Quasi-Resonance Signal Amplification by Reversible Exchange.

Abstract

Here we present the feasibility of NMR signal amplification by reversible exchange (SABRE) using radio frequency irradiation at low magnetic field (0.05 T) in the regime where the chemical shifts of free and catalyst-bound species are similar. In SABRE, the 15N-containing substrate and parahydrogen perform simultaneous chemical exchange on an iridium hexacoordinate complex. A shaped spin-lock induced crossing (SLIC) radio frequency pulse sequence followed by a delay is applied at quasi-resonance (QUASR) conditions of 15N spins of a 15N-enriched substrate. As a result of this pulse sequence application, 15N z-magnetization is created from the spin order of parahydrogen-derived hyperpolarized hydrides. The repetition of the pulse sequence block consisting of a shaped radio frequency pulse and the delay leads to the buildup of 15N magnetization. The modulation of this effect by the irradiation frequency, pulse duration and amplitude, delay duration, and number of pumping cycles was demonstrated. Pyridine-15N, acetonitrile-15N, and metronidazole-15N2-13C2 substrates were studied representing three classes of compounds (five- and six-membered heterocycles and nitrile), showing the wide applicability of the technique. Metronidazole-15N2-13C2 is an FDA-approved antibiotic that can be injected in large quantities, promising noninvasive and accurate hypoxia sensing. The 15N hyperpolarization levels attained with QUASR-SABRE on metronidazole-15N2-13C2 were more than 2-fold greater than those with SABRE-SHEATH (SABRE in shield enables alignment transfer to heteronuclei), demonstrating that QUASR-SABRE can deliver significantly more efficient means of SABRE hyperpolarization.