Search Results (154)

Background/Objectives: Ursodeoxycholic acid (UDCA) is a bile acid widely used for the treatment of cholestatic liver diseases; however, its poor aqueous solubility represents a major limitation for the development of oral liquid formulations, particularly in pediatric patients requiring accurate and flexible dosing. This study aimed to develop and characterize a fully solubilized extemporaneous UDCA oral formulation using the ready-to-use vehicle Wagner, with particular emphasis on the role of hydroxypropyl-β-cyclodextrin (HP-β-CD) as a solubilizing excipient. Methods: Phase-solubility studies, Job’s plot analysis, and ¹H NMR spectroscopy were performed to investigate the host–guest interaction between UDCA and HP-β-CD, confirming the formation of a stable 1:1 inclusion complex responsible for a marked increase in drug solubility. The aqueous solubility of UDCA increased from approximately 0.02 mg/mL in water to 31 ± 1 mg/mL in the Wagner base containing HP-β-CD, compared to ~10 mg/mL in the corresponding cyclodextrin-free vehicle. Chemical stability was evaluated using an HPLC method adapted from the European Pharmacopoeia, employing dual detection (refractive index and photodiode array detector) to ensure specificity and stability-indicating capability. Results: The UDCA solution (20 mg/mL) remained chemically stable for at least 4 months under refrigerated (4–8 °C) and room temperature (25 °C) conditions, with only moderate degradation observed at 40 °C. Physical stability studies confirmed the absence of precipitation, phase separation, or significant pH variations under all storage conditions. Conclusions: Wagner-based formulation enabled the development of a stable and homogeneous UDCA oral solution, providing a complementary formulation strategy to conventional suspension-based preparations. This approach represents a robust and patient-oriented strategy for extemporaneous compounding, particularly suitable for pediatric use. Full article

To address the common drawbacks of polyamine-based CO₂ absorbents, such as high viscosity and precipitation at high CO₂ loading, a novel liquid–liquid biphasic absorbent composed of triethylenetetramine (TETA), 1-(2-aminoethyl)piperazine (AEP), N,N-dimethylacetamide (DMAC), and H₂O was developed in this study. By comprehensively evaluating CO₂ saturation loading, phase separation behavior, rheological properties of the CO₂-rich phase, precipitation suppression, and desorption–regeneration performance, the optimal absorbent formulation was identified as 20 wt% TETA + 10 wt% AEP + 40 wt% DMAC + 30 wt% H₂O. The optimized system enabled more than 98% of the CO₂ absorption products to be concentrated in the lower phase, which accounted for only 56% of the total liquid volume. Compared with the AEP-free TETA/DMAC/H₂O system, the optimized AEP-modified absorbent effectively eliminated precipitation and reduced the viscosity of the CO₂-rich phase to 62.3 mPa·s, while also improving the desorption behavior and cyclic stability of the system. In addition, ¹³C NMR analysis suggested that the salting-out effect is the main driving force for phase separation, with ionic products preferentially enriched in the aqueous phase to form the CO₂-rich lower phase. AEP contributes to viscosity reduction, precipitation suppression, and enhanced regeneration by weakening carbamate aggregation through steric hindrance and promoting bicarbonate formation. Full article

Silica dispersion in rubber matrices remains a critical issue due to the polarity mismatch between silica and the rubber phase. This study aimed to synthesize functionalized liquid polyisoprene rubber (F-LIR) and evaluate its role in improving the interfacial interaction between silica and solution styrene–butadiene rubber (SSBR). F-LIR was synthesized by introducing an alkoxysilane-containing functionalizing agent at the termination stage of anionic polymerization. Fourier transform infrared spectroscopy (FT-IR) and proton nuclear magnetic resonance spectroscopy (¹H-NMR) were used to confirm the successful introduction of silyl groups at the chain ends of liquid polyisoprene. The optimal loading of F-LIR in SSBR was evaluated through bound rubber content, dynamic mechanical analysis, and mechanical performance testing. The results demonstrated that F-LIR improved the tensile strength, modulus at 300% elongation, and bound rubber content of SSBR composites. These enhancements are attributed to the reaction between the silyl groups of F-LIR and surface hydroxyl groups of silica, together with the co-crosslinking interaction between F-LIR and SSBR. The composites containing 4 phr F-LIR exhibited the best overall balance of properties. This study provides a novel method for synthesizing F-LIR, which bridges silica and the rubber matrix by enhanced filler–rubber interactions at the filler–rubber interface. Full article

