Chelation Of Cations Research Articles

Dual-Substitution Strategy Utilizing Cation Chelation and Assembly Process to Realize Solid Solution Reaction in Layered Oxide Cathode for Na-Ion Batteries.

Na0.67Ni0.33Mn0.67O2 (NNM) is regarded as a promising cathode material for Na-ion batteries (NIBs), but suffers from irreversible phase transformations characterized by multiple voltage plateaus, resulting in poor cycle stability and inferior rate capability. To address these issues, the Na0.67Ni0.18Cu0.10Zn0.05Mn0.67O2 (NNCZM) cathode material is synthesized by a cation chelation and reassembly process, which can promote a more uniform element distribution than that prepared by the solid-state method (S-NNCZM), resulting in better Na+ diffusion kinetics and rate capability. Replacing Ni2+ with a small amount of Zn2+ prevents the P2-O2 phase transformation, while replacing Ni2+ with an appropriate amount of electrochemically active Cu2+ eliminates Na-vacancy ordering and additionally contributes to capacity. Thus, the dual substitution of Cu2+ and Zn2+ for Ni2+ makes the NNCZM electrode synergistically achieve a complete solid solution reaction and better cycling stability. Accordingly, it exhibits a large discharge capacity (110.2 mA h g-1 at 10 mA g-1) with a high initial coulombic efficiency (97.3%), remarkable cycle stability with 84.1% capacity retention over 200 cycles at 200 mA g-1, and excellent rate capability with a discharge capacity of 61.0 mA h g-1 at 2000 mA g-1, significantly outperforming the NNM and S-NNCZM electrodes.

Ni-Co nano-alloys confined by N-doped porous carbon overlayer to boost hydrodeoxygenation of 5-hydroxymethylfurfural

Ni-Co nano-alloys confined by in-situ formed N-doped porous carbon overlayer have been prepared through chelation of metal cations with citric acid and urea followed by carbonization for hydrodeoxygenation of 5-hydroxymethylfurfural (HMF) into 2, 5-dimethylfuran (DMF). The results indicated that the Ni-Co nano-alloys were formed and homogeneously distributed within the N-doped porous carbon overlayer. The electronic effect of the Ni-Co nano-alloys significantly boosted hydrodeoxygenation activity of the Co2Ni1@NC catalyst and simultaneously inhibited further hydrogenation and opening of furan ring. The N-doped porous carbon overlayer around Ni-Co nano-alloys not only facilitated to disperse and stable Ni-Co nano-alloys through strong metal-support interaction, but also protected the Ni-Co nano-alloys from aggregation. Therefore, the Co2Ni1@NC catalyst offered superior catalytic performance with the HMF conversion of 100 % and DMF selectivity of 93.0 %. Moreover, the Co2Ni1@NC catalyst displayed excellent stability without significant activity loss after five recycles due to the spatial confinement of N-doped carbon overlayer.

Green-assisted synthesis of highly defective nanostructured Fe-doped SnO2: Magnetic and photocatalytic properties evaluation

Here we present a comprehensive characterization of the properties of undoped and Fe-doped SnO2 nanoparticles prepared with Syzygium cumini leaves extract. The phytochemicals present in the leaves extract act as cation chelating and capping of the nanoparticles. It is observed a relative high concentration of tin (up to 10 %) and oxygen (up to 5%) vacancies promoted by surface adsorbed OH− and by Fe-doping, respectively. The magnetic characterization reveals a ferromagnetic with a saturation monetization up to 20×10−3 emu/g for the higher defective and Fe-doped sample. This behavior associated mainly to tin vacancies for the undoped samples, and to the formation of bound magnetic polarons between the incorporated Fe and the oxygen vacancies for the doped samples. Oxygen vacancies and incorporated Fe improve the SnO2 photocatalytic efficiency in the visible range of the electromagnetic spectrum by decreasing the SnO2 effective bandgap from 3.6 eV for the undoped SnO2 sample to only 1.9 eV for the Fe-doped SnO2 sample, and by acting as electron-trapping centers increasing the system quantum efficiency. Due to the ferromagnetic behavior of the studied samples, it was also considered the effect of spin-dependent processes in the observed photocatalytic improvement. Our results highlight the key role of defect engineering strategies to optimize the physical and chemical properties of semiconductor oxides for application in the development of spintronic and quantum information devices, and in systems devoted to wastewater purification through advanced oxidation processes.

