SABRE Acethydrazide as a Co-Substrate Agent for Quantitative Analysis of Submicromolar N-Heterocyclic Compounds Using Parahydrogen Hyperpolarization

초록

Signal amplification by reversible exchange (SABRE) hyperpolarization is a well-known method for enhancing nuclear magnetic resonance (NMR) signals by transferring para-hydrogen-derived polarization to the analyte of interest. However, due to inherent sensitivity limitations, detecting analyte signals at micromolar (mu M) or lower concentrations remains challenging. This study proposes acethydrazide (ACH) as a novel co-substrate, which significantly improves SABRE hyperpolarization efficiency and enables the detection of aromatic N-heterocycles at submicromolar concentrations. ACH enhances signal amplification by stabilizing iridium catalysts through the formation of a pincer complex, as confirmed by non-hydrogenative parahydrogen-induced polarization (nhPHIP) experiments and density functional theory (DFT) calculations. Notably, at the optimal concentration ratio of iridium catalyst:analytes:ACH (1:1:6.5), detection of aromatic N-heterocycles at concentrations below 1.0 mu M can be achieved within a single scan using a 400 MHz NMR spectrometer. The enhancement factor and signal-to-noise ratio of the nicotinamide H2-free proton are 422-fold and 2.52 au, respectively, at 0.75 mu M using 3 bar of 60% parahydrogen. The ability to detect analytes at a micromolar concentration using SABRE with this new co-substrate expands its potential for biological and industrial applications.

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