J Coupling Constants of <1 Hz Enable ¹³C Hyperpolarization of Pyruvate via Reversible Exchange of Parahydrogen

Abstract

Observing pyruvate metabolism in vivo has become a focal point of molecular magnetic resonance imaging. Signal amplification by reversible exchange (SABRE) has recently emerged as a versatile hyperpolarization technique. Tuning of the spin order transfer (SOT) in SABRE is challenging as the small 1 H− 13 C J couplings, in the 13 C-pyruvate case, result in SOT being not readily discernible. We demonstrate an experimental method using frequency-selective excitation of parahydrogen-derived polarization SOT sequence (SEPP-SPINEPT); its application led to up to 5700-fold 13 C signal gain. In this way, we estimated the lifetime of two Ir−pyruvate SABRE complexes alongside the individual probing of eight small 1 H− 13 C J couplings that connect the hydride protons in these complexes to 1-and 2-13 C pyruvate spins, affording values between 0 and 2.69 Hz. Using electronic structure calculations, we define the low-energy structure of the corresponding complexes. Hence, this study demonstrates a novel approach to analyzing the spin topology of short-lived organometallic complexes.

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

“…Compared to conventional hydrogenative PHIP, an advantage of SABRE is that the substrate is chemically not modified during the process. As a result, this approach has substantially broadened the range of compounds that can be polarized using pH 2 . − Moreover, the analyte can be rehyperpolarized multiple times or even continuously, allowing one to obtain useful information about relaxation dynamics, optimize the hyperpolarization process, and perform multidimensional NMR studies − under high atom economy. The SABRE hyperpolarization technique has emerged as a valuable tool for producing HP contrast agents and improving NMR spectroscopic characterizations for various analytes and complex biological mixtures. − …”