Optimisation of pyruvate hyperpolarisation using SABRE by tuning the active magnetisation transfer catalyst.

Ben J Tickner,Olga Semenova,Simon B Duckett,Peter J Rayner,Wissam Iali,Adrian C Whitwood

doi:10.1039/c9cy02498k

Abstract

Hyperpolarisation techniques such as signal amplification by reversible exchange (SABRE) can deliver NMR signals several orders of magnitude larger than those derived under Boltzmann conditions. SABRE is able to catalytically transfer latent magnetisation from para-hydrogen to a substrate in reversible exchange via temporary associations with an iridium complex. SABRE has recently been applied to the hyperpolarisation of pyruvate, a substrate often used in many in vivo MRI studies. In this work, we seek to optimise the pyruvate-13C2 signal gains delivered through SABRE by fine tuning the properties of the active polarisation transfer catalyst. We present a detailed study of the effects of varying the carbene and sulfoxide ligands on the formation and behaviour of the active [Ir(H)2(η2-pyruvate)(sulfoxide)(NHC)] catalyst to produce a rationale for achieving high pyruvate signal gains in a cheap and refreshable manner. This optimisation approach allows us to achieve signal enhancements of 2140 and 2125-fold for the 1-13C and 2-13C sites respectively of sodium pyruvate-1,2-[13C2].

Highlights

Hyperpolarisation techniques such as signal amplification by reversible exchange (SABRE) can deliver Nuclear magnetic resonance (NMR) signals several orders of magnitude larger than those derived under Boltzmann conditions
We seek to optimise the pyruvate-13C2 signal gains delivered through SABRE by fine tuning the properties of the active polarisation transfer catalyst
We present a detailed study of the effects of varying the carbene and sulfoxide ligands on the formation and behaviour of the active [IrIJH)2IJη2-pyruvate)IJsulfoxide)IJNHC)] catalyst to produce a rationale for achieving high pyruvate signal gains in a cheap and refreshable manner

Summary

Introduction

Frequency of the electron at very low temperatures (1–2 K).[4,5,6] Rapid heating of such solids generates materials that yield MR signal enhancements in solution of up to 5 orders of magnitude.[5,6] This approach has been applied to the production of hyperpolarised biomolecules such as pyruvate,[7,8,9,10,11,12,13,14] succinate,[15,16] and fumarate[17,18] which are injected and detected in vivo alongside their metabolic byproducts. It has since been reported that by using appropriate stabilising ligands, SABRE can hyperpolarise pyruvate in a low cost, fast, and reversible fashion that does not involve the technologically demanding equipment of DNP, or the multiple steps of PHIP-SAH.[39] This is possible due to the formation of the polarisation transfer catalyst [IrIJH)2IJη2pyruvate)IJDMSO)IJIMes)] (where IMes = 1,3-bisIJ2,4,6-trimethylphenyl)imidazol-2-ylidene) when solutions of [IrClIJCOD)IJIMes)] (1a) (where COD = cis,cis-1,5-cyclooctadiene), DMSO and sodium pyruvate in methanol-d4 or 70 : 30 mixtures of D2O and ethanol-d6 are activated with 3 bar of H2 We explore the properties of the active catalyst by varying the identity of both sulfoxide and NHC ligand to produce a rationale for achieving high 13C pyruvate NMR signal enhancements using SABRE

Results and discussion

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Conclusions