Recent progress in high-field liquid-state Overhauser dynamic nuclear polarization

Overhauser-effect dynamic nuclear polarization (OE-DNP) is an emerging method for enhancing the sensitivity of high-resolution nuclear magnetic resonance (NMR) in liquids. OE-DNP generates nuclear spin hyperpolarization by electron-to-nuclear cross-relaxation between the analyte and a paramagnetic polarizing agent doped into the NMR solution. The key advantage of this method is the in situ enhancement of nuclear polarization under steady-state, which is inherently compatible with multiscan signal averaging and multidimensional NMR. Although OE-DNP has been known for several decades, recent demonstrations of one and two-dimensional OE-DNP at high magnetic fields (9 and 14 Tesla) have expanded its application, and opened up new possibilities for NMR-based analysis of drugs, natural products, and heterogeneous catalytic processes. In parallel, progress in quantum chemical calculations and numerical simulation capabilities have started to unravel the atomistic details of the OE-DNP mechanism at high magnetic fields. These studies revealed that hyperpolarization generation relies on sub-picosecond molecular dynamics and hyperfine coupling through non-covalent intermolecular interactions, such as hydrogen and halogen bonds. This understanding enables not only the rational design of OE-DNP experiments tailored to different samples, but provides new insight into fundamental physics and chemistry in solution as well. In this review, we summarize recent developments of OE-DNP and outline guidelines for its implementation to different nuclei. We start with an overview of the current theoretical framework of OE-DNP, and subsequently, discuss the role of electronic spin saturation and its implications for microwave hardware design at 9 and 14 Tesla. Finally, we review high-field OE-DNP performance of the most extensively investigated nuclei, ¹³C, ¹H, ¹⁹F and ³¹P, and representative applications that illustrate the future potential of this method.