Acyl derivatives of hyaluronan (acyl-HA) are promising materials for biomedical applications. Depending on the acyl length and the degree of substitution, these derivatives range from self-assembling water-soluble polymers to materials insoluble in aqueous environments. The behaviour of acyl-HA was studied in solution, but little attention was paid to the solid state, despite its importance for applications such as medical device fabrication. We thus used X-ray scattering and electron microscopy to explore the solid-state nano-structure of acyl-HA. The set of samples included various substituents, substitution degrees and molecular weights. The obtained data showed that all studied acyl-HA materials contained structures with dimensions on the order of nanometres that were not present in unmodified HA. The size of the nanostructures increased with the acyl length, while the degree of substitution and molecular weight had negligible effects. We suggest that the observed nanostructure corresponds to a distribution of hydrophobic domains in a hydrophilic matrix of unmodified HA segments.

• Klíčová slova
• Electron microscopy, Hyaluronan, Hydrophobization, Nanostructure, Small-angle X-ray scattering, Solid-state,
• Publikační typ
• časopisecké články MeSH

Changes in the protonation state of lyophilized proteins can impact structural integrity, chemical stability, and propensity to aggregate upon reconstitution. When a buffer is chosen, the freezing/drying process may result in dramatic changes in the protonation state of the protein due to ionization shift of the buffer. In order to determine whether protonation shifts are occurring, ionizable probes can be added to the formulation. Optical probes (dyes) have shown dramatic ionization changes in lyophilized products, but it is unclear whether the pH indicator is uniform throughout the matrix and whether the change in the pH indicator actually mirrors drug ionization changes. In solid-state NMR (SSNMR) spectroscopy, the chemical shift of the carbonyl carbon in carboxylic acids is very sensitive to the ionization state of the acid. Therefore, SSNMR can be used to measure ionization changes in a lyophilized matrix by employing a small quantity of an isotopically-labeled carboxylic acid species in the formulation. This paper compares the apparent pH of six trehalose-containing lyophilized buffer systems using SSNMR and UV-Vis diffuse reflectance spectroscopy (UVDRS). Both SSNMR and UVDRS results using two different ionization probes (butyric acid and bromocresol purple, respectively) showed little change in apparent acidity compared to the pre-lyophilized solution in a sodium citrate buffer, but a greater change was observed in potassium phosphate, sodium phosphate, and histidine buffers. While the trends between the two methods were similar, there were differences in the numerical values of equivalent pH (pHeq) observed between the two methods. The potential causes contributing to the differences are discussed.

• Klíčová slova
• Diffuse reflectance spectroscopy, Lyophilization, Solid-state NMR spectroscopy, Solid-state acidity, UV/VIS,
• MeSH
• fosfáty * chemie   MeSH
• histidin * chemie   MeSH
• koncentrace vodíkových iontů MeSH
• kyselina citronová chemie   MeSH
• lyofilizace * metody   MeSH
• magnetická rezonanční spektroskopie * metody   MeSH
• pufry MeSH
• spektrofotometrie ultrafialová metody   MeSH
• trehalosa * chemie   MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• fosfáty * MeSH
• histidin * MeSH
• kyselina citronová MeSH
• pufry MeSH
• trehalosa * MeSH

Recent work has identified a bis-(p-nitrophenyl)ureidodecalin anion carrier as a promising candidate for biomedical applications, showing good activity for chloride transport in cells yet almost no cytotoxicity. To underpin further development of this and related compounds, a detailed structural and binding investigation is reported. Crystal structures of the transporter as five solvates confirm the diaxial positioning of urea groups while revealing a degree of conformational flexibility. Structures of complexes with Cl- , Br- , NO3- , SO42- and AcO- , supported by computational studies, show how the binding site can adapt to accommodate these anions. 1 H NMR binding studies revealed exceptionally high affinities for anions in DMSO, decreasing in the order SO42- >H2 PO4- ≈HCO3- ≈AcO- ≫HSO4- >Cl- >Br- >NO3- >I- . Analysis of the binding results suggests that selectivity is determined mainly by the H-bond acceptor strength of different anions, but is also modulated by receptor geometry.

