Remarkable Levels of 15N Polarization Delivered through SABRE into Unlabeled Pyridine, Pyrazine, or Metronidazole Enable Single Scan NMR Quantification at the mM Level

Abstract

While many drugs and metabolites contain nitrogen, harnessing their diagnostic ¹⁵N NMR signature for their characterization is underutilized because of inherent detection difficulties. Here, we demonstrate how precise ultralow field signal amplification by reversible exchange (±0.2 mG) in conjunction parahydrogen and an iridium precatalyst of the form IrCl(COD)(NHC) with the coligand d₉-benzylamine allows the naturally abundant ¹⁵N NMR signatures of pyridine, pyrazine, metronidazole, and acetonitrile to be readily detected at 9.4 T in single NMR observations through >50% ¹⁵N polarization levels. These signals allow for rapid and precise reagent quantification via a response that varies linearly over the 2-70 mM concentration range.