Search Results (177)

Four 8-acyl-1-pyrrolidinylnaphalenes are prepared where the acyl group is pivaloyl (6), benzoyl (7), benzyloxycarbonyl (8), and ethyloxycarbonyl (9). Crystal structures for 6–8 show that both the carbonyl and pyrrolidinyl groups are nearly perpendicular to the naphthalene ring. Esters 8 and 9 fluoresce more strongly than ketones 6 and 7. All show some solvatofluoro-chromic emission from a charge-transfer excited state. Calculations suggest that both the acyl and amino groups twist back toward planarity with the naphthalene in the relaxed first singlet excited state. With 8 and 9, co-planarity is within 20°, while with 6 and 7, the carbonyl approaches no closer than 30°. With 6 and 7, the charge-transfer emission is replaced with a shorter wavelength band with more polar solvents. Despite the twisted geometries and steric interference toward planarization, these systems do not show emission from a twisted intramolecular charge-transfer (TICT) state. Full article

We developed a solvent-suppressed ¹H nuclear magnetic resonance (NMR) method for the quantitative analysis of the components of rotigotine prolonged-release microspheres prepared for injection. Dimethyl terephthalate was used as an internal standard and dimethylsulfoxide -d₆ as the solvent. The analysis was performed using a Bruker Avance III HD 600 MHz NMR spectrometer, employing the noesygppr1d pulse sequence at a controlled temperature of 25 °C. Nuclear magnetic resonance spectra were acquired with a relaxation delay time (D1) of 40 s to simultaneously determine the content of rotigotine and the excipients mannitol and stearic acid in the rotigotine prolonged-release microspheres. Using the proposed approach, we successfully quantified the active pharmaceutical ingredient rotigotine and excipients in the prolonged-release microspheres. This method demonstrated excellent linearity, high precision, and strong repeatability. The solvent-suppressed ¹H NMR method developed in this study allows for the simultaneous quantification of rotigotine and the key excipients mannitol and stearic acid in the prolonged-release microspheres. This approach is accurate, simple, efficient, and environmentally friendly. Full article

Developing high-performance bio-based epoxy resins as sustainable alternatives to petroleum-derived bisphenol A (BPA) epoxies for recyclable carbon fiber-reinforced polymers (CFRPs) is pivotal in materials research. Herein, the bio-based bisphenol monomer BDEF was synthesized from the lignin derivative 4-propylguaiacol. The derived epoxy monomer BDEF-EP was cured with adipic acid to form a bio-based vitrimer. Stress relaxation synergistically accelerates through intrinsic dynamic carboxylic acid ester exchange and enhanced chain mobility from the flexible propyl structure. At 220 °C, this vitrimer shows rapid stress relaxation (τ* < 30 s) and repairs ~90% of surface scratches in 30 min. It exhibits tensile and flexural strengths of 69 MPa and 105 MPa, respectively. BDEF-EP’s low viscosity reduces diluent needs in composite fabrication, lowering costs and improving efficiency. The resulting bio-based CFRP achieves tensile and flexural strengths of 543 MPa and 414 MPa, respectively, which are comparable to commercially available petroleum-derived CFRP. In addition, CFRP containing dynamic crosslinked networks demonstrates degradable recyclability in ethylene glycol solvent, preserving the surface morphology and chemical structure of recovered carbon fibers. The results demonstrate that this bio-based epoxy vitrimer has promising potential for developing sustainable, degradable, and recyclable CFRP composites. Full article