• Klíčová slova
• anions, host-guest interactions, hydrogen bonds, receptors, solid-state structures,
• MeSH
• anionty chemie   MeSH
• chloridy chemie   MeSH
• krystalografie rentgenová MeSH
• magnetická rezonanční spektroskopie MeSH
• močovina chemie   MeSH
• molekulární konformace MeSH
• molekulární počítače MeSH
• nitrofenoly chemie   MeSH
• vazebná místa MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• anionty MeSH
• bis-(p-nitrophenyl)ureidodecalin MeSH Prohlížeč
• chloridy MeSH
• močovina MeSH
• nitrofenoly MeSH

Reliable values of the solid-state NMR (SSNMR) parameters together with precise structural data specific for a given amino acid site in an oligopeptide are needed for the proper interpretation of measurements aiming at an understanding of oligopeptides' function. The periodic density functional theory (DFT)-based computations of geometries and SSNMR chemical shielding tensors (CSTs) of solids are shown to be accurate enough to support the SSNMR investigations of suitably chosen models of oriented samples of oligopeptides. This finding is based on a thorough comparison between the DFT and experimental data for a set of tripeptides with both 13Cα and 15Namid CSTs available from the single-crystal SSNMR measurements and covering the three most common secondary structural elements of polypeptides. Thus, the ground is laid for a quantitative description of local spectral parameters of crystalline oligopeptides, as demonstrated for the backbone 15Namid nuclei of samarosporin I, which is a pentadecapeptide (composed of five classical and ten nonproteinogenic amino acids) featuring a strong antimicrobial activity.

• Klíčová slova
• GIPAW, oligopeptides, plane-wave DFT, samarosporin, solid-state NMR,
• MeSH
• aminokyseliny chemie   MeSH
• izotopové značení MeSH
• magnetická rezonanční spektroskopie * metody   MeSH
• oligopeptidy chemie   izolace a purifikace   MeSH
• peptidy chemie   MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• aminokyseliny MeSH
• oligopeptidy MeSH
• peptidy MeSH

Vibrational circular dichroism (VCD) spectroscopy appears as a useful method for characterizing optically active substances in the solid state. This is particularly important for active pharmaceutical ingredients. However, measurement and interpretation of the spectra bring about many difficulties. To assess the experimental and computational methodologies, we explore an anti-inflammatory drug, naproxen. Infrared (IR) and VCD spectra of the pure compound and its cocrystals with alanine and proline were recorded, and the data were interpreted by quantum chemical simulations based on a cluster model and density functional theory. Although unpolarized IR spectroscopy can already distinguish pure ingredients from cocrystals or a mixture, the VCD technique is much more sensitive. For example, the naproxen carboxyl group strongly interacts with the zwitterionic alanine in the cocrystal via two strong hydrogen bonds, which results in a rather rigid structure crystallizing in the chiral P212121 Sohncke group and its VCD is relatively strong. In contrast, the d-proline and (S)-naproxen cocrystal (P21 group) involves a single hydrogen bond between the subunits, which together with a limited motion of the proline ring gives a weaker signal. Solid-state VCD spectroscopy thus appears useful for exploring composite crystal structures and interactions within them, including studies of pharmaceutical compounds.

