Mechanistic insights into chemical exchange during the signal amplification by reversible exchange sensitization of pyruvate

Abstract

Abstract Signal amplification by reversible exchange (SABRE) is a nuclear spin hyperpolarization technique in which the transient interaction of parahydrogen (pH 2 ) and a target substrate with an iridium complex leads to polarization of the substrate. SABRE enables direct hyperpolarization of the substrate without chemical modification, enabling rapid polarization buildup within seconds under mild conditions. Here, we use a parahydrogen-enhanced, spin-selective nuclear magnetic resonance method to investigate pyruvate binding, which is combined with exchange-model fitting and density functional theory calculations. Our study reveals several key findings that reshape the current understanding of SABRE. First, we observe that intramolecular hydrogen exchange of the hydrides occurs faster than pyruvate or H 2 loss. Second, we discover a distinct stable [Ir(H) 2 (IMes)(κ 1 -pyr)(DMSO) 2 ] complex. Finally, the results suggest a potential role of counterions (here Na + ) in Ir-pyruvate binding. Insights into complex kinetics and distributions as a function of temperature, [DMSO], [pyruvate], and hydrogen pressure are presented. The methods demonstrated here, exemplified by SABRE, provide a framework that is expected to guide future research in the field.