Pressure-sensitive adhesion arises at a specific rheological behavior of polymer systems, which should correlate with their relaxation properties, making them potentially useful for predicting and altering adhesive performance. This work systematically studied the rheology of eco-friendly pressure-sensitive adhesives based on non-crosslinked polyisobutylene ternary blends free of solvents and byproducts, which serve for reversible adhesive bonding. The ratio between individual polymer components differing in molecular weight affected the rheological, relaxation, and adhesion properties of the constituted adhesive blends, allowing for their tuning. The viscosity and viscoelasticity of the adhesives were studied using rotational rheometry, while their adhesive bonds with steel were examined by probe tack and shear lap tests at different temperatures. The adhesive bond durability at shear and pull-off detachments depended on the adhesive composition, temperature, and contact time under pressure. The double differentiation of the continuous relaxation spectra of the adhesives enabled the accurate determination of their characteristic relaxation times, which controlled the durability of the adhesive bonds. A universal linear correlation between the reduced failure time of adhesive bonds and their reduced formation time enabled the prediction of their durability with high precision (Pearson correlation coefficient = 0.958, p-value < 0.001) over at least a four-order-of-magnitude time range. The reduction in the formation/failure times of adhesive bonds was most accurately achieved using the longest relaxation time of the adhesives, associated with their highest-molecular-weight polyisobutylene component. Thus, the highest-molecular-weight polymer played a dominant role in adhesive performance, determining both the stress relaxation during the formation of adhesive bonds and their durability under applied load. In turn, this finding enables the prediction and improvement of adhesive bond durability by increasing the bond formation time (a durability rise by up to 10–100 times) and extending the adhesive’s longest relaxation time through elevating the molecular weight or proportion of its highest-molecular-weight component (a durability rise by 100–350%). Full article

In the quest for greener alternatives to conventional organic solvents, Deep Eutectic Solvents (DESs) have gained significant attention due to their sustainability, biodegradability, and tunability. The use of water as an active and genuine component has recently led to the emergence of water-based DESs (wb-DESs). Here, a careful experimental characterization was performed on choline acetate (ChAc)/water mixtures across a range of water:ChAc molar ratios (n = 2–6). Differential Scanning Calorimetry (DSC) revealed glass transitions between 150 and 180 K, with no first-order transitions, leading to a classification of these mixtures as Low Transition-Temperature Mixtures (LTTMs). Physicochemical measurements, including density, viscosity, electrical conductivity, and refractive index, were conducted over a broad temperature range. NMR analyses provided insights into dynamics and solvation environments, with ¹H T1_slow relaxation times reaching their lowest value at n = 2, consistent with the formation of a strong hydrogen-bonding network. The n = 2 mixture was further investigated using Small and Wide-Angle X-ray Scattering (S-WAXS) and ab initio molecular dynamics (AIMD). These studies, jointly with ¹H NMR choline diffusion coefficient, directly challenge previous claims of the existence of aggregation phenomena in wb-DES. The simulation revealed a well-organized solvation structure, where acetate and water synergistically stabilize the choline cation through a cooperative hydrogen-bonding network. These findings highlight the impact and significance of an integrated physicochemical study in guiding the rational development of new sustainable systems, such as wb-DESs. Full article

In this study, supramolecular inclusion complexes composed of komecosanol (Ko), a lipophilic compound derived from rice bran, and α-cyclodextrin (αCD) were prepared using a solvent-free three-dimensional (3D) ball milling method. Their physicochemical properties were examined using various techniques. Powder X-ray diffraction analysis of the ground mixture at a Ko/αCD ratio of 1/8 revealed the disappearance of diffraction peaks characteristic of Ko and the emergence of new peaks, indicating the formation of a distinct crystalline phase. Moreover, differential scanning calorimetry analysis showed the disappearance of the endothermic peaks corresponding to Ko, indicating molecular-level interactions with αCD. Near-infrared spectroscopy results suggested the formation of hydrogen bonds between the C–H groups of Ko and the O–H groups of αCD. Solid-state ¹³C CP/MAS NMR and T₁ relaxation time measurements indicated the formation of a pseudopolyrotaxane structure, while scanning electron microscopy images confirmed distinct morphological changes consistent with complex formation. These findings demonstrate that 3D ball milling facilitates the formation of Ko/αCD inclusion complexes with a supramolecular architecture, providing a novel approach to improve the formulation and bioavailability of poorly water-soluble lipophilic compounds. Full article