This study resolves the apparent breakdown of the Korringa relation in disordered liquid metals by investigating Ga-based alloys (EGaIn and Galinstan). By integrating temperature-dependent Knight shifts (K) with longitudinal (T₁) and transverse (T₂) relaxation measurements, we demonstrate that deviations from classical behavior arise from neglecting transverse spin dephasing induced by structural and electronic disorder. While solid-state alloys follow the conventional Korringa law, the liquid phase exhibits significant discrepancies between T₁ and T₂ due to enhanced electron scattering and fluctuating hyperfine fields. By explicitly incorporating T₂ into a modified framework, the proportionality between the Knight shift and nuclear relaxation is quantitatively restored. This establishes transverse relaxation as a critical parameter for describing nuclear spin dynamics in complex liquid metals, reinforcing NMR as a powerful local probe for optimizing next-generation liquid metal technologies. Full article

Phaeodactylum tricornutum was cultivated in a 1000 L photobioreactors using f/2 medium. The resulting algal biomass contained 24.5% lipids, 37.8% protein, 19.4% carbohydrates, and had a gross energy content of 19.8 MJ/kg. These components were sequentially extracted. The ultra-high performance liquid chromatography-high resolution mass spectrometry (UHPLC-HRMS) analysis of lipids revealed 35 triacylglycerols, a wide range of galactolipids and phospholipids including a novel sulfoquinovosyl diacylglycerol (SQDG), namely SQDG(C16:1/C24:0), characterized by mass fragmentation analysis. Additionally, three sulfoquinovosyl monoacylglycerols (SQMGs) with C14:0, C16:0, and C16:1 fatty acyl chain were detected in P. tricornutum for the first time. Fatty acid analysis further confirmed that P. tricornutum is an excellent source of ecosapentaenoic acid, which is predominantly present in triacylglycerol and glycolipid forms. CombiFlash chromatography allowed for the separation of monogalactosyldiacylglycerols, digalactosyldicylglycerols, SQDGs and phosphatidycholines, and their structure were confirmed by NMR spectral analysis. Fucoxanthin was the major carotenoid, and the study showed all essential amino acids required for humans and fish were present in it. A two-phase in vitro gastric/pancreatic digestibility assay showed high protein digestibility for both whole biomass (89%) and protein isolate (77%). Monosaccharide analysis showed that polysaccharides extracted by EtOH precipitation after alkaline extraction and by hot water extraction contained similar monomers with different relative intensities. Protein isolates and polysaccharides exhibited antioxidant properties. Full article

