Carbon-13 Hyperpolarization of α-Ketocarboxylates with Parahydrogen in Reversible Exchange

Signal Amplification by Reversible Exchange (SABRE) is a relatively simple and fast hyperpolarization technique that has been used to hyperpolarize the α-ketocarboxylate pyruvate, a central metabolite and the leading hyperpolarized MRI contrast agent. In this work, we show that SABRE can readily be extended to hyperpolarize ¹³C nuclei at natural abundance on many other α-ketocarboxylates. Hyperpolarization is observed and optimized on pyruvate (P_13C=17 %) and 2-oxobutyrate (P_13C=25 %) with alkyl chains in the R-group, oxaloacetate (P_13C=11 %) and alpha-ketoglutarate (P_13C=13 %) with carboxylate moieties in the R group, and phenylpyruvate (P_13C=2 %) and phenylglyoxylate (P_13C=2 %) with phenyl rings in the R-group. New catalytically active SABRE binding motifs of the substrates to the hyperpolarization transfer catalyst - particularly for oxaloacetate - are observed. We experimentally explore the connection between temperature and exchange rates for all of these SABRE systems and develop a theoretical kinetic model, which is used to fit the hyperpolarization build-up and decay during SABRE activity.