No abstract

Precise structural analysis of multiphase polymeric nanocomposites remains a challenge even in the presence of high-quality X-ray diffraction data. This contribution thus addresses our attempt to formulate a combined analytical strategy for obtaining the atomic-resolution structure of multicomponent polymeric solids with complex nanodomain architecture. In this strategy, through the application of T 1-filtered solid-state NMR spectroscopy, the individual components are successively distinguished and selected, and the corresponding 1H, 13C, and 15N isotropic chemical shifts are explicitly assigned. Thereafter, using an automated protocol allowing for processing and statistical analysis of large data sets, the experimentally determined NMR parameters are systematically compared with those DFT-calculated for the representative set of crystal structure predictions. Particular attention is devoted to the analysis of NMR parameters of hydrogen-bonded protons which are responsible for molecular packing. As a result of this search, the structures of micro- and nanosized crystallites dispersed in the polymeric matrix are determined and independently verified by the measurements of through-space dipolar couplings. The potential of this strategy is demonstrated on injectable polyanhydride microbeads consisting of a mixture of microcrystalline decitabine and nanocrystalline sebacic acid, both incorporated in the semicrystalline polymeric matrix of poly­(sebacic acid). Through the synergistic interplay between the measurements, calculations, and the statistical analysis, we have developed an integrated approach providing structural information that is challenging to elucidate using conventional diffraction approaches. This combination of experimental and theoretical approaches enables one to determine the structural arrangements of molecules in situations which are not tractable by conventional spectroscopic techniques.

Fluorine-19 magnetic resonance imaging (19F MRI) enables detailed in vivo tracking of fluorine-containing tracers and is therefore becoming a particularly useful tool in noninvasive medical imaging. In previous studies, we introduced biocompatible polymers based on the hydrophilic monomer N-(2-hydroxypropyl)­methacrylamide (HPMA) and the thermoresponsive monomer N-(2,2-difluoroethyl)­acrylamide (DFEA). These polymers have abundant magnetically equivalent fluorine atoms and advantageous properties as 19F MRI tracers. Furthermore, in this pilot study, we modified these polymers by introducing a redox-responsive monomer. As a result, our polymers changed their physicochemical properties once exposed to an oxidative environment. Reactive oxygen species (ROS)-responsive polymers were prepared by incorporating small amounts (0.9–4.5 mol %) of the N-[2-(ferrocenylcarboxamido)­ethyl]­acrylamide (FcCEA) monomer, which is hydrophobic and diamagnetic in the reduced electroneutral (Fe­(II), ferrocene) state but hydrophilic and paramagnetic in the oxidized (Fe­(III), ferrocenium cation) state. This property can be useful for theranostic purposes (therapy and diagnostic purposes), especially, in terms of ROS-responsive drug-delivery systems. In the reduced state, these nanoparticles remain self-assembled with the encapsulated drug but release the drug upon oxidation in ROS-rich tumors or inflamed tissues.