Background/Objectives: Tegoprazan (TPZ) is a potassium-competitive acid blocker (P-CAB) used to treat conditions such as gastroesophageal reflux disease, peptic ulcer, and Helicobacter pylori infection. It exists in three solid forms: amorphous, Polymorph A, and Polymorph B. This study investigates the molecular basis of polymorph selection, focusing on conformational bias and solvent-mediated phase transformations (SMPTs). Methods: The conformational energy landscapes of two TPZ tautomers were constructed using relaxed torsion scans with the OPLS4 force field and validated by nuclear Overhauser effect (NOE)-based nuclear magnetic resonance (NMR). Hydrogen-bonded dimers were analyzed using DFT-D. Powder X-ray diffraction (PXRD), differential scanning calorimetry (DSC), solubility, and slurry tests were conducted using methanol, acetone, and water. Kinetic profiles were modeled with the Kolmogorov–Johnson–Mehl–Avrami (KJMA) equation. Results: Polymorph A was thermodynamically stable across all analyses. Both amorphous TPZ and Polymorph B converted to A in a solvent-dependent manner. Methanol induced direct A formation, while acetone showed a B → A transition. Crystallization was guided by solution conformers and hydrogen bonding. Conclusions: TPZ polymorph selection is governed by solution-phase conformational preferences, tautomerism, and solvent-mediated hydrogen bonding. DFT-D and NMR analyses showed that protic solvents favor the direct crystallization of stable Polymorph A, while aprotic solvents promote the transient formation of metastable Polymorph B. Elevated temperatures and humidity accelerate polymorphic transitions. This crystal structure prediction (CSP)-independent strategy offers a practical framework for rational polymorph control and the mitigation of disappearing polymorph risks in tautomeric drugs. Full article

Water’s unique physicochemical properties arise from its dynamic hydrogen-bonding network, yet the precise molecular threshold at which these cooperative behaviors emerge remains a key question. This study employed nuclear magnetic resonance (NMR) spectroscopy and density functional theory (DFT) calculations to investigate the evolution of hydrogen bonding strength in small water clusters, ranging from dimers to pentamers. The observed exponential increase in NMR chemical shift up to the pentamer reflects growing hydrogen bond cooperativity, identifying the (H₂O)₅ cluster as a critical structural and energetic threshold. At this size, the network achieves sufficient connectivity to support key bulk-like phenomena such as proton transfer and dielectric relaxation. These conclusions were corroborated by complementary FT-IR and electrochemical impedance spectroscopy (EIS) measurements of bulk water. Our results position the water pentamer as the molecular onset of emergent solvent behavior, effectively bridging the divide between discrete clusters and the macroscopic properties of liquid water. Full article

Bis- and trisphosphines incorporating methylene and aryl spacers readily adsorb on the surface of porous activated carbon (AC). The adsorption can be performed in the absence of solvents, even when the phosphines have high melting points, or from solutions. The diverse phosphines Ph₂PCH₂PPh₂ (dppm), Ph₂P(CH₂)₂PPh₂ (dppe), Ph₂P(CH₂)₃PPh₂ (dppp), Ph₂P(p-C₆H₄)PPh₂ (dppbz), and (Ph₂PCH₂)₃CCH₃ (tdme) were adsorbed in submonolayers on AC. The adsorbed phosphines were studied by ³¹P MAS (magic angle spinning) NMR spectroscopy, and their mobilities on the surface were confirmed by determining the ³¹P T₁ relaxation times. All phosphine groups of each bis- and trisphosphine molecule are in contact with the surface, and the molecules exhibit translational mobility as one unit. All phosphines used here are air-stable. Once a submonolayer is created on the AC surface, oxygen from the air is co-adsorbed and transforms all phosphines quantitatively into phosphine oxides at room temperature. The oxidation proceeds in a consecutive manner with the oxidation of one phosphine group after another until the fully oxidized species are formed. Studies of the kinetics are based on integrating the signals in the solution ³¹P NMR spectra. High temperatures and low surface coverages increase the speed of the oxidation, while light and acid have no impact. The oxidation is fast and complete within one hour for 10% surface coverage at room temperature. In order to study the mechanism and slow down the oxidation, a higher surface coverage of 40% was applied. No unwanted P(V) side products or water adducts were observed. The clean phosphine oxides could be recovered in high yields by washing them off of the AC surface. The oxidation is based on radical activation of O₂ on the AC surface due to delocalized electrons on the AC surface. This is corroborated by the result that AIBN-derived radicals enable the air oxidation of PPh₃ in solution at 65 °C. When the air-stable complex (CO)₂Ni(PPh₃)₂ is applied to the AC surface and exposed to the air, OPPh₃ forms quantitatively. The new surface-assisted air oxidation of phosphines adsorbed on AC renders expensive and hazardous oxidizers obsolete and opens a synthetic pathway to the selective mono-oxidation of bis- and trisphosphines. Full article