Understanding Mechanisms and Key Factors Influencing Melanogenesis for the Management of Melasma: An Updated Review.

Melanocytes are highly specialized dendritic cells that deliver melanin to keratinocytes in melanosomes, which are subcellular organelles where melanin is produced and stored. Mammal's skin, hair, and eyes all contain the complex pigment melanin, which gives them color and ultraviolet protection. Melanins have the potential to be free radical sinks and are strong cation chelators. Amino acid tyrosine and its metabolite, dopa, are the precursors to complex metabolic processes that end with melanin production. Melanocytes generate different types and amounts of melanin, which is defined genetically and is impacted by several extrinsic and intrinsic factors such as hormone fluctuations, inflammation, age, and ultraviolet radiation exposure, leading to the stimulation of numerous melanogenesis pathways. Melasma, a common skin pigmentation condition, is associated with the overproduction of melanin and is characterized by brown to gray-brown and black spots that mostly affect the face. The present review addresses the regulatory mechanisms and signaling pathways involved in skin pigmentation with an emphasis on the altered melanogenesis that causes melasma and hyperpigmentation. The current study also illustrates the available treatment options with cellular and molecular mechanisms for the management of melasma. Understanding the mechanism of the pigmentation process may help researchers develop new therapeutic strategies and novel drugs for the management of melasma.

A moldable hydrogel based on sericin and Zn2+/F- dual-doped hydroxyapatite promotes skull defect repair through the synergistic effects of immunoregulation, enhanced angiogenesis and osteogenesis

Skull defect repair typically involves multiple stages, including immunomodulation, angiogenesis, osteogenic differentiation, and biomineralization, etc. Most existing therapeutic biomaterials fail to show functional effects across all these stages, leading to unsatisfactory repair effects. To address this challenge, an organic–inorganic hybrid HT(SA)HAp moldable hydrogel with the aforementioned functional properties was developed. The moldable hydrogel consisted of phenylboronic acid-grafted hyaluronic acid, tannic acid, alendronate sodium-grafted sericin (Ser-AL), and hydroxyapatite co-doped with 5 % Zn and 10 % F (Zn5%/F10%-HAp). These materials were cross-linked due to phenylborate ester bonds, metal-phenol interactions, and the AL-mediated chelation of divalent metal cations. Sericin-mediated immunomodulation serves as a precursor to micro-environmental regulation, reducing inflammation at the site of injury and creating an environment conducive to angiogenesis and osteogenic differentiation. The degradation products of the hydrogel’s organic skeleton promoted the proliferation of mesenchymal stem cells and vascular endothelial cells. The enhanced paracrine effect of mesenchymal stem cells and the release of Zn2+ from modified Zn5%/F10%-HAp promoted angiogenesis, while the degradation products of these materials ensured continued promotion of osteogenic differentiation and biomineralization. This organic–inorganic hybrid hydrogel had the synergistic effects of immunoregulation, enhanced angiogenesis, osteogenic differentiation, and biomineralization, which could significantly accelerate the repair of skull defects, and demonstrate completely repaired skull defects at 8 weeks. Thus, this multifunctional moldable hydrogel provided an effective and stable treatment strategy for the rapid repair of skull defects.

Tunable Oxidized-Chitin Hydrogels with Customizable Mechanical Properties by Metal or Hydrogen Ion Exposure.

