Synthesis and 15N NMR Signal Amplification by Reversible Exchange of [15N]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 ¹⁵N-labeled ¹⁵N]dalfampridine (4-amino¹⁵N]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 % ¹⁵N polarization. The 7-hour-long activation of SABRE pre-catalyst Ir(IMes)(COD)Cl] in the presence of ¹⁵N]dalfampridine can be remedied by the use of pyridine co-ligand for catalyst activation while retaining the ¹⁵N polarization levels of ¹⁵N]dalfampridine. The effects of experimental conditions such as polarization transfer magnetic field, temperature, concentration, parahydrogen flow rate and pressure on ¹⁵N polarization levels of free and equatorial catalyst-bound ¹⁵N]dalfampridine were investigated. Moreover, we studied ¹⁵N polarization build-up and decay at magnetic field of less than 0.04 μT as well as ¹⁵N polarization decay at the Earth's magnetic field and at 1.4 T.