Background/Objectives: Haloxylon griffithii is a medicinal plant possessing therapeutic effects in disorders associated with the gastrointestinal (GIT) system. This research aims to study the pharmacological activity of Haloxylon griffithii in a multidimensional manner, involving phytochemistry screening and in vitro and in vivo experiments. Methods: The whole dried plant was extracted with 80% methanol and further fractionation using solvents of increasing polarity. GC-MS analysis was performed on the crude extract to discover volatile compounds. The spasmolytic/spasmogenic effect was assessed in isolated rabbit jejunum using spontaneous and K⁺-induced contractions, as well as contractions induced by increasing concentrations of calcium ions in depolarized tissue. Antidiarrheal activity was evaluated in Swiss albino rats/mice (n = 6/group) using castor oil-induced diarrhea and peristaltic index models. In silico ADMET screening was conducted via SwissADME and pkCSM. Results: The GC-MS profiling of H. griffithii revealed the presence of 59 phytochemicals and a rare azulene derivative and constituents, including α-santonin and hexadecanoic acid esters, with favorable pharmacokinetic profiles, as predicted using SwissADME and pkCSM computational tools. The in vitro and in vivo experiments revealed the significant calcium channel blocking activity in non-polar fractions (n-hexane and ethyl acetate), while the polar extracts (ethanolic, aqueous) exhibited cholinergic effects, indicating a dual mode of action. Conclusions: This was a first-time demonstration of both antidiarrheal and smooth muscle-relaxant activity in H. griffithii, supported by GC-MS profiling and pharmacological assay. The findings lend scientific credibility to the traditional use of the plant in community healthcare, while also reinforcing the need for further pharmacological and clinical studies to explore its potential in drug development. Full article

The effects of proline co-solvent on helix folding are explored through the single discrete coordinate of the number of helical hydrogen bonds. The analysis is based on multi-microsecond length molecular dynamics simulations of alanine-based helix-forming peptides, (ALA)n, of length n = 4, 8, 15 and 21 residues, in an aqueous solution with 2 M concentration of proline. The effects of addition of proline on the free energy landscape for helix folding were analyzed using the graph-based Dijkstra algorithm, Optimal Dimensionality Reduction kinetic coarse graining, committor functions, as well as through the diffusion of the helix boundary. Viewed at a sufficiently long time-scale, helix folding in the coarse-grained hydrogen bond space follows a consecutive mechanism, with well-defined initiation and propagation phases, and an interesting set of intermediates. Proline addition slows down the folding relaxation of all four peptides, increases helix content and induces subtle mechanistic changes compared to pure water solvation. A general trend is for transition state shift towards earlier stages of folding in proline relative to water. For ALA5 and ALA8 direct folding is dominant. In ALA8 and ALA15 multiple pathways appear possible. For ALA21 a simple mechanism emerges, with a single path from helix to coil through a set of intermediates. Overall, this work provides new insights into effects of proline co-solvent on helix folding, complementary to more standard approaches based on three-dimensional molecular structures. Full article

