Shortest path based decision making using probabilistic inference

Despite the extensive use of boron-modified phenol–formaldehyde polymers as insulating materials in soft magnetic composites (SMCs), the structure and arrangement of the inorganic cross-linking units in these systems have not been fully elucidated. To clarify the structure, configuration, and distribution of the boron cross-links in these materials, phenol–formaldehyde resins modified by boric acid were synthesized and characterized using advanced multiple-quantum ¹¹B–¹¹B MAS NMR correlation techniques combined with the quantum chemical geometry optimizations and the subsequent ¹¹B NMR chemical shielding calculations. The analyses of the resulting spectra revealed a well-evolved (high-density) phenol–formaldehyde polymer network additionally strengthened by nitrogen and boron cross-links. The boron-based cross-links were attributed to monoester (ca. 10%) and diester (ca. 90%) complexes (six-membered spirocyclic borate anions) with strictly tetrahedral coordination (B^IV). During the thermal treatment, the monoester and diester borate complexes underwent additional transformation in which the spirocyclic borate anions were more tightly incorporated into the polymer matrix via additional <i>N</i>-type (amino) cross-links. A ¹¹B–¹¹B double-quantum correlation MAS NMR experiment revealed that the majority of the monoester and diester borate complexes (ca. 80%) were uniformly distributed within and effectively isolated by the polymer matrix, with an average ¹¹B···¹¹B interatomic distance greater than 6 Å. A non-negligible part of the spirocyclic borate anion complexes (ca. 20%), however, existed in pairs or small clusters in which the average ¹¹B···¹¹B interatomic distance was less than 5.5 Å. In addition, the formation of homodimers (diester–diester) was demonstrated to be preferred over the formation of heteroclusters (monoester–diester)

Efficient Strategy for Determining the Atomic-Resolution Structure of Micro- and Nanocrystalline Solids within Polymeric Microbeads: Domain-Edited NMR Crystallography

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 <i>T</i>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

Structural Diversity of Solid Dispersions of Acetylsalicylic Acid As Seen by Solid-State NMR

Solid dispersions of active pharmaceutical ingredients are of increasing interest due to their versatile use. In the present study polyvinylpyrrolidone (PVP), poly­[<i>N</i>-(2-hydroxypropyl)-metacrylamide] (pHPMA), poly­(2-ethyl-2-oxazoline) (PEOx), and polyethylene glycol (PEG), each in three <i>M</i>_w, were used to demonstrate structural diversity of solid dispersions. Acetylsalicylic acid (ASA) was used as a model drug. Four distinct types of the solid dispersions of ASA were created using a freeze-drying method: (i) crystalline solid dispersions containing nanocrystalline ASA in a crystalline PEG matrix; (ii) amorphous glass suspensions with large ASA crystallites embedded in amorphous pHPMA; (iii) solid solutions with molecularly dispersed ASA in rigid amorphous PVP; and (iv) nanoheterogeneous solid solutions/suspensions containing nanosized ASA clusters dispersed in a semiflexible matrix of PEOx. The obtained structural data confirmed that the type of solid dispersion can be primarily controlled by the chemical constitutions of the applied polymers, while the molecular weight of the polymers had no detectable impact. The molecular structure of the prepared dispersions was characterized using solid-state NMR, wide-angle X-ray scattering (WAXS), and differential scanning calorimetry (DSC). By applying various ¹H–¹³C and ¹H–¹H correlation experiments combined with <i>T</i>₁(¹H) and <i>T</i>_1ρ(¹H) relaxation data, the extent of the molecular mixing was determined over a wide range of distances, from intimate intermolecular contacts (0.1–0.5 nm) up to the phase-separated nanodomains reaching ca. 500 nm. Hydrogen-bond interactions between ASA and polymers were probed by the analysis of ¹³C and ¹⁵N CP/MAS NMR spectra combined with the measurements of ¹H–¹⁵N dipolar profiles. Overall potentialities and limitations of individual experimental techniques were thoroughly evaluated

Exploring the Molecular-Level Architecture of the Active Compounds in Liquisolid Drug Delivery Systems Based on Mesoporous Silica Particles: Old Tricks for New Challenges

A general, easy-to-implement strategy for mapping the structure of organic phases integrated in mesoporous silica drug delivery devices is presented. The approach based on a few straightforward solid-state NMR techniques has no limitations regarding concentrations of the active compounds and enables straightforward discrimination of various organic phases. This way, among a range of typical arrangements of the active compounds and solvent molecules, a unique, previously unknown organogel phase of the self-assembled tapentadol in glucofurol as a solvent was unveiled and clearly identified. Subsequently, with an aid of 2D ¹H–¹H MAS NMR and high-level quantum-chemical calculations this uncommon low-molecular-weight organogel phase, existing exclusively in the porous system of the silica carrier, was described in detail. The optimized model revealed the tendency of tapentadol molecules to form hydrophobic arrangements through −OH···π interactions combined with π–π stacking occurring in the core of API aggregates, thus precluding the formation of hydrogen bonds with the solvent. Overall, the proposed experimental approach allows for clear discrimination of a variety of local structures of active compounds loaded in mesoporous silica drug delivery devices in reasonably short time being applicable for advancement of novel drug delivery systems in pharmaceutical industry

Interface Induced Growth and Transformation of Polymer-Conjugated Proto-Crystalline Phases in Aluminosilicate Hybrids: A Multiple-Quantum ²³Na–²³Na MAS NMR Correlation Spectroscopy Study.

