Search Results (1,296)

Understanding Li⁺ solvation structure is critical for the rational design of high- and localized high-concentration electrolytes. Here, we present a systematic investigation of tetrahydrofuran (THF)-based electrolytes with lithium bis(trifluoromethanesulfonyl)imide (LiTFSI) using Raman spectroscopy and ⁷Li nuclear magnetic resonance to investigate the local solvation structures. By varying the THF:LiTFSI molar ratio, we observed a transition of Li⁺ solvation from solvent-separated ion pairs to contact ion pairs and aggregates, accompanied by increased structural heterogeneity and constrained local dynamics. Raman spectroscopy captures the evolution of Li⁺–anion coordination with increasing salt concentration, while ⁷Li NMR chemical shifts, line widths, and relaxation times provide complementary insight into changes in the electronic environment and symmetry of Li⁺ coordination. Electrolyte structure is further examined by introducing a hydrofluoroether co-solvent into a concentrated (THF)₂–LiTFSI electrolyte. Raman results show that the local Li⁺–TFSI⁻ coordination structure is preserved upon 1,1,2,2-tetrafluoroethyl-2,2,3,3-tetrafluoropropyl ether (TTE) addition, whereas NMR reveals subtle modifications of the ion-rich solvation clusters. These results provide fundamental insight into Li⁺ solvation and electrolyte localization, offering general design principles for advanced electrolyte systems. Full article

Liquid–liquid phase separation (LLPS) underlies the formation of membraneless cellular compartments, yet experimental strategies that directly connect quantitative LLPS behavior with residue-level structural information remain limited. Here, we present an integrated protocol that combines quantitative LLPS assays with nuclear magnetic resonance (NMR) spectroscopy and structure-guided mutagenesis to regulate protein phase separation. Using the VAPB MSP domain as a representative example, this workflow links residue-specific structural features to macroscopic LLPS behavior and enables suppression or enhancement of phase separation through targeted amino acid substitutions. This protocol provides a generalizable framework for systematic, residue-level regulation of protein LLPS. Full article

Background: Pentamidine isethionate (PTM) and miltefosine (MF) are clinically relevant antiparasitic agents whose use is limited by toxicity, emerging resistance, and the lack of effective co-delivery strategies. Tetronic^® 1307 (T1307), an amphiphilic and thermoresponsive block copolymer, was investigated as a carrier to enable their combination therapy. Methods: PTM and MF were formulated in T1307-based micelles and thermoresponsive gels. The systems were characterized by small-angle neutron scattering (SANS), dynamic light scattering (DLS), and nuclear magnetic resonance spectroscopy (NMR). Antiparasitic activity was evaluated against Leishmania major promastigotes. Results: MF formed stable micelles that efficiently incorporated PTM, generating a “drug-in-drug” architecture. While T1307 alone showed limited PTM loading, MF promoted mixed micelle formation and enhanced PTM incorporation. At physiological temperature and adequate copolymer concentrations, drug-loaded micelles formed thermoreversible gels suitable for topical application. The combined formulations preserved drug activity and exhibited synergistic effects against L. major. Conclusions: T1307 is a promising platform for the co-delivery of PTM and MF, enabling synergistic combination therapy and thermoresponsive gel formation with potential to reduce systemic toxicity and improve treatment administration. Full article