QM/MM simulations were performed to investigate the ionizations of four DNA nucleotides in the explicit solution. The vertical ionization energies (VIEs) and adiabatic ionization energies (AIEs) were averaged over 40 snapshots to calculate mean values. The QM/MM VIEs (6.92–7.63 eV) were ~0.70 eV lower than those of the corresponding nucleosides. This suggests that the water environment cannot fully screen the effect of the phosphate group on ionizations. The result is inconsistent with computations using implicit solvent models. The distributions of holes in both adiabatic and vertical ionizations suggest that bulk-water polarization drives the hole transfer from first-shell water to nucleobases, resulting in increases in VIEs and AIEs. Moreover, we computed the released energies in the structural relaxations after ionizations. The results indicate that the minimal energies are released by the structural relaxations of both the bulk-water and the QM region. The redistributions of the electron density on first-shell water molecules and nucleobases produce the primary contributions to released energies. Full article

Proteins and their surrounding hydration water engage in a dynamic interplay that is critical for maintaining structural stability and functional integrity. However, the intricate coupling between protein dynamics and the structural order of hydration water remains poorly understood. Here, we employ all-atom molecular dynamics simulations to investigate this relationship across four representative proteins. Our results reveal that protein residues with greater flexibility or solvent exposure are surrounded by more disordered hydration water, akin to bulk water, whereas rigid and buried non-polar residues are associated with structurally ordered hydration shells. Due to their strong hydrogen bonding and electrostatic interactions, charged residues exhibit the most disordered hydration water, while non-polar residues are associated with the structurally most ordered hydration water. We further uncovered a positive correlation between the relaxation dynamics of protein residues and their hydration water: slower (faster) protein relaxation is coupled with slower (faster) relaxation of the structural order of hydration water. Notably, this coupling weakens with increasing residue flexibility or solvent exposure, with non-polar residues displaying the strongest coupling, and charged residues the weakest. To further uncover their coupling mechanism, we elucidate residue-specific coupled fluctuations between protein residues and hydration water by generating scatter plots. These findings provide a comprehensive understanding of the mechanisms underlying protein–water interactions, offering valuable insights into the role of hydration water in protein stability, dynamics, and function. Full article

Organometallic rare-earth complexes have attracted considerable attention in recent years due to their unique structures and exceptional magnetic properties. In this study, we report the synthesis and magnetic characteristics of a family of monopentamethylcyclopentadienyl-coordinated trinuclear rare-earth hepta-chloride clusters [(Li(THF)(Et₂O))(Cp^*RE)₃(μ-Cl)₄(μ₃-Cl)₂(μ₄-Cl)] (RE₃: RE =Y, Gd, Tb, Dy, Ho, Er, Tm, Yb, Lu; Cp* = pentamethylcyclopentadienide). These clusters were synthesized by reacting LiCp* with RECl₃ in a 1:1 molar ratio within a mixed solvent system (THF: Et₂O = 1:9), resulting in high solubility in common organic solvents such as DCM, THF, and Et₂O. Magnetic studies conducted on these paramagnetic clusters reveal the coexistence of ferromagnetic and antiferromagnetic superexchange interactions in Gd₃. Additionally, Dy₃ exhibits both ferromagnetic and antiferromagnetic intramolecular dipolar interactions. Notably, slow magnetic relaxation was observed in Dy₃ below 23 K under a zero DC applied field with an energy barrier of 125(6) cm⁻¹. Full article

The heat generation characteristics of magnetic nanoparticles (NPs) induced by an alternating magnetic field (AMF) while simultaneously exposed to a DC magnetic field are crucial for the clinical application of magnetic fluid hyperthermia integrated with magnetic particle imaging. In this study, we investigated the dependence of the specific absorption rate (SAR) of magnetite and cobalt (Co) ferrite NP suspensions on a static transverse DC magnetic field under an applied AMF. The results showed that the SAR of Co ferrite NPs remained unaffected by the DC magnetic field, whereas that of magnetite NPs gradually decreased as the DC magnetic field increased. Furthermore, the SAR of magnetite NPs dispersed in high-viscosity solvents was somewhat lower than that of particles dispersed in water, while the SAR of Co ferrite NPs was significantly reduced. These findings can be explained by differences in the Néel relaxation time, which arise from variations in magnetic anisotropy. Full article