Isotropic mixing in liquid-state Overhauser dynamic nuclear polarization

Establishing carbon-carbon connectivities by NMR at natural isotope abundance is intrinsically challenging due to the low sensitivity of ¹³C-¹³C correlation experiments. Conventional strategies rely on polarization transfer from light nuclei, i.e. ¹H or ¹⁹F, to enhance sensitivity, rendering systems devoid of such nuclei particularly difficult to study. We recently developed an NMR-optimized Overhauser-effect dynamic nuclear polarization (OE-DNP) setup that provides signal enhancements of up to two orders of magnitude for carbons which are chlorinated or iodinated, but lack ¹H and ¹⁹F, in small organic molecules dissolved in organic solvent. Here, we demonstrate that in such systems, hyperpolarization can be coherently transferred between ¹³C nuclei using 1D and pseudo-2D isotropic mixing (IM) experiments. This allows ¹³C-¹³C satellite signals to be detected, at natural isotopic abundance, from which one-bond carbon-carbon scalar coupling (¹J_CC) constants can be read off. These OE-DNP-enhanced IM experiments are shown to even outperform conventional 1D INADEQUATE experiments in these challenging systems. Furthermore, we demonstrate that IM can be used as a preparatory block in OE-DNP-enhanced multiple pulse NMR experiments, as exemplified by a 2D OE-DNP-IM-HETCOR sequence. Finally, the transfer of polarization in hyperpolarized systems is described using both an approximate analytical treatment, based on the product operator formalism, and numerical simulations employing an effective Hamiltonian theory.