Nanostructured materials typically offer enhanced physicochemical properties because of their large interfacial area. In this contribution, we present a comprehensive structural characterization of aluminosilicate hybrids with polymer-conjugated nanosized zeolites specifically grown at the organic–inorganic interface. The inorganic amorphous Al–O–Si framework is formed by alkali-activated low-temperature transformation of metakaoline, whereas simultaneous copolymerization of organic comonomers creates a secondary epoxide network covalently bound to the aluminosilicate matrix. This secondary epoxide phase not only enhances the mechanical integrity of the resulting hybrids but also introduces additional binding sites accessible for compensating negative charge on the aluminosilicate framework. This way, the polymer network initiates growth and subsequent transformation of protocrystalline short-range ordered zeolite domains that are located at the organic–inorganic interface. By applying an experimental approach based on 2D ²³Na–²³Na double-quantum (DQ) MAS NMR spectroscopy, we discovered multiple sodium binding sites in these protocrystalline domains, in which immobilized Na⁺ ions form pairs or small clusters. It is further demonstrated that these sites, the local geometry of which allows for the pairing of sodium ions, are preferentially occupied by Pb²⁺ ions during the ion exchange. The proposed synthesis protocol thus allows for the preparation of a novel type of geopolymer hybrids with polymer-conjugated zeolite phases suitable for capturing and storage of metal cations. The demonstrated ²³Na–²³Na DQ MAS NMR combined with DFT calculations represents a suitable approach for understanding the role of Na⁺ ions in aluminositicate solids and related inorganic–organic hybrids, particularly their specific arrangement and clustering at interfacial areas

Interface Induced Growth and Transformation of Polymer-Conjugated Proto-Crystalline Phases in Aluminosilicate Hybrids: A Multiple-Quantum ²³Na–²³Na MAS NMR Correlation Spectroscopy Study.

Nanostructured materials typically offer enhanced physicochemical properties because of their large interfacial area. In this contribution, we present a comprehensive structural characterization of aluminosilicate hybrids with polymer-conjugated nanosized zeolites specifically grown at the organic–inorganic interface. The inorganic amorphous Al–O–Si framework is formed by alkali-activated low-temperature transformation of metakaoline, whereas simultaneous copolymerization of organic comonomers creates a secondary epoxide network covalently bound to the aluminosilicate matrix. This secondary epoxide phase not only enhances the mechanical integrity of the resulting hybrids but also introduces additional binding sites accessible for compensating negative charge on the aluminosilicate framework. This way, the polymer network initiates growth and subsequent transformation of protocrystalline short-range ordered zeolite domains that are located at the organic–inorganic interface. By applying an experimental approach based on 2D ²³Na–²³Na double-quantum (DQ) MAS NMR spectroscopy, we discovered multiple sodium binding sites in these protocrystalline domains, in which immobilized Na⁺ ions form pairs or small clusters. It is further demonstrated that these sites, the local geometry of which allows for the pairing of sodium ions, are preferentially occupied by Pb²⁺ ions during the ion exchange. The proposed synthesis protocol thus allows for the preparation of a novel type of geopolymer hybrids with polymer-conjugated zeolite phases suitable for capturing and storage of metal cations. The demonstrated ²³Na–²³Na DQ MAS NMR combined with DFT calculations represents a suitable approach for understanding the role of Na⁺ ions in aluminositicate solids and related inorganic–organic hybrids, particularly their specific arrangement and clustering at interfacial areas

Structure and Dynamics of Alginate Gels Cross-Linked by Polyvalent Ions Probed via Solid State NMR Spectroscopy

Alginate gels are an outstanding biomaterial widely applicable in tissue engineering, medicine, and pharmacy for cell transplantation, wound healing and efficient bioactive agent delivery, respectively. This contribution provides new and comprehensive insight into the atomic-resolution structure and dynamics of polyvalent ion-cross-linked alginate gels in microbead formulations. By applying various advanced solid-state NMR (ssNMR) spectroscopy techniques, we verified the homogeneous distribution of the cross-linking ions in the alginate gels and the high degree of ion exchange. We also established that the two-component character of the alginate gels arises from the concentration fluctuations of residual water molecules that are preferentially localized along polymer chains containing abundant mannuronic acid (M) residues. These hydrated M-rich blocks tend to self-aggregate into subnanometer domains. The resulting coexistence of two types of alginate chains differing in segmental dynamics was revealed by ¹H–¹³C dipolar profile analysis, which indicated that the average fluctuation angles of the stiff and mobile alginate segments were about 5–9° or 30°, respectively. Next, the ¹³C CP/MAS NMR spectra indicated that the alginate polymer microstructure was strongly dependent on the type of cross-linking ion. The polymer chain regularity was determined to systematically decrease as the cross-linking ion radius decreased. Consistent with the ¹H–¹H correlation spectra, regular structures were found for the gels cross-linked by relatively large alkaline earth cations (Ba²⁺, Sr²⁺, or Ca²⁺), whereas the alginate chains cross-linked by bivalent transition metal ions (Zn²⁺) and trivalent metal cations (Al³⁺) exhibited significant irregularities. Notably, however, the observed disordering of the alginate chains was exclusively attributed to the M residues, whereas the structurally well-defined gels all contained guluronic acid (G) residues. Therefore, a key role of the units in M-rich blocks as mediators promoting the self-assembly of alginate chains was experimentally confirmed. Finally, combining 2D ²⁷Al 3Q/MAS NMR spectroscopy with density functional theory (DFT) calculations provided previously unreported insight into the structure of the Al³⁺ cross-linking centers. Notably, even with a low residual amount of water, these cross-linking units adopt exclusively 6-fold octahedral coordination and exhibit significant motion, which considerably reduces quadrupolar coupling constants. Thus, the experimental strategy presented in this study provides a new perspective on cross-linked alginate structure and dynamics for which high-quality diffraction data at the atomic resolution level are inherently unavailable