Direct 15N–13C Heteronuclear Correlation Spectroscopy Enhanced by Spin-Lock-Induced Crossing and Reversible Parahydrogen Exchange

Abstract

Direct observation of 15N–13C heteronuclear correlations by conventional thermal NMR is limited by the low sensitivity of both nuclei. To overcome this limitation, we use low-field spin-lock-induced crossing signal amplification by reversible exchange (SLIC-SABRE) hyperpolarization to perform 15N–13C correlation spectroscopy in 15N-labeled small molecules containing 13C at natural abundance (1.1%). In SLIC-SABRE, polarization is transferred from parahydrogen to the substrate during their reversible interactions with an Ir-based complex. By tailoring the hyperpolarized spin order generated by SLIC-SABRE and the subsequent detection pathway, complementary one- and two-dimensional experiments with 15N and 13C detection provide site-specific connectivities, resolved 15N–13C J-couplings, and 13C-induced isotope shifts of the 15N resonances. The approach is demonstrated for a selenadiazole derivative and metronidazole, with two-dimensional 15N–13C correlation spectra acquired in approximately 40 min. Together, these results demonstrate the potential of SLIC-SABRE for rapid, site-resolved heteronuclear correlation spectroscopy.