Hydroxyl-terminated polybutadiene (HTPB) propellants are widely used in aerospace applications owing to their excellent mechanical performance and storage stability, which are primarily governed by the crosslinked network formed during curing. Understanding the evolution of this network is therefore essential for optimizing propellant formulations and curing parameters. In this work, the curing behaviors of HTPB-based propellant slurries employing two representative curing agents, toluene diisocyanate (TDI) and isophorone diisocyanate (IPDI), were systematically investigated under isothermal conditions at 60 °C using low-field nuclear magnetic resonance (LF-NMR), combined with infrared spectroscopy, dynamic mechanical analysis, and macroscopic mechanical testing. The curing time and crosslink density of both propellant systems were quantitatively determined by LF-NMR crosslink densitometry, while transverse relaxation time measurements were used to monitor the mobility evolution of different molecular segments during curing. The results show that with increasing curing time, the crosslink density and crosslinked chain content progressively increased, whereas the free chain content decreased, accompanied by a transient increase and subsequent decrease in dangling chains. The curing endpoints of the HTPB/TDI and HTPB/IPDI propellants were determined to be approximately 1.25 days and 5.5 days, with corresponding final crosslink densities of 2.438 × 10⁻⁴ and 2.007 × 10⁻⁴ mol mL⁻¹, respectively. Excellent agreement between LF-NMR results and complementary characterization techniques confirms LF-NMR as an effective tool for studying curing reaction and network evolution in complex solid propellant systems. Full article

Thymosin β4 (Tβ4) is a highly acidic, intrinsically disordered 43-amino-acid peptide with diverse biological functions, yet its interactions with metal ions remain poorly understood. In this study, we provide the first experimental demonstration that Tβ4 forms discrete Zn²⁺-bound adducts and undergoes Zn²⁺-induced aggregation under physiological pH conditions. Combining zeta potential analysis, dynamic light scattering (DLS), electrospray ionization mass spectrometry (ESI-MS), nuclear magnetic resonance (NMR) spectroscopy, and scanning electron microscopy with elemental mapping (SEM/EDS), we show that Zn(II) binding progressively neutralizes Tβ4’s negative surface charge and triggers a sharp aggregation transition. ESI-MS unambiguously identifies Tβ4/Zn(II) complexes of peptide-to-zinc molar ratio 1:3, while DLS and SEM reveal the formation of compact, low-solubility supramolecular assemblies. NMR measurements support a metal-induced aggregation, confirming the absence of folding upon Zn(II) binding. By quantitatively comparing the experimentally determined critical aggregation concentration with physiologically observed extracellular Zn(II) ranges, we demonstrate that aggregation is unlikely in plasma or basal interstitial environments but may become feasible in Zn-rich microdomains, such as the synaptic cleft, where transient Zn(II) levels can exceed 1 μM. These findings introduce a previously unrecognized dimension of Tβ4 chemistry and suggest that a Zn(II)-mediated supramolecular assembly of Tβ4 could influence peptide behavior in neurological or inflammatory conditions characterized by elevated extracellular Zn(II). This work establishes a foundational biochemical framework for future studies aimed at elucidating the biological implications of Tβ4/Zn(II) complexation and aggregation in vivo. Full article

Tight conglomerate reservoirs exhibit strong pore-scale heterogeneity and extremely low permeability, in which spontaneous imbibition is primarily governed by capillary and viscoelastic effects. In this study, the imbibition dynamics of four representative fracturing fluid systems, including slickwater, 3% potassium chloride (KCl) brine, hydrolyzed polyacrylamide (HPAM) viscoelastic fluid, and a nanoemulsion (NE), were investigated using a temperature-controlled nuclear magnetic resonance (NMR) monitoring system. This approach enables real-time quantification of fluid uptake and pore-scale redistribution through time-resolved T₂ spectral analysis. The experimental results reveal a three-stage imbibition process consisting of rapid capillary-driven uptake, viscoelastic-retarded transition, and final equilibrium. Among the four fracturing fluid systems, the nanoemulsion exhibits the lowest interfacial tension (1.72 mN/m), the strongest wettability alteration, and the highest equilibrium recovery (0.76), which is nearly 80% greater than that of slickwater. Based on these observations, a multiscale capillary–viscoelastic coupling model was developed by extending the Lucas–Washburn framework to incorporate pore-size distribution, time-dependent wettability evolution, and viscoelastic damping. The model fits the experimental data well (R² > 0.90) and identifies viscosity as the most influential parameter controlling the imbibition rate (sensitivity = 0.78). Energy analysis further indicates that capillary energy dominates the early stage, whereas viscoelastic energy storage sustains fluid transport during the later stage. SEM observations were further used to qualitatively corroborate pore heterogeneity and pore–mineral associations, supporting the NMR-based pore-scale interpretation. This study provides a quantitative framework for describing non-Newtonian capillary flow in tight conglomerate rocks and enhances the understanding of capillary–viscoelastic interactions relevant to multiphase fluid migration. Full article