Background/Objectives: Saponins have recently emerged as promising natural products that enhance toxin-based anticancer therapeutics by improving cytosol uptake. This study aimed to identify structurally defined novel natural saponins and evaluate their ability to enhance anticancer cytotoxicity. Methods: The roots of Saponaria officinalis L. were extracted with aqueous ethanol and purified by silica gel column chromatography and reverse-phase high-performance liquid chromatography (RP HPLC). The structures of new saponins were elucidated by NMR spectroscopy and mass spectrometry. Biological activity was assessed in vitro using multiple cancer cell lines. Results: Two pairs of structurally defined pure saponins were obtained: SO1406 and SO1448, and SO1684 and SO1726. Structural elucidation revealed that SO1684 and SO1726 share the core structure 3-O-β-D-Gal-(1→2)-[β-D-Xyl-(1→3)]-β-D-GlcA-gypsogenin-28-O-β-D-Qui-(1→4)-[β-D-Xyl-(1→3)-β-D-Xyl-(1→4)]-α-L-Rha-(1→2)-β-D-Fuc, with SO1684 acetylated at Qui O-4 and SO1726 bearing additional acetylation at Qui O-3. Deacetylation of either SO1684 or SO1726 afforded a known saponin SA1641 isolated from Saponinum album (Merck). Similarly, SO1406 and SO1448 were identified as 3-O-β-D-Gal-(1→2)-[β-D-Xyl-(1→3)]-β-D-GlcA-gypsogenin-28-O-β-D-Xyl-(1→4)-α-L-Rha-(1→2)-β-D-Fuc derivatives, each acetylated at Fuc O-4, with SO1448 containing an additional acetyl group at Fuc O-3. Among the isolated compounds, SO1684 is a known saponin and SO1406 exhibited the most pronounced biological activity, significantly enhancing the cytotoxicity of the ribosome-inactivating protein saporin (SAP) in the MDA-MB231 (triple-negative breast cancer) cell line. Conclusions: SO1406 demonstrates strong cytotoxicity-enhancing activity, highlighting the significant potential of structurally defined natural saponins to advance intracellular delivery and improve the therapeutic performance of protein-based anticancer agents. Full article

The separation of rare earth elements (REEs) with similar chemical properties remains a relevant challenge today, most often addressed using liquid–liquid and solid-phase extraction with various chelating agents. Excellent complexing agents for REEs are 1,3-diketones and their analogs. We have for the first time proposed a method for preparing a material consisting of a covalently immobilized 3-acyl-4-hydroxycoumarin ligand on silica. For its synthesis, we employed a strategy based on the “click” reaction of 3-azidopropyl silica with a propargyl-containing coumarin–chalcone conjugate—this approach is the most tolerant and does not affect the coordinationally active fragment of the ligand. The material was characterized by thermal analysis, IR spectroscopy, and ¹³C NMR. The potential of the synthesized material for REE preconcentration was demonstrated at pH 5–5.5: high extraction efficiency for Gd(III), Dy(III), Er(III), Eu(III), Sm(III), and Yb(III) was observed, with fast adsorption kinetics (30 min) and extraction degrees of ~98%. Under unified conditions of static and dynamic extraction for Gd(III), Dy(III), Er(III), Eu(III), Sm(III), and Yb(III), affinity series toward the surface were obtained as a function of the distribution coefficient. It was shown that 10-fold molar excesses of Fe(III), Al(III), Cu(II), Ni(II), and Co(II) allow retention of more than 95% extraction for Dy(III) and Er(III). After adsorption of Dy(III) and Er(III), shifts in the carbonyl group absorption bands are visible in the IR spectra of the material, indicating a chelating mechanism of sorption. Additional studies are required for implementation in analytical and preparative REE separation schemes; however, preliminary data show that the material is a highly active adsorbent. Full article

