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Synthetic branched-chain glycolipidsare suitable as model systemsin understanding biological cell membranes, particularly because certainnatural lipids possess chain branching. Herein, four branched-chainglycopyranosides, namely, 2-hexyl-decyl-α-d-glucopyranoside(α-Glc–OC10C6), 2-hexyl-decyl-β-d-glucopyranoside (β-Glc–OC10C6), 2-hexyl-decyl-α-d-galactopyranoside (α-Gal–OC10C6), and 2-hexyl-decyl-β-d-galactopyranoside(β-Gal–OC10C6), with a total alkylchain length of 16 carbon atoms have been synthesized, and their phasebehavior has been studied. The partial binary phase diagrams of thesenonionic surfactants in water were investigated by optical polarizingmicroscopy (OPM) and small-angle X-ray scattering (SAXS). The introductionof chain branching in the hydrocarbon chain region is shown to resultin the formation of inverse structures such as inverse hexagonal andinverse bicontinuous cubic phases. A comparison of the four compoundsshowed that they exhibited different polymorphism, especially in thethermotropic state, as a result of contributions from anomeric andepimeric effects according to their stereochemistry. The neat α-Glc–OC10C6compound exhibited a lamellar (Lα) phase whereas dry α-Gal–OC10C6formed an inverse bicontinuous cubic Ia3d(QIIG) phase. Both β-anomersof glucoside and galactoside adopted the inverse hexagonal phase (HII) in the dry state. Generally, in the presence of water,all four glycolipids formed inverse bicontinuous cubic Ia3d(QIIG) and Pn3m(QIID) phases over widetemperature and concentration ranges. The formation of inverse nonlamellarphases by these Guerbet branched-chain glycosides confirms their potentialas materials for novel biotechnological applications such as drugdelivery and crystallization of membrane proteins. [ABSTRACT FROM AUTHOR]

Water-driven self-assembly of lipids displays a varietyof liquidcrystalline phases that are crucial for membrane functions. Herein,we characterize the temperature-induced phase transitions in two compositionsof an aqueous self-assembly system of the octyl β-d-glucoside (βGlcOC8) system, usingsteady-state and time-resolved fluorescence measurements. The phasetransitions hexagonal ↔ micellar and cubic ↔ lamellarwere investigated using tryptophan (Trp) and two of its ester derivatives(Trp-C4and Trp-C8) to probe the polar headgroupregion and pyrene to probe the hydrophobic tail region. The polarityof the headgroup region was estimated to be close to that of simplealcohols (methanol and ethanol) for all phases. The pyrene fluorescenceindicates that the pyrene molecules are dispersed among the tailsof the hydrophobic region, yet remain in close proximity to the polarhead groups. Comparing the present results with our previously reportedone for βMaltoOC12, increasing thetail length of the hexagonal phase from C8to C12leads to less interaction with pyrene, which is attributed to themore random and wobbling motion of the longer alkyl tail. We measureda reduction (more hydrophobic) in the ratio of the vibronic peak intensitiesof pyrene (I1/I3) for the lamellar phase compared to that of the cubic phase. Thehigher polarity in the cubic phase can be correlated to the natureof its interface, which curves toward the bulk water. This geometryalso explains the slight reduction in polarity of the headgroup regioncompared to the other phases. Upon the addition of Trp-C8, the fluorescence lifetime of pyrene is reduced by 28% in the lamellarand cubic phases, whereas the I1/I3value is only slightly reduced. The resultsreflect the dominant role of dynamic interaction mechanism betweenthe C8chain of Trp-C8and pyrene. This mechanismmay be important for these two phases since they participate in theprocess of membrane fusion. Both lipid compositions show completelyreversible temperature-induced phase transitions, reflecting the thermodynamicequilibrium structures of their mesophases. Probing both regions ofthe different lipid phases reveals a large degree of heterogeneityand flexibility of the lipid self-assembly. These properties are crucialfor carrying out different biological functions such as the abilityto accommodate various molecular sizes. [ABSTRACT FROM AUTHOR]