Pomegranate peel, accounting for 35–50% of the fruit weight, is an underutilized agri-food by-product. This study applied, for the first time, fermentation with Saccharomyces cerevisiae as a simple and sustainable strategy to simultaneously obtain tannin-rich extracts and polysaccharide fractions with potential prebiotic activity. Peels from two cultivars, Wonderful and G1, differing in peel thickness, were subjected to three fermentation protocols (air- and not air-exposed) and monitored at 25 °C over 48 and 72 h. HPLC-DAD analysis showed that yeast-inoculated fermentation increased total tannin concentration in dry extracts (up to 70%) without inducing chemical modifications to tannin profiles. As determined by Dynamic Light Scattering, fermentation promoted significant depolymerization of native polysaccharides, while DOSY-¹H-NMR analyses revealed the presence of reduced molecular weight fractions down to 26 kDa. In vitro growth assays confirmed that fermented polysaccharides were more efficiently utilized as a carbon source by Bifidobacterium breve and Lactiplantibacillus plantarum compared to non-fermented controls, likely thanks to polysaccharide depolymerization induced by fermentation. The study demonstrated that air-exposed S. cerevisiae fermentation was an effective process alternative to chemical or enzymatic hydrolysis for modifying pomegranate peel pectin directly within a complex matrix, while simultaneously enhancing tannin recovery. This approach represents a possible sustainable strategy for pomegranate peel valorization into functional ingredients. Full article

Soil organic matter (SOM) molecular composition governs its stability and ecological functions in forest ecosystems. Nevertheless, how land-use changes (LUCs) regulate the SOM molecular composition remains poorly understood, particularly the underlying mechanisms mediated by soil properties. This study investigated the effects of LUCs on SOM molecular composition in a subtropical coastal region and examined the driving roles of soil nutrient availability and enzyme activities. The research was conducted in Huanghai National Forest Park, Jiangsu Province, China, focusing on four land-use types converted from historical wheat cropland (W, as control): monoculture plantations of Ginkgo biloba (G) and Metasequoia glyptostroboides (M), a ginkgo–metasequoia mixed forest (GM), and a ginkgo–wheat agroforestry system (GW). Soil samples were collected from 0 to 20 cm and 20–40 cm layers and analyzed for SOM molecular compositions using solid-state ¹³C nuclear magnetic resonance (NMR) spectroscopy. Soil chemical properties and enzyme activity activities were also determined, with redundancy analysis (RDA) and correlation analysis applied to identify key influencing factors. Results demonstrated that LUCs significantly altered SOM molecular composition. The GW system exhibited the highest proportion of labile O-alkyl carbon (42.65%), while the M plantation accumulated greatest levels of stable aromatic carbon (up to 49.25%). During the initial decades following afforestation, soil nutrient availability and enzyme activities were confirmed as pivotal drivers of SOM molecular variation. Specifically, available potassium (AK), ammonium nitrogen (AN), and the carbon/phosphorus (C/P) ratio were significantly correlated with specific SOM components (p < 0.05). The elevated O-alkyl carbon proportion in GW was closely associated with its higher invertase activity. Notably, vertical differentiation in SOM stability was observed across land-use types, with the agroforestry system achieving the highest carbon pool management index in surface soil but showing a weakened capacity for subsoil C stabilization. RDA further confirmed that AK and AN were dominant factors shaping SOM molecular composition. In conclusion, LUCs modulate SOM chemical composition and stability primarily through altering soil nutrient availability and associated enzyme activities. Agroforestry system facilitates labile C accumulation in surface soil, whereas monoculture plantations are more conducive to stable C sequestration, especially in subsoil layers. These findings provide novel mechanistic insights into SOM dynamics following LUCs and offer a theoretical basis for formulating tailored management strategies to enhance C sequestration efficiency in subtropical coastal ecosystems. Full article

