NMR console (model KEA2, Magritek, Wellington, New Zealand) to synchronize chemical reaction parameters, decoupling fields, polarization transfer sequences, and detection of NMR signals. PASADENA precursors were sprayed remotely into a plastic (polysulfone) reactor located within a 47.5 mT static magnetic field. The external solution was equilibrated at 65 °C prior to spraying, and 16.5 bar (240 psi) nitrogen gas was used to inject this heated PASADENA precursor solution into a pressurized atmosphere of 7 bar (100 psi) parahydrogen. Immediately following injection, proton continuous wave decoupling was applied at a frequency of 2.02 MHz (B0 = 47.5 mT) with a magnitude of 5 kHz. This decoupling radio frequency field was maintained for 4 s to freeze the parahydrogen spin ensemble while the hydrogenation reaction went to completion.14 (link)The pulse sequences for transferring polarization were applied immediately after continuous wave decoupling was turned off (Figure 1 ). For the HEP molecule, the t1, t2, t3, and t4 intervals were 9.75, 58.47, 36.20, and 28.28 ms, respectively, calculated by inverting the density matrix expressions above (see Theory) assuming a proton–proton coupling of 7.57 Hz, and a carbon–proton scalar coupling asymmetry of 12.86 Hz.14 (link) The actual couplings could vary somewhat from these values depending on pH and specific attributes of the polarization process such as temperature and pressure. After parahydrogen spin order was transferred to net magnetization, a single free induction decay was acquired (90–acquire) on the carbon channel with 512 points at a receiver bandwidth of 5 kHz, for a digital resolution of ~10 Hz per point.
The preparation of PASADENA9 ,10 (link) precursor aqueous solutions was similar to those previously described16 (link) with the exception that water was used in place of 99.8% D2O as a solvent. 320 μmol (0.180 g) of the disodium salt of 1,4-bis[(phenyl-3-propanesulfonate)phosphine]butane (#717347, Sigma-Aldrich-Isotec, OH) was combined with 100 mL of H2O in a 1 L flask. This ambient solution was then degassed with a rotary evaporator (model R-215 equipped with V-710 pump, Buchi, New Castle, DE) fitted with an N2(g) input, by decrementing the onboard pressure slowly to avoid boiling, from 70 to 25 mbar over approximately 10 min. The rhodium(I) catalyst, bis(norbornadiene) rhodium(I) tetrafluoroborate (0.10 g, 0.27 mmol, 45-0230, CAS 36620-11-8, Strem Chemicals, MA) was dissolved in 7 mL of acetone and was added dropwise to the phosphine ligand solution to limit undesirable precipitation. After the prior degassing procedure was repeated, this catalyst solution was mixed with 2-hydroxyethyl acrylate-1-13C,2,3,3-d3 (HEA, 97% chemical purity, 99 atom % 13C, 98 atom % D (20 mg, 0.16 mmol, Sigma-Aldrich, 676071) in a 150 mL square bottle (431430, Corning Life Sciences, NY).
Solutions containing unsaturated precursor molecules with bidentate Rh(I) catalyst prepared as described above were then connected to a previously described automated parahydrogen polarizer,16 (link) equipped with a dual-tuned 1H/13C coil.17 (link) Briefly, the chemical reaction was pulse programmed with a commercial NMR console (model KEA2, Magritek, Wellington, New Zealand) to synchronize chemical reaction parameters, decoupling fields, polarization transfer sequences, and detection of NMR signals. PASADENA precursors were sprayed remotely into a plastic (polysulfone) reactor located within a 47.5 mT static magnetic field. The external solution was equilibrated at 65 °C prior to spraying, and 16.5 bar (240 psi) nitrogen gas was used to inject this heated PASADENA precursor solution into a pressurized atmosphere of 7 bar (100 psi) parahydrogen. Immediately following injection, proton continuous wave decoupling was applied at a frequency of 2.02 MHz (B0 = 47.5 mT) with a magnitude of 5 kHz. This decoupling radio frequency field was maintained for 4 s to freeze the parahydrogen spin ensemble while the hydrogenation reaction went to completion.14 (link)The pulse sequences for transferring polarization were applied immediately after continuous wave decoupling was turned off (