• Klíčová slova
• alanine, cocrystals, density functional theory, naproxen, proline, solid state, spectra modeling, vibrational circular dichroism,
• MeSH
• alanin chemie   MeSH
• antiflogistika nesteroidní chemie   MeSH
• cirkulární dichroismus * metody   MeSH
• krystalizace MeSH
• molekulární modely MeSH
• naproxen * chemie   MeSH
• prolin chemie   MeSH
• spektrofotometrie infračervená MeSH
• stereoizomerie MeSH
• vibrace MeSH
• vodíková vazba MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• alanin MeSH
• antiflogistika nesteroidní MeSH
• naproxen * MeSH
• prolin MeSH

X-ray diffraction is a commonly used technique in the pharmaceutical industry for the determination of the atomic and molecular structure of crystals. However, it is costly, sometimes time-consuming, and it requires a considerable degree of expertise. Vibrational circular dichroism (VCD) spectroscopy resolves these limitations, while also exhibiting substantial sensitivity to subtle modifications in the conformation and molecular packaging in the solid state. This study showcases VCD's ability to differentiate between various crystal structures of the same molecule (polymorphs, cocrystals). We examined the most effective approach for producing high-quality spectra and unveiled the intricate link between structure and spectrum via quantum-chemical computations. We rigorously assessed, using alanine as a model compound, multiple experimental conditions on the resulting VCD spectra, with the aim of proposing an optimal and efficient procedure. The proposed approach, which yields reliable, reproducible, and artifact-free results with maximal signal-to-noise ratio, was then validated using a set comprising of three amino acids (serine, alanine, tyrosine), one hydroxy acid (tartaric acid), and a monosaccharide (ribose) to mimic active pharmaceutical components. Finally, the optimized approach was applied to distinguish three polymorphs of the antiviral drug sofosbuvir and its cocrystal with piperazine. Our results indicate that solid-state VCD is a prompt, cost-effective, and easy-to-use technique to identify crystal structures, demonstrating potential for application in pharmaceuticals. We also adapted the cluster and transfer approach to calculate the spectral properties of molecules in a periodic crystal environment. Our findings demonstrate that this approach reliably produces solid-state VCD spectra of model compounds. Although for large molecules with many atoms per unit cell, such as sofosbuvir, this approach has to be simplified and provides only a qualitative match, spectral calculations, and energy analysis helped us to decipher the observed differences in the experimental spectra of sofosbuvir.

• Klíčová slova
• Amino acids, Hydroxy acids, Polymorphs, Sofosbuvir, Solid-state, Vibrational circular dichroism,
• MeSH
• antivirové látky chemie   MeSH
• cirkulární dichroismus * MeSH
• krystalizace * MeSH
• molekulární modely MeSH
• sofosbuvir * chemie   MeSH
• vibrace MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• antivirové látky MeSH
• sofosbuvir * MeSH

Solid dispersions of active pharmaceutical ingredients are of increasing interest due to their versatile use. In the present study polyvinylpyrrolidone (PVP), poly[N-(2-hydroxypropyl)-metacrylamide] (pHPMA), poly(2-ethyl-2-oxazoline) (PEOx), and polyethylene glycol (PEG), each in three Mw, 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 (1)H-(13)C and (1)H-(1)H correlation experiments combined with T1((1)H) and T1ρ((1)H) 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 (13)C and (15)N CP/MAS NMR spectra combined with the measurements of (1)H-(15)N dipolar profiles. Overall potentialities and limitations of individual experimental techniques were thoroughly evaluated.

• MeSH
• Aspirin chemie   MeSH
• diferenciální skenovací kalorimetrie MeSH
• magnetická rezonanční spektroskopie * MeSH
• molekulární struktura MeSH
• suspenze chemie   MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• Aspirin MeSH
• suspenze MeSH

