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

ABSTRACT: 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.

SUBMITTER: Chukanov NV 

PROVIDER: S-EPMC8172086 | biostudies-literature | 2021 May

REPOSITORIES: biostudies-literature