TY - JOUR

T1 - Heteronuclear Parahydrogen-Induced Hyperpolarization via Side Arm Hydrogenation

AU - Salnikov, Oleg G.

AU - Chukanov, Nikita V.

AU - Pravdivtsev, Andrey N.

AU - Burueva, Dudari B.

AU - Sviyazov, Sergey V.

AU - Them, Kolja

AU - Hövener, Jan Bernd

AU - Koptyug, Igor V.

N1 - O.G.S., N.V.C., D.B.B., and S.V.S. thank the Russian Science Foundation (grant 24-73-10093) for the support of preparation of all sections of this review except Sections 3 and 5. A.N.P., K.T., and J.B.H. acknowledge support from German Federal Ministry of Education and Research (BMBF) within the framework of the e:Med research and funding concept (01ZX1915C, 03WIR6208A hyperquant) and DFG (555951950, 527469039, 469366436, HO-4602/2-2, HO-4602/3, HO-4602/4, EXC2167, FOR5042, TRR287). MOIN CC was founded by a grant from the European Regional Development Fund (ERDF) and the Zukunftsprogramm Wirtschaft of Schleswig-Holstein (Project no. 122-09-053).

PY - 2025/4/10

Y1 - 2025/4/10

N2 - Nuclear spin hyperpolarization dramatically enhances the sensitivity of nuclear magnetic resonance spectroscopy and imaging. Hyperpolarization of biomolecules (e.g., pyruvate) is of particular interest as it allows one to follow their metabolism, providing a diagnostic tool for various pathologies, including cancer. In this regard, the hyperpolarization of 13C nuclei is especially beneficial due to its typically relatively long hyperpolarization lifetime and the absence of a background signal. Parahydrogen-induced polarization (PHIP) is arguably the most affordable hyperpolarization technique. PHIP exploits the pairwise addition of parahydrogen to an unsaturated substrate. This sets limitations on the range of compounds amenable to direct PHIP hyperpolarization. The range of molecules that can be hyperpolarized with PHIP significantly expanded in 2015 when PHIP by means of side arm hydrogenation (PHIP-SAH) was introduced. Herein, parahydrogen is added to an unsaturated alcoholic moiety of an ester followed by polarization transfer to carboxylate 13C nuclei with a subsequent side arm cleavage. In this review, the recent advances in PHIP-SAH are discussed, including the synthetic methodology to produce isotopically labeled precursors, peculiarities of pairwise addition of parahydrogen to PHIP-SAH precursors, polarization transfer approaches, hyperpolarization lifetime, side arm cleavage, purification of hyperpolarized solution, and, finally, in vitro and in vivo applications.

AB - Nuclear spin hyperpolarization dramatically enhances the sensitivity of nuclear magnetic resonance spectroscopy and imaging. Hyperpolarization of biomolecules (e.g., pyruvate) is of particular interest as it allows one to follow their metabolism, providing a diagnostic tool for various pathologies, including cancer. In this regard, the hyperpolarization of 13C nuclei is especially beneficial due to its typically relatively long hyperpolarization lifetime and the absence of a background signal. Parahydrogen-induced polarization (PHIP) is arguably the most affordable hyperpolarization technique. PHIP exploits the pairwise addition of parahydrogen to an unsaturated substrate. This sets limitations on the range of compounds amenable to direct PHIP hyperpolarization. The range of molecules that can be hyperpolarized with PHIP significantly expanded in 2015 when PHIP by means of side arm hydrogenation (PHIP-SAH) was introduced. Herein, parahydrogen is added to an unsaturated alcoholic moiety of an ester followed by polarization transfer to carboxylate 13C nuclei with a subsequent side arm cleavage. In this review, the recent advances in PHIP-SAH are discussed, including the synthetic methodology to produce isotopically labeled precursors, peculiarities of pairwise addition of parahydrogen to PHIP-SAH precursors, polarization transfer approaches, hyperpolarization lifetime, side arm cleavage, purification of hyperpolarized solution, and, finally, in vitro and in vivo applications.

KW - hydrogenation

KW - hyperpolarization

KW - magnetic resonance imaging

KW - nuclear magnetic resonance spectroscopy

KW - parahydrogen-induced polarization

UR - https://www.mendeley.com/catalogue/af824c74-b5de-3c90-9b76-6479287b4cf1/

UR - https://www.scopus.com/record/display.uri?eid=2-s2.0-105003889744&origin=inward&txGid=e509e633ea764201f2beb68c967a900f

U2 - 10.1002/cphc.202401119

DO - 10.1002/cphc.202401119

M3 - Review article

C2 - 40211662

SP - e2401119

JO - ChemPhysChem

JF - ChemPhysChem

SN - 1439-4235

ER -