Ranunculus hirtellus , also known as crowfoot (buttercup), has a rich tradition of use in various biological contexts. While antibacterial studies on extracts from this plant have been conducted, the phytochemical composition, antioxidant properties, and antidiabetic effects remain unexplored. In this study, the phytochemical, antioxidant, and antidiabetic effects of its methanol and aqueous extracts were investigated. Our approach involved gas chromatography-mass spectrometry (GC/MS), alongside quantitative and qualitative methods, for phytochemical profiles. Additionally, concerning biological activities, the antioxidant effect was assessed through 2, 2-diphenyl-pieryl hydrazyl (DPPH) and 2, 2'-azino-bis (3-ethylbenzothiazoline-6-sulfonate) (ABTS) assays, while the antidiabetic effect was examined through the α-amylase inhibitory assay. The chloroform, ethyl acetate, and n -hexane extracts of R. hirtellus revealed the presence of 14 distinct compounds. In the methanol extract, sterols, quinones, glycosides, lactones, lignin, and flavonoids were identified. The aqueous extract contained sterols, alkaloids, glycosides, triterpenes, terpenoids, quinones, leucoanthocyanins, and lactones. The total flavonoid content (TFC), total phenolic content (TPC), total tannin content (TTC), and reducing sugar content (RDC) were determined in plant extracts, and a linear relationship was found between these parameters. Additionally, the TTC, TPC, and TFC values for both extracts hovered around 0.3786, 0.0476, and 0.1864 μg/mL, respectively, across all plant concentrations, while RDC ranged from 0.9336 to 1.0119 μg/mL in all four extracts. In vitro assays demonstrated dose-dependent antidiabetic activity in both methanolic and aqueous extracts by inhibiting α-amylase. Furthermore, the antioxidant activity observed in the DPPH assay was greater in the aqueous extract compared with the methanolic extract. In addition, the ethyl acetate extract exhibited the highest inhibition among chloroform and n -hexane in the ABTS assay. The results suggest that R. hirtellus can be a potential source of natural antioxidants and antidiabetic agents, and further studies are warranted to investigate the underlying mechanisms of its therapeutic effects., Competing Interests: The authors declare no competing financial interest., (© 2024 The Authors. Published by American Chemical Society.)

Plant-mediated nanoparticles are gaining popularity due to biologically active secondary metabolites that aid in green synthesis. This study describes a simple, environmentally friendly, dependable, and cost-effective production of silver nanoparticles utilizing Cucumis sativus and Aloe vera aqueous leaf extracts. The aqueous leaf extracts of Cucumis sativus and Aloe vera , which worked as a reducing and capping agent, were used to biosynthesize silver nanoparticles (AgNPs). The formation of surface plasmon resonance peaks at 403 and 405 nm corresponds to the formation of colloidal Ag nanoparticles. Similarly, the Bragg reflection peaks in X-ray diffraction patterns observed at 2θ values of 38.01°, 43.98°, 64.24°, and 77.12° representing the planes of [111], [200], [220], and [311] correspond to the face-centered cubic crystal structure of silver nanoparticles. Fourier transform infrared spectroscopy confirms that bioactive chemicals are responsible for the capping of biogenic silver nanoparticles. The size, structure, and morphology of AgNPs with diameters ranging from 8 to 15 nm were examined using transmission electron microscopy. Water contamination by azo dyes and nitrophenols is becoming a more significant threat every day. The catalytic breakdown of organic azo dye methyl orange (MO) and the conversion of para -nitrophenol (PNP) into para -aminophenol using sodium borohydride was evaluated using the prepared biogenic nanoparticles. Our nanoparticles showed excellent reduction ability against PNP and MO with rate constants of 1.51 × 10 -3 and 6.03 × 10 -4 s -1 , respectively. The antibacterial activity of the nanomaterials was also tested against four bacteria: Staphylococcus aureus , Klebsiella pneumoniae , Enterobacter , and Streptococcus pneumoniae . These biogenic AgNPs displayed effective catalytic and antibacterial characteristics by reducing MO and PNP and decreasing bacterial growth., Competing Interests: The authors declare no competing financial interest., (© 2022 The Authors. Published by American Chemical Society.)