This study focuses on the optimization of chitin oxidation in C6 to carboxylic acid and its use to obtain a hydrogel with tunable resistance. After the optimization, water-soluble crystalline β-chitin fibrils (β-chitOx) with a degree of functionalization of 10% were obtained. Diverse reaction conditions were also tested for α-chitin, which showed a lower reactivity and a slower reaction kinetic. After that, a set of hydrogels was synthesized from β-chitOx 1 wt.% at pH 9, inducing the gelation by sonication. These hydrogels were exposed to different environments, such as different amounts of Ca2+, Na+ or Mg2+ solutions, buffered environments such as pH 9, PBS, pH 5, and pH 1, and pure water. These hydrogels were characterized using rheology, XRPD, SEM, and FT-IR. The notable feature of these hydrogels is their ability to be strengthened through cation chelation, being metal cations or hydrogen ions, with a five- to tenfold increase in their storage modulus (G'). The ions were theorized to alter the hydrogen-bonding network of the polymer and intercalate in chitin's crystal structure along the a-axis. On the other hand, the hydrogel dissolved at pH 9 and pure water. These bio-based tunable hydrogels represent an intriguing material suitable for biomedical applications.

Removal of Heavy Metals from Contaminated Aquatic Streams Using a Resin Supported Green nZVI

This study addresses the escalating demand for clean water resources driven by population growth and water quality deterioration. The research focuses on evaluating the efficacy of a nanocomposite material, incorporating zero valent iron nanoparticles into a chelating cation exchange resin matrix, for selectively removing heavy metals from polluted aquatic environments. The selected resin, featuring iminodiacetic acid functional groups, demonstrates notable selectivity for heavy metal cations over alkali earth metals. Column experiments were conducted to assess the nanocomposite’s performance, utilizing a feed solution spiked with heavy metals at concentrations ten times higher than Greek legislation limits for wastewater effluent recycling. The nanocomposite exhibited significant effectiveness for Cu, Cr(VI), and Pb, consistently maintaining Cu levels below detection limits and demonstrating limited breakthrough of Cr(VI) and Pb depending on experimental conditions. However, the removal efficiency was lower for Ni and insufficient for Cd, Zn, and As in this complex multicomponent solution. This research contributes valuable insights into the potential application of the developed nanocomposite for targeted removal of specific heavy metals in contaminated water sources, providing a foundation for further exploration and application in water remediation technologies.

Synthesis, Antioxidant and Antituberculosis Evaluation of Eugenol Derivatives from Mannich Condensation

AbstractMannich bases are interesting class of molecules thanks to their various pharmacological properties. This paper presents the synthesis and characterization of eugenol derivatives following Mannich condensation. The in vitro antituberculosis activity of the synthesized derivatives was evaluated by the Resazurin microtiter assay (REMA). The 2,2′‐diphenyl‐1‐picrylhydrazyl (DPPH) free radical scavenging and ferrous cation (FeCl2) chelating tests were used to estimate the antioxidant capacity. All eugenol Mannich bases inhibited the Mycobacterium tuberculosis (Mtb) H37Rv growing. Those of 2‐dimethylaminomethyl‐6‐methoxy‐4‐propenylphenol (1) and 2‐methoxy‐4‐propenyl‐6‐pyrrolidinylmethylphenol (4) were the most active at 10 μg/mL. Additionally, significant antioxidant profile was exhibited by the synthesized derivatives, especially for 2‐dicyclohexylaminomethyl‐6‐methoxy‐4‐propenylphenol (5) that showed an antiradical activity of EC50=20 μg/mL, twice as strong as that of eugenol precursor, and for 2‐methoxy‐6‐methylpiperazinylmethyl‐4‐propenylphenol (3) and compound 4, which were promising iron chelators with EC50 of 0.016 and 0.018 mg/mL, respectively, better than EDTA standard. The molecular docking experiments on two different antituberculosis receptors showed excellent binding affinity of compounds 4 and 5 into the active site of pantothenate kinase (PanK, type I), suggesting PanK as potential molecular target. These encouraging findings showed the importance of Mannich reaction for the development of antitubercular candidates and the improvement of natural products bioactivity.