Cholesterol plays a fundamental role in the human body—it stabilizes cell membranes, modulates gene expression, and is a precursor to steroid hormones, vitamin D, and bile salts. Its correct level is crucial for homeostasis, while both excess and deficiency are associated with serious metabolic and health consequences. Excessive accumulation of cholesterol leads to the development of atherosclerosis, while its deficiency disrupts the transport of fat-soluble vitamins. Magnetic resonance spectroscopy (MRS) enables the detection of cholesterol esters and the differentiation between their liquid and crystalline phases, but the technical limitations of clinical MRI systems require the use of dedicated coils and sequence modifications. This study demonstrates the feasibility of using MRS to identify cholesterol-specific spectral signatures in atherosclerotic plaque through ex vivo analysis. Using a custom-designed experimental coil adapted for small-volume samples, we successfully detected characteristic cholesterol peaks from plaque material dissolved in chloroform, with spectral signatures corresponding to established NMR databases. To further enhance spectral quality, a deep-learning denoising framework based on a 1D U-Net architecture was implemented, enabling the recovery of low-intensity cholesterol peaks that would otherwise be obscured by noise. The trained U-Net was applied to experimental MRS data from atherosclerotic plaques, where it significantly outperformed traditional denoising methods (Gaussian, Savitzky–Golay, wavelet, median) across six quantitative metrics (SNR, PSNR, SSIM, RMSE, MAE, correlation), enhancing low-amplitude cholesteryl ester detection. This approach substantially improved signal clarity and the interpretability of cholesterol-related resonances, supporting more accurate downstream spectral assessment. The integration of MRS with NMR-based lipidomic analysis, which allows the identification of lipid signatures associated with plaque progression and destabilization, is becoming increasingly important. At the same time, the development of high-resolution techniques such as μOCT provides evidence for the presence of cholesterol crystals and their potential involvement in the destabilization of atherosclerotic lesions. In summary, nanotechnology-assisted MRI has the potential to become an advanced tool in the proof-of-concept of atherosclerosis, enabling not only the identification of cholesterol and its derivatives, but also the monitoring of treatment efficacy. However, further clinical studies are necessary to confirm the practical usefulness of these solutions and their prognostic value in assessing cardiovascular risk. Full article

Siraitia grosvenorii (Swingle) C. Jeffrey is widely recognized for its anti-inflammatory properties, as well as its roles in lung purification, phlegm elimination, intestinal function regulation, and anti-tumor activity. Its pharmacological activity is attributed to a diversity of functional components. However, due to the extensive application of sweet glycosides in food additives, there have been few studies on non-sweet glycosides, particularly those with high polarity. This paper investigates the chemical constituents in the non-sweet glycosides fraction of S. grosvenorii juice. First, an MCI GEL CHP20P chromatographic column was utilized to enrich the non-sweet glycosides fraction. Furthermore, two-step medium-pressure liquid chromatography (MPLC) was performed for the efficient preparative separation of high-polarity non-sweet glycosides with similar structures, using C18 and silica gel as stationary phases, respectively. Seven non-sweet glycoside compounds were identified through NMR and mass spectrometry analyses, including three new compounds (4-hydroxyphenylethanol 4-O-β-D-glucopyranosyl-(1→6)-β-D-glucopyranoside, 4-hydroxyphenylethanol 4-O-β-D-glucopyranosyl-(1→2)-β-D-glucopyranosyl-(1→6)-β-D-glucopyranoside and n-butanol 1-O-β-D-glucopyranosyl-(1→2)-β-D-glucopyranosyl-(1→6)-β-D-glucopyranoside), as well as four known ones (α-D-glucopyranosyl-(1→4)-D-glucose, α-D-glucopyranosyl-(1→2)-β-D-fructofuranoside, methoxy hydroquinone diglucoside, and β-D-glucopyranoside). The results demonstrate that mixed-mode MPLC using different stationary phases is an efficient approach for separating non-sweet glycosides from S. grosvenorii. Full article

Four new porous homochiral metal–organic frameworks (MOFs), [M₂(camph)₂(bpa)]∙Solv (M = Co(II), Ni(II), Cu(II) and Zn(II)), based on (+)-camphoric acid (H₂camph) and 1,2-bis(4-pyridyl)ethane (bpa) were synthesized and characterized. The crystal structures of [Ni₂(camph)₂(bpa)] and [Zn₂(camph)₂(bpa)] were established by single-crystal X-ray diffraction analysis. Powder X-ray data prove the phase purity and isostructural nature of all four compounds. The thermal stability of [M₂(camph)₂(bpa)] was found to depend on the electronic configuration, as well as on the redox properties of the metal cation, and varied from 225 °C (M = Zn²⁺) to 375 °C (M = Ni²⁺). The reversible, solvent-induced sponge-like dynamics of the coordination frameworks was thoroughly investigated. Changes in the positions of reflexes, related to the length of the flexible bpa linker, were observed by powder XRD, pointing to transitions between an open-framework phase and a squeezed, non-porous phase in a crystal-to-crystal manner, while the integrity and connectivity of the coordination network were maintained. Size-selective adsorption from a benzene–cyclohexane 1:1 mixture on [Zn₂(camph)₂(bpa)] was studied by ¹H NMR analysis. The benzene-favorable composition of guest molecules (C₆H₆:C₆H₁₂ = 5:1) occluded within the host crystalline sponge revealed a preferable adsorption affinity towards smaller benzene compared with larger cyclohexane. High framework stability in various solvents, as well as successful molecular separation in the liquid state, validates the potential utilization of chiral porous metal(II) camphorate MOFs in important stereoselective applications. Full article

