Highly Efficient Polarizing Agents for MAS‐DNP of Proton‐Dense Molecular Solids #DNPNMR

Published: Monday, 21 March 2022 - 00:00 UTC

Author: Thorsten Maly

Harrabi, Rania, Thomas Halbritter, Fabien Aussenac, Ons Dakhlaoui, Johan Tol, Krishna K. Damodaran, Daniel Lee, et al. “Highly Efficient Polarizing Agents for MAS‐DNP of Proton‐Dense Molecular Solids.” Angewandte Chemie International Edition, February 2022.

https://doi.org/10.1002/anie.202114103.

Efficiently hyperpolarizing proton-dense molecular solids through dynamic nuclear polarization (DNP) solidstate NMR is still an unmet challenge. Polarizing agents (PAs) developed so far do not perform well on proton-rich systems, such as organic microcrystals and biomolecular assemblies. Herein we introduce a new PA, cAsymPol-POK, and report outstanding hyperpolarization efficiency on 12.76 kDa U-13C,15N-labeled LecA protein and pharmaceutical drugs at high magnetic fields (up to 18.8 T) and fast magic angle spinning (MAS) frequencies (up to 40 kHz). The performance of cAsymPol-POK is rationalized by MASDNP simulations combined with electron paramagnetic resonance (EPR), density functional theory (DFT) and molecular dynamics (MD). This work shows that this new biradical is compatible with challenging biomolecular applications and unlocks the rapid acquisition of 13C–13C and 15N–13C correlations of pharmaceutical drugs at natural isotopic abundance, which are key experiments for structure determination.