Human plasma inositol hexakisphosphate (InsP 6 ) phosphatase identified as the Multiple Inositol Polyphosphate Phosphatase 1 (MINPP1).

Inositol hexakisphosphate (InsP 6 ), also known as phytic acid, is a potent chelator of bivalent cations. Intracellular InsP 6 molecules are associated with magnesium. Calcium is the prevalent bivalent cation outside the cell and its association with InsP 6 could lead to the formation of insoluble complexes. To avoid the formation of dangerous InsP 6 /Calcium precipitates in the bloodstream, mammals must possess a robust InsP 6 phosphatase in their plasma. Here we identify the Multiple Inositol Polyphosphate Phosphatase 1 ( MINPP1 ) as the InsP 6 phosphatase present in human plasma.

Unraveling the mystery: Extraction and component analysis of irrecoverable foulants of end-of-life membrane from large-scale MBR

Membrane bioreactors (MBRs) are increasingly employed in municipal wastewater treatment, with membranes inevitably reaching their end-of-life (EOL) primarily due to the accumulation of irrecoverable fouling. Nevertheless, the composition and properties of irrecoverable fouling remain ambiguous due to the lack of appropriate extraction and analytical methods. Herein, we developed a temperature-regulated organic solvent extraction method to extract and analyze irrecoverable foulants in EOL ultrafiltration membranes at various locations within a large-scale MBR for municipal wastewater treatment. The irrecoverable foulants encompassed a high molecular weight fraction not observed in the influent, potentially induced by aggregation from organic-inorganic foulant interaction. The terrestrial humic acid (HA)-like substance dominated the organic components of irrecoverable foulants, and the chelating cation Ca emerged as a dominant inorganic compound. Unexpectedly, we noticed the enrichment of Al, Fe, and Si in the irrecoverable fouling, despite their relatively low rejections by the EOL membrane. The potential complex interactions among HA-like substances, Ca, Al, Fe, and Si were revealed by correlation and cluster analysis. The strong bridging potentials of [Al(OH)4]-, Fe(OH)3 at neutral pH, coupled with the colloidal property of Si, may facilitate the aggregation of organic and inorganic compounds, forming complex irrecoverable foulants with strong affinity for the membrane matrix. Besides, the irrecoverable fouling exhibited an increasing trend along the water flow direction. The mystery of irrecoverable fouling of EOL membrane was, for the first time, systematically unraveled, establishing a foundation for the development of effective membrane cleaning and regeneration technology.

Macrocyclic Ligand Coordinating Amide-Arm Hydrolysis Reaction Activation in Aqueous Solutions: Tetravalent Uranium Does It Better.

Chelation of lanthanide and actinide cations within a suitable macrocyclic ligand often results in a rigid, kinetically inert, and thermodynamically stable complex. A benchmark for such cation-ligand suitability are cyclen-derived macrocyclic ligands, frequently used as large cation hosts for various applications. Herein, a comprehensive study of the 1,4,7,10-tetrakis(carbamoylmethyl)-1,4,7,10-tetraazacyclododecane ligand (DOTAM) chelates of UIV and CeIII and their properties in aqueous solutions is presented. By employing multiple analysis techniques, including X-ray crystallography, UV-vis absorbance, 1H NMR, UPLC-MS, cyclic voltammetry, and differential pulse voltammetry, the study has revealed that the two aqueous complexes undergo a spontaneous, gradual, and stepwise hydrolysis of each of the coordinated amides toward carboxylates. The coordination of UIV in the studied reaction has been shown to significantly enhance the reaction rate, leading to an acceleration of up to 6 orders of magnitude compared to the natural process of simple aqueous amides at room temperature. An attempt to describe the unusual chelated metal cation amide-activation feature, based on the relatively lower rigidity of the complex structure, is presented. Additionally, the electrochemical properties of the complex series are discussed in detail, along with the limitations of the analytical methods employed.

