Halogen-Bond-Mediated ¹³C Overhauser Dynamic Nuclear Polarization at 9.4 T

Overhauser dynamic nuclear polarization (OE-DNP) is capable of enhancing solution ¹³C NMR signals of analytes by 1-2 orders of magnitude through spin polarization transfer from paramagnetic polarizing agents, usually nitroxide radicals, at magnetic fields relevant for high-resolution NMR spectroscopy (≳9 T). While some halogen atoms have been revealed to mediate OE-DNP on adjacent ¹³C, methods of promoting OE-DNP through halogen bond (XB) design were not well-understood. Here we investigate OE-DNP of selected halogenated compounds by tuning their XB strengths to the nitroxide radicals through molecular design. Up to 10-fold boosts in OE-DNP enhancements were achieved by increasing the analyte XB donor strength in selected iodinated and brominated derivatives. Furthermore, we observed strong correlation between OE-DNP performance and XB properties for compounds sharing similar XB binding sites. Our results suggest new possibilities for designing hyperpolarized probes and labels for biosensors and the study of biomolecular processes.