Alginate is a widely used and versatile biopolymer with an ever-expanding range of applications in the pharmaceutical and biomedical industries. This highlights the importance of developing sustainable and renewable production sources. Conventional extraction methods, although effective, are often energy-intensive and rely on harsh chemicals. In this context, brown algae are a promising alternative due to their abundance and renewability. This study investigated the potential of Saccorhiza polyschides and Sargassum muticum as sources of sodium alginate (SA), thus optimising an extraction process that combines acid treatment with an alkaline step. The extracted biopolymers were characterised using FTIR, H-NMR, STA, SEM/EDX, viscosity measurements, dynamic light scattering, and spectrophotometric assays of residual polyphenols and proteins. The optimised extraction conditions produced yields above 20% of high-purity alginate. When compared with commercial SA, the extracted materials showed comparable quality while relying on a simplified, solvent-reduced protocol that improves process efficiency and reduces the environmental impact. These results demonstrate that S. polyschides and S. muticum are promising, locally available sources of high-quality sodium alginate, and that industrially relevant yields (>20%) can be achieved through an environmentally conscious two-step extraction process. Full article

Poly(hexamethylene biguanide) (PHMB) is a polycationic antimicrobial polymer exhibiting broad-spectrum activity against bacteria, fungi, and viruses, and is widely used in medical settings for infection prevention and control. However, the relationship between chemical structure and antimicrobial activity remains unclear. In this study, we synthesised and characterised a series of polymeric biguanides with systematically varied alkyl chain lengths to examine the effects of structural variation on physicochemical properties and antimicrobial activity. H NMR spectroscopy and FTIR confirmed successful polymerisation. Solubility measurements revealed a progressive decrease in aqueous solubility with increasing alkyl chain length, consistent with increased hydrophobicity. Dynamic light scattering indicated reversible folding and unfolding of polymer chains in aqueous solution, with stabilisation at higher concentrations. Diffusion-ordered spectroscopy was used to calculate hydrodynamic diameters and polydispersity indices. Antimicrobial assays against Staphylococcus aureus and Pseudomonas aeruginosa showed that polymers containing heptamethylene and octamethylene chains exhibited the highest antibacterial activity, whereas tetramethylene- and pentamethylene-containing polymers showed greater fungicidal activity against Candida albicans. Highly hydrophobic polymers showed increased aggregation, resulting in reduced antimicrobial efficacy. Overall, these results indicate that both charge density and alkyl chain length are key determinants of antimicrobial activity. This polymeric biguanide series provides a platform for further investigation of structure–activity relationships and mechanisms of action against pathogenic microorganisms and their biofilms. Full article

