SABRE-Enhanced NMR Spectroscopy for Analyte Detection

The SABRE enhanced ¹H NMR response was detected on either a 400 MHz Bruker Avance III using a BBI probe or a 43 MHz (1 T) Magritek Spinsolve Carbon benchtop NMR spectrometer. The SABRE samples contained 26 mM of the target analyte and 5.2 mM of the SABRE pre-catalyst in the form [IrCl(COD)(NHC)] (where COD = 1,5 cyclooctadiene) where the N-heterocyclic carbene (NHC) was either 1,3-bis(2,4,6-trimethylphenyl)-imidazol-2-ylidine (IMes) or 1,3-bis(2,4,6-tris(methyl-d₃)-4,5-d₂-phenyl)-imidazol-2-ylidine (d₂₂-IMes) (see Fig. 1). The target analytes were: 4-methylpyridine, pyridine and methyl-4,6-d₂-nicotinate and the solvent was methanol-d₄ (Fig. 1). Both of the catalysts and the methyl-4,6-d₂-nicotinate were synthesised in-house,45 (link) the analytes 4-methylpyridine and pyridine were purchased from Sigma-Aldrich. For each sample, a 7 mL bulk solution containing catalyst, analyte and solvent was prepared and 0.6 mL was subsequently distributed into ten different NMR tubes, each fitted with a Young's valve and degassed using a 3-stage freeze–pump–thaw-method in a bath of dry ice and acetone. The SABRE catalyst was activated by adding 4 bar p-H₂ to the headspace of the NMR tube and shaking vigorously for ten seconds. This was repeated six times and then the sample was left inside the NMR spectrometer for a further ten minutes to ensure full activation of each sample. Once activated, a single-scan thermal ¹H NMR spectrum was acquired as a reference for the SABRE enhancement factor calculation. For each subsequent SABRE experiment, the head-space of the NMR tube was evacuated and then charged with 4 bar p-H₂ at the desired enrichment level and shaken for 10 seconds in a handheld Halbach array with a static field of 63 G before being manually transferred to the NMR spectrometer for detection.46 (link) The sample transfer time was 3.5 ± 0.5 s and each measurement was repeated 5 times.
For the SABRE-Relay method, samples were made by first preparing a 7 mL bulk solution containing 5.2 mM of the pre-catalyst [IrCl(COD)(IMes)] in dichloromethane-d₂ (DCM-d₂) in a 10 mm diameter NMR tube fitted with a Young's valve. The sample was degassed using a 3-stage freeze–thaw–pump process using liquid nitrogen. Ammonia gas was introduced to the head-space of the NMR tube and dipped in liquid nitrogen quickly to promote condensation, and the tube was sealed and subsequently shaken vigorously for 10 seconds to promote dissolution of the ammonia. The amount of ammonia in solution was quantified using liquid state ¹H NMR to be 42 ± 2 mM (see ESI† for full details). 26 mM (13.6 μL) of 1-propanol was added to the NMR tube and the solution was de-gassed using a 3-stage freeze–pump–thaw method with liquid nitrogen. The 7 mL bulk solution was distributed into ten different NMR tubes for analysis (each 0.6 mL). The SABRE catalyst was activated by adding 4 bar of H₂ to the headspace of the NMR tube, which was then shaken for ten seconds and left overnight.
In order to calculate the enhancement factor and subsequently the polarisation, a single scan non-hyperpolarised ¹H NMR spectrum was acquired with the same settings as the subsequent SABRE-enhanced detection. The enhancement factors, ε, were then determined by taking a ratio of the thermal and hyperpolarised integrals as in eqn (7). Polarisation, P, was calculated by scaling the enhancement factor to the thermal polarisation level in the detection field using eqn (8), where γ is the gyromagnetic ratio, B₀ is the detection field, T is the sample temperature, ħ is the reduced Planck's constant, and k_B is Boltzmann's constant.