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 C nuclei at natural abundance on many other α-ketocarboxylates. Hyperpolarization is observed and optimized on pyruvate (P=17 %) and 2-oxobutyrate (P=25 %) with alkyl chains in the R-group, oxaloacetate (P=11 %) and alpha-ketoglutarate (P=13 %) with carboxylate moieties in the R group, and phenylpyruvate (P=2 %) and phenylglyoxylate (P=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.

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