Hyperpolarising Pyruvate through Signal Amplification by Reversible Exchange (SABRE)

Abstract

Hyperpolarisation methods that premagnetise agents such as pyruvate are currently receiving significant attention because they produce sensitivity gains that allowd isease tracking and interrogation of cellular metabolism by magnetic resonance.Here,wecommunicate how signal amplification by reversible exchange (SABRE) can providestrong 13 Cpyruvate signal enhancements in seconds through the formation of the novel polarisation transfer catalyst [Ir(H) 2 (h 2 -pyruvate)-(DMSO)(IMes)].B yh arnessing SABRE, strong signals for [1-13 C]-and [2-13 C]pyruvate in addition to along-lived singlet state in the [1,2-13 C 2 ]form are readily created;the latter can be observed five minutes after the initial hyperpolarisation step. We also demonstrate how this development may help with future studies of chemical reactivity.

“Direct” 13C Hyperpolarization of 13C‐Acetate by MicroTesla NMR Signal Amplification by Reversible Exchange (SABRE)

“…Given the direct nature of the SABRE mechanism employed here, there is no fundamental reason why resulting heteronuclear polarization enhancements cannot ultimately approach those already achieved via SABRE‐SHEATH in other substrate classes . Additionally, significantly longer hyperpolarization lifetimes may be achievable in doubly labelled acetate through population of 13 C– 13 C singlet states, which very recently have been shown to extend the lifetime of HP 1,2‐ 13 C‐pyruvate . In principle, such states are more easily populated via SABRE than d‐DNP.…”

“…[23,34] Additionally,s ignificantly longer hyperpolarization lifetimes may be achievable in doubly labelled acetate through population of 13 C- 13 Cs inglet states, [33] which very recently have been shown to extend the lifetime of HP 1,2-13 C-pyruvate. [28] In principle,s uch states are more easily populated via SABRE than d-DNP.S uch improvements, combined with recent demonstrations of SABRE under aqueous [34] and heterogeneous catalytic conditions, [35] as well as novel catalyst-filtration/separation methods, [24,36] bode well for ultimate translation of SABRE-based approaches for avariety of promising biological and biomedical applications.…”

“…), Duckett and co‐workers recently showed that a wide range of species—including carboxylic acid derivatives—can also be hyperpolarized by “relaying” spin order via exchangeable HP protons of auxiliary amine species; the potential disadvantage of this approach is that it can tend to spread the hyperpolarization pool over a relatively large spin bath of exchangeable protons, leading to polarization level reduction. To circumvent such limitations, pyruvate was very recently hyperpolarized directly via SABRE, where both carbonyl and carboxyl pyruvate sites interact with the Ir catalyst . However, the requirement of two ligating sites may limit this new approach to α‐keto carboxylates.…”

“…To circumvent such limitations,pyruvate was very recently hyperpolarized directly via SABRE, where both carbonyl and carboxyl pyruvate sites interact with the Ir catalyst. [28] However,t he requirement of two ligating sites may limit this new approach to a-keto carboxylates.S eparately,w er ecently showed that HP 13 C-acetate could be SABRE-hyperpolarized via ad ifferent strategy: [29] First, polarization is spin-relayed [30] through the covalent heteronuclear spin network of as ynthesized "double agent" (comprised of a 13 C-acetyl moiety bound to acatalyst-binding 15 N 2 -imidazolic moiety) within am icro-Tesla field;H P 13 Cacetate/acetic acid (and 15 N 2 -imidazole) may then be released on demand via hydrolytic cleavage. [29] Here,w es how that it is possible to achieve 13 Ch yperpolarization of 1-13 C-acetate under SABRE-SHEATH conditions with enhancements up to % 100-fold, without need for polarization to be relayed via either an exchangeable proton from an auxiliary species,o racovalent spin network within acleavable substrate.Moreover,itisshown that the effect is consistent with amechanism of "direct" transfer of spin order from parahydrogen to 13 Cs pins of acetate weakly bound to the catalyst, under conditions of fast exchange with respect to the 13 Cacetate resonance;however,the underlying relaxation dynamics at microtesla fields are found to alter the optimal matching conditions from those of the the traditional SABRE-SHEATH picture.…”

Chloroquine and Lopinavir (COVID-19 Drug Candidates) Signal Amplification by Reversible Exchange

“…Of several methods to hyperpolarize drugs, the para-hydrogen based signal amplification by reversible exchange (SABRE) method is a promising tool for hyperpolarization of several key structures with nitrogen. Furthermore, its polarization could be transferred in real time from protons to other isotopes such as 13 Several great recent studies of producing hyperpolarized drugs or metabolites [16][17][18][19][20] , including pharmacokinetics using SABRE 21 , confirm that such a study would widen its application in this era, when scientific solutions are the only way to conquer this disaster. Therefore, a hyperpolarization study using SABRE may be a good and key start to applying MRI scanning by using hyperpolarized chloroquine/lopinavir in the future.…”