Real-Time NMR Quantification of Paramagnetic Species during Chemical Reactions

Paramagnetic species, such as molecular oxygen, play crucial roles in chemical reactions, yet their concentrations are difficult to measure in real time. Nuclear magnetic resonance (NMR) spectroscopy is powerful for monitoring chemical reactions, but direct quantification requires a NMR-active nucleus with relatively sharp signals, which is not available for many paramagnetic species, like oxygen. ¹H longitudinal relaxation rates (R₁) are sensitive to paramagnetic species and can be used to follow concentrations, but traditional relaxation measurements are often too slow for monitoring kinetics. Here, we introduce paramagnetic species tracking via relaxation-based concentration estimation (PARATRACE), a simple NMR approach that converts routine solvent signals into in situ probes of paramagnetic species. The method exploits the sensitivity of solvent proton R₁ to paramagnetic species by monitoring solvent signal integrals in the regime of partial relaxation between successive scans. Changes in R₁ and, thus, in paramagnetic species can be followed while other reactants are simultaneously monitored at no detriment to time resolution. Using the photodegradation of betamethasone as a model system, we show that oxygen depletion can be quantitatively tracked, in parallel with the main reaction species, throughout the reaction. This approach turns conventional NMR acquisition into a real-time reporter of the paramagnetic environment.