Highly Efficient Polarizing Agents for MAS-DNP of Proton-Dense Molecular Solids

Efficiently hyperpolarizing proton-dense molecular solids through dynamic nuclear polarization (DNP) solid-state 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-C-13,N-15-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 MAS-DNP 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 C-13-C-13 and N-15-C-13 correlations of pharmaceutical drugs at natural isotopic abundance, which are key experiments for structure determination.

Automated summary

Efficiently polarizing proton-dense molecular solids through dynamic nuclear polarization (DNP) solid-state NMR has been a great challenge. In this study, we introduce a new polarizing agent, cAsymPol-POK, which shows outstanding performance in polarizing biomolecular assemblies and organic microcrystals at high magnetic fields and fast magic angle spinning frequencies. Simulation and experimental results demonstrate the compatibility of cAsymPol-POK with challenging biomolecular applications and its ability to rapidly acquire crucial structural data of pharmaceutical drugs at natural isotopic abundance.