Journal article
Isaiah Adelabu, Md Raduanul H Chowdhury, Shiraz Nantogma, Clementinah Oladun, Firoz Ahmed, L. Stilgenbauer, M. Sadagurski, T. Theis, B. Goodson, E. Chekmenev
Metabolites, 2023
Metabolites, 2023
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APA
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Adelabu, I., Chowdhury, M. R. H., Nantogma, S., Oladun, C., Ahmed, F., Stilgenbauer, L., … Chekmenev, E. (2023). Efficient SABRE-SHEATH Hyperpolarization of Potent Branched-Chain-Amino-Acid Metabolic Probe [1-13C]ketoisocaproate. Metabolites.
Chicago/Turabian
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Adelabu, Isaiah, Md Raduanul H Chowdhury, Shiraz Nantogma, Clementinah Oladun, Firoz Ahmed, L. Stilgenbauer, M. Sadagurski, T. Theis, B. Goodson, and E. Chekmenev. “Efficient SABRE-SHEATH Hyperpolarization of Potent Branched-Chain-Amino-Acid Metabolic Probe [1-13C]Ketoisocaproate.” Metabolites (2023).
MLA
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Adelabu, Isaiah, et al. “Efficient SABRE-SHEATH Hyperpolarization of Potent Branched-Chain-Amino-Acid Metabolic Probe [1-13C]Ketoisocaproate.” Metabolites, 2023.
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@article{isaiah2023a,
title = {Efficient SABRE-SHEATH Hyperpolarization of Potent Branched-Chain-Amino-Acid Metabolic Probe [1-13C]ketoisocaproate},
year = {2023},
journal = {Metabolites},
author = {Adelabu, Isaiah and Chowdhury, Md Raduanul H and Nantogma, Shiraz and Oladun, Clementinah and Ahmed, Firoz and Stilgenbauer, L. and Sadagurski, M. and Theis, T. and Goodson, B. and Chekmenev, E.}
}
Abstract
Efficient 13C hyperpolarization of ketoisocaproate is demonstrated in natural isotopic abundance and [1-13C]enriched forms via SABRE-SHEATH (Signal Amplification By Reversible Exchange in SHield Enables Alignment Transfer to Heteronuclei). Parahydrogen, as the source of nuclear spin order, and ketoisocaproate undergo simultaneous chemical exchange with an Ir-IMes-based hexacoordinate complex in CD3OD. SABRE-SHEATH enables spontaneous polarization transfer from parahydrogen-derived hydrides to the 13C nucleus of transiently bound ketoisocaproate. 13C polarization values of up to 18% are achieved at the 1-13C site in 1 min in the liquid state at 30 mM substrate concentration. The efficient polarization build-up becomes possible due to favorable relaxation dynamics. Specifically, the exponential build-up time constant (14.3 ± 0.6 s) is substantially lower than the corresponding polarization decay time constant (22.8 ± 1.2 s) at the optimum polarization transfer field (0.4 microtesla) and temperature (10 °C). The experiments with natural abundance ketoisocaproate revealed polarization level on the 13C-2 site of less than 1%—i.e., one order of magnitude lower than that of the 1-13C site—which is only partially due to more-efficient relaxation dynamics in sub-microtesla fields. We rationalize the overall much lower 13C-2 polarization efficiency in part by less favorable catalyst-binding dynamics of the C-2 site. Pilot SABRE experiments at pH 4.0 (acidified sample) versus pH 6.1 (unaltered sodium [1-13C]ketoisocaproate) reveal substantial modulation of SABRE-SHEATH processes by pH, warranting future systematic pH titration studies of ketoisocaproate, as well as other structurally similar ketocarboxylate motifs including pyruvate and alpha-ketoglutarate, with the overarching goal of maximizing 13C polarization levels in these potent molecular probes. Finally, we also report on the pilot post-mortem use of HP [1-13C]ketoisocaproate in a euthanized mouse, demonstrating that SABRE-hyperpolarized 13C contrast agents hold promise for future metabolic studies.