Dataset Information

Quantifying the effects of quadrupolar sinks via¹⁵N relaxation dynamics in metronidazoles hyperpolarized via SABRE-SHEATH.

ABSTRACT: ¹⁵N spin-lattice relaxation dynamics in metronidazole-¹⁵N₃ and metronidazole-¹⁵N₂ isotopologues are studied for rational design of ¹⁵N-enriched biomolecules for signal amplification by reversible exchange in microtesla fields. ¹⁵N relaxation dynamics mapping reveals the deleterious effects of interactions with the polarization transfer catalyst and a quadrupolar ¹⁴N nucleus within the spin-relayed ¹⁵N-¹⁵N network.

SUBMITTER: Birchall JR

PROVIDER: S-EPMC7441520 | biostudies-literature | 2020 Aug

REPOSITORIES: biostudies-literature

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Quantifying the effects of quadrupolar sinks via15N relaxation dynamics in metronidazoles hyperpolarized via SABRE-SHEATH.

Birchall Jonathan R JR Kabir Mohammad S H MSH Salnikov Oleg G OG Chukanov Nikita V NV Svyatova Alexandra A Kovtunov Kirill V KV Koptyug Igor V IV Gelovani Juri G JG Goodson Boyd M BM Pham Wellington W Chekmenev Eduard Y EY

Chemical communications (Cambridge, England) 20200714 64

15N spin-lattice relaxation dynamics in metronidazole-15N3 and metronidazole-15N2 isotopologues are studied for rational design of 15N-enriched biomolecules for signal amplification by reversible exchange in microtesla fields. 15N relaxation dynamics mapping reveals the deleterious effects of interactions with the polarization transfer catalyst and a quadrupolar 14N nucleus within the spin-relayed 15</su ...[more]

PMID: 32661534

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Project description:α-Ketoglutarate is a key biomolecule involved in a number of metabolic pathways─most notably the TCA cycle. Abnormal α-ketoglutarate metabolism has also been linked with cancer. Here, isotopic labeling was employed to synthesize [1-13C,5-12C,D4]α-ketoglutarate with the future goal of utilizing its [1-13C]-hyperpolarized state for real-time metabolic imaging of α-ketoglutarate analytes and its downstream metabolites in vivo. The signal amplification by reversible exchange in shield enables alignment transfer to heteronuclei (SABRE-SHEATH) hyperpolarization technique was used to create 9.7% [1-13C] polarization in 1 minute in this isotopologue. The efficient 13C hyperpolarization, which utilizes parahydrogen as the source of nuclear spin order, is also supported by favorable relaxation dynamics at 0.4 μT field (the optimal polarization transfer field): the exponential 13C polarization buildup constant Tb is 11.0 ± 0.4 s whereas the 13C polarization decay constant T1 is 18.5 ± 0.7 s. An even higher 13C polarization value of 17.3% was achieved using natural-abundance α-ketoglutarate disodium salt, with overall similar relaxation dynamics at 0.4 μT field, indicating that substrate deuteration leads only to a slight increase (∼1.2-fold) in the relaxation rates for 13C nuclei separated by three chemical bonds. Instead, the gain in polarization (natural abundance versus [1-13C]-labeled) is rationalized through the smaller heat capacity of the "spin bath" comprising available 13C spins that must be hyperpolarized by the same number of parahydrogen present in each sample, in line with previous 15N SABRE-SHEATH studies. Remarkably, the C-2 carbon was not hyperpolarized in both α-ketoglutarate isotopologues studied; this observation is in sharp contrast with previously reported SABRE-SHEATH pyruvate studies, indicating that the catalyst-binding dynamics of C-2 in α-ketoglutarate differ from that in pyruvate. We also demonstrate that 13C spectroscopic characterization of α-ketoglutarate and pyruvate analytes can be performed at natural 13C abundance with an estimated detection limit of 80 micromolar concentration × *%P13C. All in all, the fundamental studies reported here enable a wide range of research communities with a new hyperpolarized contrast agent potentially useful for metabolic imaging of brain function, cancer, and other metabolically challenging diseases.

Dataset Information

Quantifying the effects of quadrupolar sinks via¹⁵N relaxation dynamics in metronidazoles hyperpolarized via SABRE-SHEATH.

Publications

Quantifying the effects of quadrupolar sinks via<sup>15</sup>N relaxation dynamics in metronidazoles hyperpolarized via SABRE-SHEATH.

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