New drug formulations are sought for poorly water-soluble substances because there is a risk of compromised bioavailability if such substances are administered orally. Such active pharmaceutical ingredients can be reformulated as solid dispersions with suitable water-soluble polymers. In this contribution, formulation of a novel and physically stable dispersion of Simvastatin in poly(2-hydroxypropyl) methacrylamide (pHPMA) is demonstrated. Due to the limited water sorption of pHPMA and a high Tg, the prepared dispersion is more suited for oral administration and storage compared with neat amorphous Simvastatin. Surprisingly, the rate of global reorientation and the internal motion of Simvastatin molecules were enhanced and exhibited dynamical heterogeneities when incorporated into the pHPMA matrix. As revealed by solid-state nuclear magnetic resonance combined with Raman spectroscopy exploiting the fluorescence phenomenon the mobility of the ester and lactone components increased considerably, whereas the naphthalene ring remained rigid. Furthermore, the solid dispersion was found to be nano-heterogeneous with nanometer-sized Simvastatin domains. The presence of these clusters had no impact on the dynamics of the rigid pHPMA chains. Thus, the diffusion of Simvastatin molecules through the glassy pHPMA walls and the subsequent transformation of the clusters into larger crystallites were prevented. No crystallization was detected for more than two years.

• Klíčová slova
• Fluorescence, Pharmaceuticals, Raman spectroscopy, Simvastatin, Solid dispersions, Solid-state NMR,
• MeSH
• adsorpce MeSH
• diferenciální skenovací kalorimetrie MeSH
• kyseliny polymethakrylové chemie   MeSH
• magnetická rezonanční spektroskopie MeSH
• molekulární struktura MeSH
• Ramanova spektroskopie MeSH
• simvastatin chemie   MeSH
• stabilita léku MeSH
• voda chemie   MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• Duxon MeSH Prohlížeč
• kyseliny polymethakrylové MeSH
• simvastatin MeSH
• voda MeSH

Recently, 2D nanomaterials such as transition metal carbides or nitrides (MXenes) and transition metal dichalcogenides (TMDs) have attracted ample attention in the field of energy storage devices specifically in supercapacitors (SCs) because of their high metallic conductivity, wide interlayer spacing, large surface area, and 2D layered structures. However, the low potential window (ΔV ≈ 0.6 V) of MXene e.g., Ti3 C2 Tx limits the energy density of the SCs. Herein, asymmetric supercapacitors (ASCs) are fabricated by assembling the exfoliated Ti3 C2 Tx (Ex-Ti3 C2 Tx ) as the negative electrode and transition metal chalcogenide (MoS3- x ) coated 3D-printed nanocarbon framework (MoS3- x @3DnCF) as the positive electrode utilizing polyvinyl alcohol (PVA)/H2 SO4 gel electrolyte, which provides a wide ΔV of 1.6 V. The Ex-Ti3 C2 Tx possesses wrinkled sheets which prevent the restacking of Ti3 C2 Tx 2D layers. The MoS3- x @3DnCF holds a porous structure and offers diffusion-controlled intercalated pseudocapacitance that enhances the overall capacitance. The 3D printing allows a facile fabrication of customized shaped MoS3- x @3DnCF electrodes. Employing the advantages of the 3D-printing facilities, two different ASCs, such as sandwich- and interdigitated-configurations are fabricated. The customized ASCs provide excellent capacitive performance. Such ASCs combining the MXene and electroactive 3D-printed nanocarbon framework can be used as potential energy storage devices in modern electronics.

• Klíčová slova
• 3D printing, MXene, MoS 2, TMDs, Ti 3C 2, asymmetric supercapacitors, solid-state,
• Publikační typ
• časopisecké články MeSH

Exciting developments in new experimental methods for multidimensional solid-state NMR spectroscopy have recently been achieved using optimal-control theory. These results, in turn, have triggered the development of new pulse sequences based on traditional analytical theories. This trend article summarises the key steps leading to these advancements. It also describes additional applications of optimal control beyond structural biology and envisions similar progress in the NMR of solid materials. Despite attractive features of optimal-control pulse sequences demonstrated in the proof-of-concept studies, their experimental utilization remains sparse, probably due to the lack of awareness among experimentalists. We hope this mini-review helps to spread optimal-control methods into routine experimental workflows. Furthermore, we offer a personal outlook on how numerical optimisations could in general enhance the experimental capabilities of solid-state NMR in the near future, with optimal control serving as a pioneer exploring new possibilities.

• Publikační typ
• časopisecké články MeSH
• přehledy MeSH