Background/Objectives: Coleus aromaticus (Lamiaceae), also known as Cuban oregano or Indian borage, is a semi-succulent perennial species widely used in traditional medicine for its therapeutic and nutritional properties. While its essential oils and aromatic fraction have been extensively investigated, the characterization of its non-volatile metabolites remains limited. The aim of this study was to explore the chemical composition of fresh leaves with a focus on the non-volatile fraction. Methods: Fresh leaves of C. aromaticus were cryogenically treated with liquid nitrogen, ground, and subjected to three different extraction procedures: hydroalcoholic maceration, ethyl acetate maceration, and liquid–liquid partitioning to obtain a dichloromethane organic phase and a hydroalcoholic phase. Extracts and fractions were analyzed by HPTLC and HPLC for metabolic profiling. In addition, the Bligh–Dyer method was applied to separate polar and non-polar metabolites, which were subsequently characterized using NMR spectroscopy. Results: Chromatographic analyses highlighted the occurrence and distribution of organic acids, polyphenols (notably flavonoids), and proteinogenic amino acids. Spectroscopic data confirmed the presence of diverse polar and non-polar metabolites, providing a more detailed chemical fingerprint of C. aromaticus. This integrated approach broadened the phytochemical profile of the species beyond the well-documented essential oils. Conclusions: The results contribute to a better understanding of the non-volatile metabolites of C. aromaticus, offering novel insights into its chemical diversity. These findings highlight the potential of this plant as a valuable source of bioactive compounds, supporting its future application in nutraceutical and pharmaceutical research. Full article

A robust and stability-indicating Reverse Phase-High Performance Liquid Chromatography (RP-HPLC) method was developed and validated for the quantitative determination of bexagliflozin and its related impurities in accordance with the International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH Q2(R1)) guidelines. Chromatographic separation was achieved on a C18 column using a mobile phase of methanol and ammonium acetate buffer (pH 4.2) in a 60:40 (v/v) ratio, with a flow rate of 1.0 mL·min⁻¹ and UV detection at 220 nm. The method was validated for linearity, sensitivity (LOD and LOQ), precision, robustness, and system suitability, all within acceptable limits for low-concentration analysis. Excellent linearity (r² > 0.999) and precision (%RSD 0.3–4.4%) confirmed its reliability for stability assessment. The assay was performed at 100 µg·mL⁻¹, where all validation parameters showed %RSD values ≤ 2%, demonstrating high precision and robustness. Forced degradation studies under acidic, basic, oxidative, photolytic, and thermal conditions revealed a major degradation product formed under acidic stress. This product was isolated and structurally characterized using LC–MS, ¹H NMR, and ¹³C NMR, and is reported here for the first time. The proposed RP-HPLC method proved to be specific, precise, and reliable for the determination of bexagliflozin and its related impurities, making it suitable for routine stability testing, quality control, and pharmaceutical development applications. Full article