The lyotropic phase behavior of four common and easily accessible glycosides, n -octyl α-d-glycosides, namely, α-Glc-OC 8 , α-Man-OC 8 , α-Gal-OC 8 , and α-Xyl-OC 8 , was investigated. The presence of normal hexagonal (H I ), bicontinuous cubic (V I ), and lamellar (L α ) phases in α-Glc-OC 8 and α-Man-OC 8 including their phase diagrams in water reported previously was verified by deuterium nuclear magnetic resonance ( 2 H NMR), via monitoring the D 2 O spectra. Additionally, the partial binary phase diagrams and the liquid crystal structures formed by α-Gal-OC 8 and α-Xyl-OC 8 in D 2 O were constructed and confirmed using small- and wide-angle X-ray scattering and 2 H NMR. The average number of bound water molecules ( n b ) per headgroup in the L α phase was determined by the systematic measurement of the quadrupolar splitting of D 2 O over a wide range of molar ratio values (glycoside/D 2 O), especially at high glucoside composition. The number of bound water molecules bound to the headgroup was found to be around 1.5-2.0 for glucoside, mannoside, and galactoside, all of which possesses four OH groups. In the case of xyloside, which has only three OH groups, the bound water content is ∼2.0. Our findings confirmed that the bound water content of all n -octyl α-d-glycosides studied is lower compared to the number of possible hydrogen bonding sites possibly due to the fact that most of the OH groups are involved in intralayer interaction that holds the lipid assembly together.

New designer biofluorophores are being increasingly used in the investigation of complex cellular processes. In this study, we utilized new derivatives of pyrene (Py), i.e., 2- n -alkyl-pyrenes (Py-C 4 and Py-C 8 ), in order to probe different regions inside the hydrophobic tail of n -dodecyl β-d-maltoside (βMal-C 12 ) in two different phases (cubic ↔ lamellar). Although the sensitivity to the local environment is reduced compared to that of Py, attaching C 4 and C 8 at the 2-position of Py can provide a possible means to probe the local hydrophobicity in different parts of the tail region. The absence of excimer fluorescence and the ratio of the vibronic fluorescence peak intensities ( I 1 / I 3 ) in a lipid environment indicate the existence of Py as monomers in the hydrophobic region, similar to hydrophobic solvation, yet close to the headgroup region. When Py is replaced by Py-C 4 and Py-C 8 , there is a small increase in hydrophobicity (reduction in I 1 / I 3 ) as the Py moiety is pulled deeper inside the tail region of both cubic and lamellar phases. The larger space of the tail region in the lamellar phase is reflected as more local hydrophobicity measured by the probes which can penetrate deep inside, whereas the curved structure of the cubic phase limits the available space for the probes. Three fluorescence lifetime components were measured in lipid, indicating the heterogeneous nature of the hydrophobic region. In the lamellar phase, a large reduction in the average lifetime value, led by the long decay component, was measured for Py-C 4 (reduction by 25%) and Py-C 8 (45%) compared to that of the parent Py. This observation suggests the presence of a mechanism of interaction more collisional than static between the Py moiety and the tail region of the bilayer unit due to the ample space provided by the lamellar phase as the probe is buried deeper inside the hydrophobic region. A much smaller effect was observed in the cubic phase and was correlated with the tight environment around the probes, which stems from the increased curvature of the cubic phase. The current results provide a deeper understanding of the hydrophobic region during phase transition of lipid self-assembly which is important for better control during the process of membrane-protein crystallization.

Five synthetic β-d-maltosides derived from Guerbet branched alcohols, whose total hydrocarbon chain length ranged from C 8 to C 24 , were synthesized to a high anomeric purity, and their thermal properties, liquid-crystalline phases, and structures were characterized using differential scanning calorimetry, optical polarizing microscopy, and small-angle X-ray scattering. Thermal investigations of all anhydrous Guerbet maltosides showed that they do not form solid crystals but undergo a glass transition upon temperature change in the range of 35-53 °C. The glassy crystalline structure turns into the liquid-crystalline structure upon heating or addition of water. In thermotropic studies, the lamellar phase formation is prominent in shorter-chain-length analogues, whereas the longer-chain compounds exhibit a more frustrated form of self-assembly in the formation of a metastable state, polymorphism, and inverse bicontinuous cubic structure ( Ia3 d). The excess water conditions show that the phase formation is dominated by the lamellar phase for the longer-chain compounds. Normal micellar solution was observed in the shortest-chain-length maltosides because of the enlargement of hydrated maltose headgroups. The self-assembly of both dry and fully hydrated Guerbet maltosides, which exhibited glass-forming abilities and showed surface activity and also the ability to act as membrane-stabilizing compounds, makes them ideal candidates for practical use in industry as well as biomedical research.