Background/Objectives: Pyrazole carboxamides are widely used as adaptable medicinal-chemistry scaffolds and have been explored as cholinesterase (ChE) inhibitor chemotypes. In this work, we prepared a new series of 4-arylazo-3,5-diamino-N-tosyl-1H-pyrazole-1-carboxamides 5(a–m) and evaluated their inhibitory activity against acetylcholinesterase (AChE) and butyrylcholinesterase (BChE), supported by structure-based computational analyses. Methods: Thirteen derivatives 5(a–m) were synthesized, fully characterized with analytical techniques (FT-IR, H NMR, and C NMR), and tested in vitro against AChE and BChE, with tacrine (THA) used as the reference inhibitor. Docking calculations were used to examine plausible binding modes. The top-ranked complexes (7XN1–5e and 4BDS–5i) were further examined by 100 ns explicit-solvent molecular dynamics (MD) simulations in Cresset Flare, followed by RMSD/RMSF analysis and contact-persistence profiling. Predicted ADME/Tox. properties were also assessed to identify potential developability issues. Results: The series showed strong ChE inhibition, and several compounds were more potent than THA. Compound 5e (4-nitro) was the most active AChE inhibitor (K_I = 20.86 ± 1.61 nM) compared with THA (K_I = 164.40 ± 20.84 nM). For BChE, the K_I values ranged from 31.21 to 87.07 nM and exceeded the reference compound’s activity. MD trajectories supported stable binding in both systems (10–100 ns mean backbone RMSD: 2.21 ± 0.17 Å for 7XN1–5e; 1.89 ± 0.11 Å for 4BDS–5i). Most fluctuations were confined to flexible regions, while key contacts remained in place, consistent with the docking models. ADME/Tox. predictions suggested moderate lipophilicity but generally low aqueous solubility; all compounds were predicted as non-BBB permeant, and selected liabilities were flagged (e.g., carcinogenicity for 5e/5g/5h/5i; nephrotoxicity for 5f/5g). Conclusions: The 4-arylazo-3,5-diamino-N-tosyl-1H-pyrazole-1-carboxamide scaffold delivers low-nanomolar ChE inhibition, with docking and MD supporting stable binding modes. Future optimization should prioritize solubility improvement and mitigation of predicted toxicities and metabolic liabilities, especially given the predicted lack of BBB permeability for CNS-directed applications. Full article

Polyurethane-based implantable devices (PUIDs) delivered via catheter are increasingly used in structural heart interventions; however, limited in vivo data exist regarding their long-term biostability and biological safety. This study evaluated a balloon-shaped implant made of Pellethane^®, a polyether-based polyurethane, designed as a three-dimensional intracardiac spacer and deployed via percutaneous femoral vein access. The device was chronically positioned adjacent to the tricuspid valve annulus in seven pigs for 24 weeks. Explanted devices and surrounding tissues were evaluated through material characterization (SEM, GPC, FT-IR, and ¹H-NMR) and histological analysis. SEM and FT-IR confirmed preserved surface morphology and chemical bonds, GPC showed stable molecular weight, and ¹H-NMR revealed intact urethane and ether linkages. Materials characterization revealed no evidence of hydrolytic or oxidative degradation, indicating structural stability of the devices. Histological analysis showed stable device positioning with minimal thrombosis or inflammatory response. Biocompatibility was confirmed via ISO 10993-1:2018 Standard (International Organization for Standardization (ISO): Geneva, Switzerland, 2018), and extractable substances were evaluated under exhaustive extraction conditions specified by ISO 10993-18:2020 (International Organization for Standardization (ISO): Geneva, Switzerland, 2020), with no toxicologically significant findings. These findings support the long-term biostability and biological safety of the PUIDs in dynamic cardiac environments, informing future design criteria for catheter-delivered cardiovascular devices. Full article

This study investigates the interface between cement hydration, low-field NMR relaxometry, and the incorporation of carbon-based fillers into cementitious materials. The objective is to provide NMR-based insights into how carbon black (CB) and an acrylic superplasticizer (SP) influence cement hydration and the resulting microstructural evolution. CB was integrated into white Portland cement (WPC) using both wet and dry mixing approaches, with water content and SP dosage varied independently. First, water-based “inks” containing different SP/CB weight ratios were prepared and evaluated through dynamic light scattering (DLS) and ζ-potential measurements to assess colloidal stability and dispersibility. For the wet-mixing route, an in situ NMR experiment was performed to monitor the progressive incorporation of carbon ink into cement pastes while increasing the water content. The ability to distinguish ink-related signals from those originating from the cement paste represents a promising step toward non-destructive assessments of carbon dispersion in fresh pastes. Separately, ex situ NMR measurements were performed on samples extracted from dry-mixed pastes with various SP dosages. These experiments mark the SP-induced delay in hydration and the refinement of the pore network that is also associated with improved particle dispersion. Complementary optical microscopy (OM) and ultrasonic pulse velocity (UPV) measurements on hardened samples corroborate the NMR findings. Full article

