¹⁵ N Reaction Monitoring at Low and Inhomogeneous Magnetic Fields Enabled by Hyperpolarization with Parahydrogen

The combination of hyperpolarization methods with low and inhomogeneous fields promises to expand the application of nuclear magnetic resonance (NMR) to fields that nowadays are not standard. Reducing the magnetic field strengths and homogeneity requirements opens the door to a wide variety of magnet designs that can allow for monitoring chemical reactions in the benchtop or even larger reactors. In this work, we propose a method to monitor ¹⁵N chemical reactions at low and inhomogeneous fields based on parahydrogen-induced polarization. The concept was demonstrated at a magnetic field of 66 mT and 81 ppm inhomogeneity. Specifically, we measured the conversion of ¹⁵N-boronobenzyl-2-styrylpyridinium (¹⁵N-BBSP) to ¹⁵N-2-styrylpyridin (¹⁵N-SP). This enables the detection of H₂O₂ with high sensitivity and selectivity, exhibiting a significant chemical shift difference of 88.4 ppm, when ¹⁵N-SP is obtained after a base-assisted 1,6 elimination/rearrangement. The long T₁ of ¹⁵N-BBSP at low magnetic fields (194 s at 100 mT) exemplifies the potential of hyperpolarized ¹⁵N for low field applications. We envision the implementation of our methods for studying chemical reactions in benchtop devices, drug screening, investigating biological systems in their native environments, preclinical research and contrast development for low-field and portable magnetic resonance imaging (MRI).