Fluorescence upconversion and transient absorption techniques are used to explain the source of the intense red/near-infrared emission of crystalline 4-dimethylamino-2'-hydroxychalcone. We found that the initially excited enol form undergoes tautomerization in 3 ps to form the keto tautomer. The latter is stable in the ground state as a consequence of J-type aggregation in the crystal packing and is manifested in an absorption peak at 550 nm that spectrally overlaps with the short-lived enol emission, leading to self-reabsorption and adding a factor to the complete depletion of the enol emission. Relaxation of the keto tautomer takes place in the form of intense fluorescence (600-750 nm) with 1.7 ns lifetime. The different spectroscopy in solution is due to vibrational cooling (300 fs), followed by solvation dynamics (5 ps in methanol) and twisting of the hydroxyphenyl ring (16 ps), before relaxation of the enol tautomer in the form of weak green fluorescence with 350 ps lifetime.

The composite effects of gum arabic (GA) (5, 10, 15, and 20%) and chitosan (CH) (1.0%) on the biochemical and physiological characteristics of banana fruits stored at 13 ± 1 °C and 80 ± 3% relative humidity (RH) for 28 days and afterward for 5 days at simulated marketing conditions (25 °C, 60% RH) were investigated. Significant (P ≤ 0.05) differences were observed for the entire GA plus CH treatments as compared to the control. However, the results showed that after 33 days of storage, the weight loss and soluble solids concentration of fruits treated with 10% GA plus 1.0% CH composite coating were 24 and 54% lower, whereas fruit firmness, total carbohydrates, and reducing sugars were 31, 59, and 40% higher than the control, respectively. Furthermore, the composite edible coating of 10% GA plus 1.0% CH delayed color development and reduced the rate of respiration and ethylene evolution during storage as compared to the control. Similarly, sensory evaluation results also proved the effectiveness of 10% GA plus 1.0% CH composite coating by maintaining the overall quality of banana fruits. Consequently, the results of scanning electron microscopy also confirmed that the fruits coated with 10% GA plus 1.0% CH composite edible coating had very fewer cracks and showed a smooth surface. These findings suggest that 10% GA plus 1.0% CH as an edible composite coating can be used commercially for extending the storage life of banana fruits for up to 33 days.

Covalent binding of drug reactive metabolites to neutrophils or their precursors is thought to play a role in the development of drug-induced agranulocytosis. In this study, we used immunochemical techniques to compare the covalent binding of clozapine, vesnarinone, and procainamide (three drugs associated with agranulocytosis) to phorbol-12,13-myristate acetate (PMA)-activated human neutrophils in vitro and rat tissues in vivo. In PMA-activated human neutrophils in vitro, clozapine and procainamide modified neutrophil proteins with molecular masses ranging from 30 to 200 kDa, while vesnarinone predominately formed adducts with molecular masses greater than 70 kDa. All three drugs formed adducts at 126, 98, and 58 kDa, and they all covalently bound to human myeloperoxidase when incubated with this enzyme and H2O2 in vitro. Covalent binding to PMA-activated neutrophils was inhibited by nucleophiles, such as glutathione and N-acetylcysteine, but not by N-acetyllysine. In the presence of the PMA, all three drugs covalently bound to activated rat bone marrow cells in vitro, while in its absence only clozapine did. Covalently modified liver proteins were observed in rats treated for 6 weeks with clozapine (25 or 50 mg/kg/day), vesnarinone (300 mg/kg/day), or procainamide (50 mg/kg/day). Clozapine extensively modified proteins in all subcellular fractions; procainamide formed a 99 kDa adduct in a membrane-containing fraction and 57, 47, and 36 kDa adducts in a cytosolic fraction, while vesnarinone formed liver-protein adducts with molecular masses of 82, 62, 49, and 40 kDa in membrane, cytosolic, and S9 fractions. In addition, clozapine and procainamide, but not vesnarinone, formed a 49 kDa drug-protein adduct in the bone marrow of treated rats. Furthermore, procainamide covalently bound to a 58 kDa protein in neutrophils of a patient treated with the drug. We suspect that covalent modification of common targets in the neutrophils by these three drugs plays a role in the development of drug-induced agranulocytosis.

