Integrating Binding Thermodynamics and Relaxation for Evaluating Substrate-Dependent SABRE Performance

Signal amplification by reversible exchange (SABRE), a parahydrogen-based hyperpolarization technique, stands out for its operational accessibility and exceptional sensitivity enhancement. However, the structure-dependent mechanisms underlying hyperpolarization efficiency remain elusive, hindering targeted optimization. Herein, we investigated the relationship between substrate structure and SABRE hyperpolarization efficiency by probing coordination thermodynamics between pyridine/pyrazine derivatives and iridium catalyst precursors using ¹H NMR, 2D diffusion-ordered spectroscopy (DOSY), and T₁ relaxation measurements. We found that substrates exhibiting large coordination equilibrium constants (K_eq) and decreased self-diffusion coefficients upon ligation to the catalyst generally showed higher signal enhancement. Further hyperpolarization on a mixture of four pyridine derivatives confirmed a direct correlation between signal enhancement and K_eq magnitudes, i.e., the higher the K_eq, the stronger the SABRE enhancement. Furthermore, the rapid spin relaxation of the substrate, as evidenced by shortened T₁ values upon ligation to the Ir catalyst, contributed to suboptimal hyperpolarization performance. These findings provide useful experimental insight into substrate-dependent SABRE performance by revealing the combined roles of substrate coordination to the catalyst precursor and relaxation-mediated polarization retention.