Publication
A new 3.2 mm 1H–19F–X magic angle spinning dynamic nuclear polarization NMR (MAS DNP-NMR) probe was developed with a unique coil design with separate radiofrequency channels for 1H excitation and 13C or 19F detection to enable acquisition of 1H–19F cross-polarization (CP) MAS experiments, direct-detected 19F spectra with proton decoupling, and acquisition on 13C with simultaneous double decoupling on the 1H and 19F channels as well as 1H–19F–13C double-CP experiments under low temperature MAS DNP conditions. We use these sequences to study AZD2811, which is an active pharmaceutical ingredient (API), in its pure dry state as well as in its corresponding drug delivery formulation consisting of drug-loaded polymeric nanoparticles (PNPs). Included in this study are also small interfering RNAs (siRNAs) for therapeutic targeting of peptidyl-prolyl cis–trans isomerase B (Ppib) mRNA. We demonstrate that 1H–19F CP MAS experiments performed on the new HFX probe represent a notable advantage over usually acquired direct-detected 19F experiments. The indirect 19F DNP enhancement εon/off(19F) = 26 was obtained via 1H–19F CP for the pure API impregnated with DNP solution, with an overall 30-fold sensitivity gain compared to the direct-detected 19F experiment under similar conditions. DNP enhancement value of εon/off(19F) = 42 was obtained via 1H–19F CP for the polymeric nanoparticle suspension and εon/off(19F) ≈ 150 were obtained for two different siRNAs in frozen DNP solution.