Synthesis and ¹⁵ N NMR Signal Amplification by Reversible Exchange of [ ¹⁵ N]Dalfampridine at Microtesla Magnetic Fields

Signal Amplification by Reversible Exchange (SABRE) technique enables nuclear spin hyperpolarization of wide range of compounds using parahydrogen. Here we present the synthetic approach to prepare 15 N-labeled [15 N]dalfampridine (4-amino[15 N]pyridine) utilized as a drug to reduce the symptoms of multiple sclerosis. The synthesized compound was hyperpolarized using SABRE at microtesla magnetic fields (SABRE-SHEATH technique) with up to 2.0 % 15 N polarization. The 7-hour-long activation of SABRE pre-catalyst [Ir(IMes)(COD)Cl] in the presence of [15 N]dalfampridine can be remedied by the use of pyridine co-ligand for catalyst activation while retaining the 15 N polarization levels of [15 N]dalfampridine. The effects of experimental conditions such as polarization transfer magnetic field, temperature, concentration, parahydrogen flow rate and pressure on 15 N polarization levels of free and equatorial catalyst-bound [15 N]dalfampridine were investigated. Moreover, we studied 15 N polarization build-up and decay at magnetic field of less than 0.04 μT as well as 15 N polarization decay at the Earth's magnetic field and at 1.4 T.