TY - JOUR

T1 - Modeling Ligand Exchange Kinetics in Iridium Complexes Catalyzing SABRE Nuclear Spin Hyperpolarization

AU - Salnikov, Oleg G.

AU - Assaf, Charbel D.

AU - Yi, Anna P.

AU - Duckett, Simon B.

AU - Chekmenev, Eduard Y.

AU - Hövener, Jan Bernd

AU - Koptyug, Igor V.

AU - Pravdivtsev, Andrey N.

N1 - A.N.P., C.D.A., and J.-B.H. acknowledge funding from German Federal Ministry of Education and Research (BMBF) within the framework of the e:Med research and funding concept (01ZX1915C), DFG (PR 1868/3-1, PR 1868/5-1, HO-4602/2-2, HO-4602/3, GRK2154-2019, 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). O.G.S. and A.P.Y. thank the Russian Science Foundation (Grant 21-73-10105) for the support of experimental exchange rates and relaxation measurements and the development of exchange models. E.C. is thankful for the funding support by NSF CHE-1904780. S.B.D. thanks UK Research and Innovation (UKRI) under the UK government\u2019s Horizon Europe funding guarantee [Grant Number EP/X023672/1].

PY - 2024/7/23

Y1 - 2024/7/23

N2 - Large signal enhancements can be obtained for NMR analytes using the process of nuclear spin hyperpolarization. Organometallic complexes that bind parahydrogen can themselves become hyperpolarized. Moreover, if parahydrogen and a to-be-hyperpolarized analyte undergo chemical exchange with the organometallic complex it is possible to catalytically sensitize the detection of the analyte via hyperpolarization transfer through spin-spin coupling in this organometallic complex. This process is called Signal Amplification By Reversible Exchange (SABRE). Signal intensity gains of several orders of magnitude can thus be created for various compounds in seconds. The chemical exchange processes play a defining role in controlling the efficiency of SABRE because the lifetime of the complex must match the spin-spin couplings. Here, we show how analyte dissociation rates in the key model substrates pyridine (the simplest six-membered heterocycle), 4-aminopyridine (a drug), and nicotinamide (an essential vitamin biomolecule) can be examined. This is achieved for the most widely employed SABRE motif that is based on IrIMes-derived catalysts by 1H 1D and 2D exchange NMR spectroscopy techniques. Several kinetic models are evaluated for their accuracy and simplicity. By incorporating variable temperature analysis, the data yields key enthalpies and entropies of activation that are critical for understanding the underlying SABRE catalyst properties and subsequently optimizing behavior through rational chemical design. While several studies of chemical exchange in SABRE have been reported, this work also aims to establish a toolkit on how to quantify chemical exchange in SABRE and ensure that data can be compared reliably.

AB - Large signal enhancements can be obtained for NMR analytes using the process of nuclear spin hyperpolarization. Organometallic complexes that bind parahydrogen can themselves become hyperpolarized. Moreover, if parahydrogen and a to-be-hyperpolarized analyte undergo chemical exchange with the organometallic complex it is possible to catalytically sensitize the detection of the analyte via hyperpolarization transfer through spin-spin coupling in this organometallic complex. This process is called Signal Amplification By Reversible Exchange (SABRE). Signal intensity gains of several orders of magnitude can thus be created for various compounds in seconds. The chemical exchange processes play a defining role in controlling the efficiency of SABRE because the lifetime of the complex must match the spin-spin couplings. Here, we show how analyte dissociation rates in the key model substrates pyridine (the simplest six-membered heterocycle), 4-aminopyridine (a drug), and nicotinamide (an essential vitamin biomolecule) can be examined. This is achieved for the most widely employed SABRE motif that is based on IrIMes-derived catalysts by 1H 1D and 2D exchange NMR spectroscopy techniques. Several kinetic models are evaluated for their accuracy and simplicity. By incorporating variable temperature analysis, the data yields key enthalpies and entropies of activation that are critical for understanding the underlying SABRE catalyst properties and subsequently optimizing behavior through rational chemical design. While several studies of chemical exchange in SABRE have been reported, this work also aims to establish a toolkit on how to quantify chemical exchange in SABRE and ensure that data can be compared reliably.

UR - https://www.mendeley.com/catalogue/2ea02fd6-1bba-3c3f-99c9-b44095429616/

U2 - 10.1021/acs.analchem.4c01374

DO - 10.1021/acs.analchem.4c01374

M3 - Article

C2 - 38976810

VL - 96

SP - 11790

EP - 11799

JO - Analytical Chemistry

JF - Analytical Chemistry

SN - 0003-2700

IS - 29

ER -