Degree of complexation of microelement ions by biodegradable IDHA chelator in water and simulated fertilization environment

Abstract The degree of complexation of microelement ions by the biodegradable chelating agent - IDHA was examined in the work. The tests were carried out in water and in a simulated fertilizer environment. In order to compare the obtained results, tests were also carried out for the commonly used EDTA. The performed analyzes allow to determine the influence of the presence of compounds containing macroelements on the degree of binding of microelement ions by the biodegradable IDHA and EDTA chelators. The obtained results make it possible to determine the optimal conditions for the chelation of cations by IDHA, which in the future may be used in the production of micronutrient fertilizers on a large scale.

Effects of thermal hydrolysis process-generated melanoidins on partial nitritation/anammox in full-scale installations treating waste activated sludge

Thermal hydrolysis process (THP) is a well-established anaerobic digestion (AD) pre-treatment technology. Despite the THP benefits the pre-treatment increases the concentrations of nutrients and melanoidins in the digestate reject water after dewatering. The increased concentrations of nutrients and melanoidins formed during THP-AD can impact downstream processes, such as struvite precipitation and partial nitritation/anammox (PN/A). In our present work, six full-scale PN/A influents and effluents were sampled in The Netherlands (4 with THP and 2 without THP). Full-scale samples were characterised and the stoichiometric O2 consumption and melanoidins chelated to trace elements were analysed. The results showed that THP increased the concentration of total ammoniacal nitrogen (TAN), chemical oxygen demand (COD), total organic carbon (TOC), UVA 254 and colour, which are indicators of melanoidins occurrence. THP furthermore decreased the stoichiometric NO3−-N production from the PN/A reaction in effluents. The disparity between stoichiometric and measured NO3− -N in the THP-using plants was explained by the proliferation of denitrifiers. Moreover, denitrification improved the N removal efficiency due to the consumption of the stoichiometrically-produced NO3− -N. Also, the stoichiometric O2 consumption increased in the plants using THP, reaching up to 56% of the O2 used for partial oxidation of TAN. Trace elements analysis revealed that the plants with elevated concentrations of melanoidins in the effluent showed a high percentage of chelated multivalent cations, particularly transition metals such as Fe. Kendall correlation coefficient analysis showed that the chelation of multivalent cations was correlated mainly with colour occurrence in the reject waters. Overall, the results indicated that in PN/A systems using THP-AD increased O2 consumption and trace elements availability should be considered during the process design.

Extractable latex yield from Taraxacum kok-saghyz roots is enhanced by increasing rubber particle buoyancy

Taraxacum kok-saghyz (TK) is a leading alternative rubber-producing plant that produces natural rubber (NR) latex in laticifers within its roots. Unlike the tropical rubber tree, Hevea brasiliensis, TK can be grown in temperate regions, such as the northern United States, as the basis of a domestic rubber production industry. To support such an industry, efficient, scalable rubber extraction techniques are needed. In this study, aqueous extraction was used to recover TK natural rubber latex (TNRL) from four harvests of greenhouse-produced TK roots with a new technique that improves rubber particle buoyancy in root homogenate by chelation. The new method includes harvest, cleaning, and homogenization of freshly harvested roots, followed by centrifugation, vacuum collection of latex, and purification. Treatment of homogenate with ethylenediaminetetraacetic acid (EDTA), a divalent cation chelator, allowed more than twice as much latex to be extracted from fresh homogenate. EDTA-treated rubber particles contained lower concentrations of divalent cations than untreated ones in fresh homogenate and homogenate stored for two weeks. Long term (three months) storage of root homogenate similarly yielded more latex than fresh homogenate and had low divalent cation rubber particle concentrations, indicating that heavy cations had slowly leached from the particles into the aqueous medium during storage. Rubber particle size was larger in this treatment suggestive of rubber particle agglomeration but this was prevented and reversed by EDTA. Removal of divalent cations via chelation increased particle packing density of particles in concentrated latex and appeared to increase the gel content of dried latex samples. Molecular characterization of dried samples of purified TNRL established that the rubber was of the high molecular weight needed for product manufacturing.