Diclofenac is associated with a low, but significant, incidence of hepatotoxicity and bone marrow toxicity. It has been suggested that this could be due to a reactive acyl glucuronide. An alternative hypothesis is that an oxidative reactive metabolite could be responsible for such reactions and such metabolites formed by the enzymes present in neutrophils could be responsible for bone marrow toxicity. Others had reported the formation of 2,2'-dihydroxyazobenzene during the oxidation of diclofenac by myeloperoxidase/hydrogen peroxide. In contrast, in similar experiments we did not find evidence for the formation of 2,2'-dihydroxyazobenzene, but we did find several products, including a reactive iminoquinone. The same iminoquinone was formed by the oxidation of 5-hydroxydiclofenac. This iminoquinone was also formed by oxidation of diclofenac by HOCl or by activated neutrophils. It reacted with glutathione to form a conjugate. 5-Hydroxydiclofenac is also a major hepatic metabolite of diclofenac, and we found that rat hepatic microsomes oxidized 5-hydroxydiclofenac to the iminoquinone which was trapped with glutathione. This reactive metabolite represents another possible cause of the idiosyncratic reactions associated with the use of diclofenac.

In previous studies we had shown that procainamide is metabolized to reactive metabolites by activated leukocytes, and evidence pointed to involvement of myeloperoxidase (MPO). In this study we examine the metabolism of procainamide by MPO/H2O2, in the presence and absence of chloride ion. In the absence of chloride ion, the metabolism was very similar to that seen with activated leukocytes. The major metabolite was formed by oxidation of the arylamine group to a hydroxylamine. In the presence of chloride ion, a much greater degree of metabolism occurred, and the major product (40% of the starting procainamide) was a reactive species that could not be isolated. This metabolite spontaneously rearranged to 3-chloroprocainamide, and from its mass spectrum and chemical reactions, we deduce its structure to be N-chloroprocainamide. The N-chloroprocainamide metabolite reacted very rapidly with reducing agents, such as ascorbate, and also reacted with protein such as albumin, the major product in both cases being procainamide. This metabolite also chlorinated phenylbutazone. When radiolabeled procainamide was oxidized by MPO/H2O2 in the presence of albumin, covalent binding of the radiolabel to albumin occurred, and binding was greater under conditions in which N-chloroprocainamide was formed. It is probable that the failure to observe N-chloroprocainamide, when procainamide is oxidized by activated leukocytes, is due to its rapid reaction with the cells. We propose that modification of neutrophils (or neutrophil precursors in the bone marrow) by these reactive metabolites is responsible for procainamide-induced agranulocytosis. In a similar manner, procainamide-induced lupus could be due to modification of monocytes by monocyte-generated reactive metabolites.

Several types of phenytoin toxicity appear to involve leukocytes. We had previously demonstrated that other drugs were metabolized to reactive metabolites by activated neutrophils and monocytes or the combination of myeloperoxidase (MPO) and hydrogen peroxide. In this study we found that phenytoin was chlorinated by MPO/H2O2/Cl- to N,N'-dichlorophenytoin which is chemically reactive. Failure to demonstrate that activated neutrophils also formed N,N'-dichlorophenytoin appeared to be due to the rapid reaction of N,N'-dichlorophenytoin with neutrophils. We were able to demonstrate that phenytoin covalently bound to albumin in the presence of MPO/H2O2/Cl- and to neutrophils, but only if the cells were activated. Such activation leads to the release of MPO and the generation of H2O2. We, therefore, speculate that the toxicity of phenytoin may be due to the formation of N,N'-dichlorophenytoin by activated neutrophils or monocytes.

The chronic use of procainamide is associated with a high incidence of drug-induced lupus and also agranulocytosis. We have previously demonstrated that procainamide is metabolized in the liver to reactive hydroxylamine (PAHA) and nitroso (nitroso-PA) metabolites which covalently bind to protein and are toxic to lymphocytes. We proposed that these metabolites were responsible for the toxicities of procainamide. However, PAHA and nitroso-PA do not appear to escape the liver in significant concentrations. In this paper we describe the metabolism of procainamide to a reactive hydroxylamine by neutrophils and mononuclear leukocytes. Such metabolism only occurs if the cells have been stimulated to have a respiratory burst. These observations have obvious possible implications for the mechanism of procainamide-induced agranulocytosis (formation of a reactive metabolite by neutrophils) and procainamide-induced lupus (formation of a reactive metabolite by monocytes). The metabolism of drugs to reactive metabolites by monocytes may be a general mechanism for hypersensitivity reactions because monocytes play a key role in the processing of antigen and stimulation of antibody synthesis.