Cutaneous leishmaniasis (CL) is a neglected tropical disease for which current chemotherapeutic options are limited by systemic toxicity (such as hepato-nephrotoxicity, arrhythmia, nausea, vomiting) and difficult administration regimens. Pentamidine (PTM), although effective, exhibits severe dose-limiting adverse effects. Polymeric micelles based on Pluronic^® F127 (F127) offer an attractive strategy to improve PTM delivery by enhancing solubility, reducing cytotoxicity, and enabling controlled release. Here, we developed PTM-loaded F127 polymeric micelles and performed a multidisciplinary evaluation combining physicochemical characterization, in vitro biological assays, and gene expression profiling. Dynamic light scattering, UV–visible absorption, fluorescence spectroscopy, and NMR confirmed micelle formation, PTM–polymer interactions, and temperature-dependent assembly. PTM-loaded micelles exhibited biorelevant nanoscale dimensions and preserved stability under physiological conditions. Biological assays demonstrated that F127 micelles markedly reduced PTM cytotoxicity in RAW264.7 macrophages while maintaining potent antileishmanial activity against Leishmania major promastigotes. RT-qPCR analysis revealed modulation of key pathways involved in redox homeostasis, oxidative stress, calcium regulation, apoptosis-like responses, and drug resistance, suggesting that micellar encapsulation influences both PTM bioavailability and parasite stress responses. Overall, PTM-loaded F127 micelles significantly improved the therapeutic index of PTM in vitro. These findings support the potential of F127 polymeric micelles as a promising nanocarrier platform for safer and more effective CL therapy. Full article

Background/Objectives: First row transition metal ions have recently regained attention in coordination chemistry as alternatives to gadolinium-based paramagnetic contrast agents, motivated by emerging safety concerns associated with certain Gd³⁺-based contrast agents. In this study, we report the development of a novel homoleptic diketonate Fe³⁺ complex functionalized with biocompatible indole moieties. We investigate its potential as a paramagnetic relaxation agent by evaluating its ability to modulate the T₁ and T₂ relaxation times of water proton. Methods: Iron(III) tris-1,3-(1-methylindol-3-yl)propanedionate [Fe(BIP)₃] was synthesized via a thermal method from bis(1-methylindol-3-yl)-1,3-propanedione (HBIP) using Fe(ClO₄)₃∙6 H₂O as the metal source. The complex was characterized by UV-Vis, IR and NMR spectroscopy, differential scanning calorimetry–thermogravimetric analysis, and single-crystal X-ray diffraction. Fe(BIP)₃ aggregation behavior in aqueous environment, including size and morphology of aggregates, was investigated using dynamic light scattering and scanning electron microscopy. Incorporation of the aggregates into phospholipid vesicles was evaluated by fluorescence resonance energy transfer and fluorescence correlation spectroscopy. The paramagnetic properties of monomeric Fe(BIP)₃ were probed in solution by nuclear magnetic resonance recurring to the Evans bulk magnetization method. Results: The designed synthetic procedure successfully afforded Fe(BIP)₃, which was fully characterized by UV-Vis and IR spectroscopy, as well as single-crystal X-ray diffraction. Aqueous solutions of Fe(BIP)₃ spontaneously formed rice-grain-shaped nanoscale aggregates of hydrodynamic radius ≈ 30 nm. Incorporation of these aggregates into phospholipid vesicles enhanced their stability. The longitudinal r₁ and transverse r₂ relaxivities of Fe(BIP)₃ aggregates were assessed to be 1.92 and 52.3 mM⁻¹s⁻¹, respectively, revealing their potential as paramagnetic relaxation agents. Conclusions: Fe(BIP)₃ aggregates, stabilized through incorporation into phospholipid vesicles, demonstrate promising potential as novel paramagnetic relaxation agents in aqueous environments. Full article