The liquid crystal (LC) poly-γ-benzyl-L-glutamate (PBLG) is known to possess a narrow biphasic range at the phase transition from an isotropic liquid to an anisotropic liquid crystal. We have characterized the biphasic region via deuterium nuclear magnetic resonance (NMR) of the deuterated solvent CDCl₃, with which isotropic and anisotropic populations can unambiguously be identified and quantified due to the quadrupolar coupling induced by partial alignment. In addition to a dilution series, we measured the kinetics of the alignment inside the magnet for each dilution step and were able to follow the kinetic buildup of partial alignment. Beginning with the dynamic line broadening indicative of slow fluctuations, to microheterogeneous patches of isotropic and anisotropic islands, with increasing island size being consistent with sharpened spectra, ending in fully separated isotropic and anisotropic phases on top of each other after two weeks. In addition, we studied the influence of the two example guest molecules borneol and camphor—which essentially differ in their capability to act as hydrogen bond donors or acceptors—on the biphasic region of PBLG. Full article

Iron (Fe) chelators are used to treat iron-overloaded disorders, metal detoxification, radionuclides, and molecular imaging; however, they can cause side effects. In this study, we identified and characterized Coprogen B (CPGB), a hexadentate trihydroxamate siderophore secreted by the opportunistic dimorphic fungus Talaromyces marneffei and compared its properties with deferoxamine (DFO). Siderophore production was enriched from a ΔsreA strain and purified via Amberlite XAD2 and Sephadex LH20 chromatography, followed by reverse-phase HPLC. Active fractions were confirmed by Ultraviolet–Visible (UV–Vis) spectral fingerprints (≈230 nm) for hydroxamate, with a band at 430–450 nm upon Fe(III) complexation, as well as by chrome azurol A assay, Nuclear Magnetic Resonane (NMR) spectroscopy, High-Performance Liquid Chromatography–Mass Spectrometry (HPLC-MS), and Matrix-Assisted Laser Desorption/Ionization–Time-of-Flight Mass Spectrometry (MALDI-TOF-MS). CPGB exhibited strong molar absorptivity and rapid, concentration-dependent chelation of Fe(III), yielding a sustained binding profile that matched or exceeded that of DFO over time. In determining n-octanol/water partitioning for CPGB and DFO (230 nm) and their Fe(III) complexes, the partitioning (P) assay revealed that CPGB was moderately hydrophilic (P = 0.505 ± 0.063; cLogP = −0.299 ± 0.053), while DFO was strongly hydrophilic (P = 0.098 ± 0.005; cLogP = −1.010 ± 0.022). Fe(III) complexation reduced lipophilicity: CPGB–Fe partitioned ~30–35% into octanol, while DFO–Fe complex partitioned ~7–8%, remaining largely aqueous. Overall, this outcome potentially suggested improved clearance in vivo. These data nominate CPGB as a promising alternative to existing iron chelators. The siderophore exhibited greater lipophilicity, emphasizing better passive membrane permeability than DFO, while siderophore–Fe(III) binding indicated increased biases toward the aqueous phase. Future in vivo studies are warranted to confirm its pharmacokinetics, safety, and therapeutic efficacy. Full article

Alzheimer’s disease is driven by multiple molecular drivers, including the pathological behavior of two intrinsically disordered proteins, amyloid-β (Aβ) and tau, whose aggregation is regulated by sequence-encoded ensembles and liquid–liquid phase separation (LLPS). This review integrates recent advances in biophysics, structural biology, and computational modeling to provide a multiscale perspective on how sequence determinants, post-translational modifications, and protein dynamics regulate the conformational landscapes of Aβ and tau. We discuss sequence-to-ensemble principles, from charge patterning and aromatic binders to familial mutations that reprogram structural ensembles and modulate LLPS. Structural studies, including NMR, SAXS, cryo-EM, and cryo-electron tomography, trace transitions from disordered monomers to fibrils and tissue-level structures. We highlight experimental challenges in LLPS assays, emerging standards for reproducibility, e.g., LLPSDB, PhaSePro, and FUS benchmarks, and computational strategies to refine and condensate modeling. Finally, we explore the therapeutic implications, including condensate-aware medicinal chemistry, ensemble-driven docking, and novel insights from clinical trials of anti-Aβ antibodies. Together, these perspectives underscore a paradigm shift toward environment- and ensemble-aware therapeutic design for Alzheimer’s and related protein condensation disorders. Full article