Biosensor-guided detection of outer membrane-specific antimicrobial activity against Pseudomonas aeruginosa from fungal cultures and medicinal plant extracts.

Pseudomonas aeruginosa responds to sub-lethal antimicrobial exposure by inducing the expression of lipopolysaccharide (LPS) surface modifications that mask antibiotic binding sites and contribute to repair and resistance of the outer membrane (OM). We exploit these membrane damage-responsive operons in a biosensor approach used to discover new antimicrobials that specifically target the OM. Chromosomal transcriptional luxCDABE reporters from the pmr (polymyxin resistance; aminoarabinose LPS modification) and speD2E2 (spermidine synthesis) operons are induced by validated outer membrane-acting agents including cationic antimicrobial peptides, cation chelators, ascorbic acid, detergents, and cell wall synthesis inhibitors cycloserine and bacitracin. To identify novel sources of OM-disrupting antimicrobials, we used these OM damage-responsive biosensors to screen a panel of fungal culture supernatants for novel antimicrobial and biosensor activity. Biosensor activity was used to determine the optimal time point of antimicrobial production from fungal supernatants and to guide the purification of active fractions after size-exclusion chromatography. Water and ethanol extracts of Chinese medicinal plants also proved to be a source of biosensor activity. The pathogen box is a 400-member drug library of potential antimicrobials, but none of these compounds induced our OM damage biosensors. This novel, sensitive, cell-based screening assay has potential for future discovery of lead compounds that specifically target the outer membrane, which is a significant barrier to antibiotic entry into Gram-negative bacteria.IMPORTANCENew approaches are needed to discover novel antimicrobials, particularly antibiotics that target the Gram-negative outer membrane. By exploiting bacterial sensing and responses to outer membrane (OM) damage, we used a biosensor approach consisting of polymyxin resistance gene transcriptional reporters to screen natural products and a small drug library for biosensor activity that indicates damage to the OM. The diverse antimicrobial compounds that cause induction of the polymyxin resistance genes, which correlates with outer membrane damage, suggest that these LPS and surface modifications also function in short-term repair to sublethal exposure and are required against broad membrane stress conditions.

Determining gas-phase chelation of zinc, cadmium, and copper cations with HisHis dipeptide using action spectroscopy and theoretical calculations

Using light generated by an infrared free electron laser, action spectroscopy was performed on doubly charged complexes of the metalated dipeptide histidyl-histidine (HisHis). Metal cations used were zinc, cadmium, and copper. Molecular dynamics and quantum-chemical calculations were used to screen a large number of conformers, whose theoretical infrared spectra were compared to the recorded action spectra of these metalated complexes. The zinc and cadmium spectra display dominant features associated with an iminol binding motif of the HisHis ligand, where the metal ion coordinates with both pros (π) nitrogens of the imidazole sidechains, the terminal carbonyl oxygen, and the backbone nitrogen for which the hydrogen ordinarily bound here has migrated to a carbonyl. The copper complex was difficult to assign to a single species, because a few predicted bands are absent from the experimental spectrum. The theoretical single point energies were also calculated for all structures examined, and DFT methods were found to describe the ion conformer populations in the case of the zinc and cadmium chelates better than the MP2 prediction.

Mechanism of Lactiplantibacillus plantarum regulating Ca2+ affecting the replication of PEDV in small intestinal epithelial cells.

Porcine epidemic diarrhea virus (PEDV) mainly invades the small intestine and promotes an inflammatory response, eventually leading to severe diarrhea, vomiting, dehydration, and even death of piglets, which seriously threatens the economic development of pig farming. In recent years, researchers have found that probiotics can improve the intestinal microenvironment and reduce diarrhea. At the same time, certain probiotics have been shown to have antiviral effects; however, their mechanisms are different. Herein, we aimed to investigate the inhibitory effect of Lactiplantibacillus plantarum supernatant (LP-1S) on PEDV and its mechanism. We used IPEC-J2 cells as a model to assess the inhibitory effect of LP-1S on PEDV and to further investigate the relationship between LP-1S, Ca2+, and PEDV. The results showed that a divalent cation chelating agent (EGTA) and calcium channel inhibitors (Bepridil hydrochloride and BAPTA-acetoxymethylate) could inhibit PEDV proliferation while effectively reducing the intracellular Ca2+ concentration. Furthermore, LP-1S could reduce PEDV-induced loss of calcium channel proteins (TRPV6 and PMCA1b), alleviate intracellular Ca2+ accumulation caused by PEDV infection, and promote the balance of intra- and extracellular Ca2+ concentrations, thereby inhibiting PEDV proliferation. In summary, we found that LP-1S has potential therapeutic value against PEDV, which is realized by modulating Ca2+. This provides a potential new drug to treat PEDV infection.

Preparation of amide oxime type surfactants and the chelation of copper and nickel cations

Preparation of amide oxime type surfactants and the chelation of copper and nickel cations

Mechanistic understanding of the effect of sodium citrate soaking of red kidney beans on their cooking behaviour

In this study, the role of soaking beans in a sodium citrate solution (a cation chelator) at pH = 4.4 and 41 °C in directing/improving the cooking behaviour of common beans was explored. The cooking behaviour of the pre-soaked red kidney beans was determined and the corresponding changes of phytate, minerals, starch, protein and pectin were quantified. Soaking beans in citrate buffer could accelerate softening of the beans during cooking in deionised water while subsequent cooking of beans in this buffer had a limited additional effect on softening compared to cooking in deionised water. Phytate hydrolysis during soaking in citrate buffer results in a release of Mg2+ and Ca2+. Both cations were leached into the soaking medium, higher amounts being observed for Mg2+ release to the soaking media because of the lower affinity of Mg2+ for pectin. It was observed that the pectin solubilisation rate in beans treated by sodium citrate buffer was positively correlated to bean softening. All of these results point out that soaking in a citrate buffer prohibits pectin Ca2+ cross linking therefore enhancing pectin solubilisation and thus increasing the bean softening rate constants during cooking, while starch and protein were not responsible for texture evolution.

Epithelium dynamics differ in time and space when exposed to the permeation enhancers penetramax and EGTA. A head-to-head mechanistic comparison

Absorption of therapeutic peptides like glucagon-like peptide or insulin for diabetes therapy upon oral administration is highly restricted by the tight junction (TJ) proteins interconnecting the cells comprising the intestinal epithelium. An approach to improve transepithelial permeation of such biopharmaceuticals via the paracellular pathway is to use functional excipients, which transiently modulate the TJs. Here, we investigated the membrane-interacting peptide, penetramax, and the divalent cation chelator, ethylene glycol tetraacetic acid (EGTA) at different concentrations, to reveal and compare their cellular modes of action when increasing the transepithelial permeation of drug macromolecules. The epithelial integrity was studied in real time along with dextran permeation across differentiated epithelial Caco-2 cell monolayers. TJ protein expression and cytoskeleton organization were investigated during and after exposure to penetramax or EGTA. Based on orthogonal methods, we show that penetramax acts by a mechanism that immediately and transiently widens the paracellular space, resulting in size selective permeant passage and with subsequent reconstitution of the epithelium. At the same time, the expression and organization of different TJ proteins are modulated reversibly. In contrast, the effect of EGTA on modulating the paracellular space is slower and TJ protein unspecific, and without clear permeant size selectivity. Overall, these data provide in-depth insights for understanding intestinal barrier dynamics of importance when evaluating new or existing excipients for oral delivery of biopharmaceuticals, such as peptide therapeutics.