Lipophilic salts as membrane additives and their influence on the properties of macro- and micro-electrodes based on neutral carriers

The influence of salts containing lipophilic cations and anions on the electrical resistance of the membranes of calcium ion-selective macro- and micro-electrodes based on a neutral carrier is described. The resistance of macroelectrodes was decreased by a factor of about 50 or of about 3 compared to membranes without and with potassium tetrakis- (p-chlorophenyl)borate, respectively. No significant reduction of the membrane resistance was achieved for microelectrodes. The lower detection limit and the Ca²⁺/K⁺ selectivity factor were improved for both types of electrode.     

Indonesian propolis: chemical composition, biological activity and botanical origin

From a biologically active extract of Indonesian propolis from East Java, 11 compounds were isolated and identified: four alk(en)ylresorcinols (obtained as an inseparable mixture) (1-4) were isolated for the first time from propolis, along with four prenylflavanones (6-9) and three cycloartane-type triterpenes (5, 10 and 11). The structures of the components were elucidated based on their spectral properties. All prenylflavanones demonstrated significant radical scavenging activity against diphenylpicrylhydrazyl radicals, and compound 6 showed significant antibacterial activity against Staphylococcus aureus. For the first time Macaranga tanarius L. and Mangifera indica L. are shown as plant sources of Indonesian propolis.     

Thienopyrimidines: synthesis, properties, and biological activity

Data on the methods for the synthesis of isomeric thienopyrimidine derivatives, their chemical transformations, and biological activities are systematized and analyzed. Emphasis is given to studies published over the last 10—15 years.     

Thienopyridines: synthesis, properties, and biological activity

The current state and prospects of development of the chemistry of isomeric thienopyridines (synthesis, chemical transformations, and biological activities) are analyzed. Particular attention is given to studies published in the last 10–15 years. Dedicated to Academician V. I. Minkin on the occasion of his 70th birthday. __________ Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 4, pp. 847–885, April, 2005.     

Effect of submicellar concentrations of conjugated and unconjugated bile salts on the lipid bilayer membrane

The interaction of submicellar concentrations of various physiologically important unconjugated [sodium deoxycholate (NaDC), sodium cholate (NaC)] and conjugated [sodium glycodeoxycholate (NaGDC), sodium glycocholate (NaGC), sodium taurodeoxycholate (NaTDC), sodium taurocholate (NaTC)] bile salts with dipalmitoylphosphatidylcholine (DPPC) and dimyristoylphosphatidylcholine (DMPC) small unilamellar vesicles in solid gel (SG) and liquid crystalline (LC) phases was investigated using the excited-state prototropism of 1-naphthol. Steady-state and time-resolved fluorescence of the two excited-state prototropic forms of 1-naphthol indicate that submicellar bile salt concentration induces hydration of the lipid bilayer membrane into the core region. This hydration effect is a general phenomenon of the bile salts studied. The bilayer hydration efficiency of the bile salt follows the order NaDC > NaC > NaGDC > NaTDC > NaGC > NaTC for both DPPC and DMPC vesicles in their SG and LC phases.     

Poly(ether ester amide) microspheres for protein delivery: influence of copolymer composition on technological and biological properties

The production of PEEA microspheres with potential as carriers for protein oral delivery is described. PEEAs with different hydrophilicity were synthesized and characterized. Experiments showed that an increase in copolymer hydrophilicity gave particles less prone to cell interaction. BSA release profiles from PEEA microspheres demonstrated that an increase in polymer hydrophilicity was useful in limiting protein burst and modulating drug delivery rate by increasing PEEA degradability. These results show that fine-tuning of the hydrophilic/hydrophobic properties of PCL is essential for the formulation protein-loaded microspheres with specific properties.     

Physico-chemical behavior of bile salts

Roles and potential roles of bile salts in the human body and in health have been reviewed. The nomenclature of these biological amphiphiles, the mechanism of their formation in the liver and subsequent structural modifications in the enterohepatic cycle have been summarized. Emphasis has been placed on the controversies surrounding their physico-chemical properties, especially the patterns of their aggregation, and their ability to catalyze hydrolysis pathways in aqueous solution and to stimulate the activity of human milk lipase. The role of bile salts as biological surfactants and their participation in the dissolution of cholesterol gallstones, lipid solubilizatlon and absorption, and their ability to cause lysis of membrane surfaces has been discussed. Where possible, emphasis has been placed on the importance of the presence of monomers or small oligomers on the physico-chemical properties of these steroidal molecules.     

Crystal structures of bile salts: Sodium taurocholate

Crystals of sodium taurocholate (NaC₂₆H₄₄NO₇S · 2.5 H₂O) belonging to the triclinic space groupP1 have unit cell parametersa = 12.731 (2),b = 16.104 (2),c = 7.628 (1) A, =83.40 (1), = 101.20 (1), = 105.35 (1)°, and two molecules in the asymmetric unit. The refinement, carried out on 4424 observed reflections, gaveR = 0.059 andR _w = 0.066. The packing is characterized by bilayers, formed by antiparallel monolayers and with nonpolar outermost surfaces, held together by van der Waals interactions. Inside the bilayers there are channels, lined with polar groups, and filled by sodium ions and water molecules. A structural unit has been identified that could provide a reasonable model for the micellar aggregates of this bile salt. Supplementary Data relevant to this article have been deposited with the British Library under the reference number SUP 82125 (38 pages).     

Versatile approach to naphthoquinone phosphonium salts and evaluation of their biological activity

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Study of biologically relevant physical-chemical properties of bile salts by reverse-phase liquid chromatography

Summary The study of chromatographic behaviour of bile salts with reverse-phase HPLC columns (C18 and C8) and buffered water — methanol eluent systems indicated that the octanol-water partition coefficient and the micellar cholesterol-solubilizing capacity are linearly correlated with the chromatographic mobilities if eluents with pH>7 and 0.154 M saline concentration are used (correlation coefficients 0.98 and 0.86 respectively). The critical micellar concentration was poorly correlated with the chromatographic mobility under the various conditions tested. The pKa values of bile salts were determined by the changes of mobility with the pH of eluent. Values in the range 4.92–5.06 and 4.27–4.47 were found respectively for unconjugated and glycineconjugated bile salt, in agreement with previous estimates. Values in the range 0.74–1.02 represent the first direct evaluation for taurine-conjugates.     

Benzofuroxans: their synthesis,properties, and biological activity

The review provides a brief historical background for the establishment of structure of benzofuroxanes. Methods for their synthesis are summarized, and the chemical properties are described, which are splitted into two parts: reactions proceeding with a ring opening of the heterocycle, and those occuring with a participation of the isocyclic moiety. The biological activity of various representatives belonging to the benzofuroxan series is covered in details.

     

Chemical composition and biological activity of Salvia verbenaca essential oil

Salvia verbenaca L. (syn. S. minore) is a perennial herb known in the traditional medicine of Sicily as "spaccapetri" and is used to resolve cases of kidney stones, chewing the fresh leaves or in decoction. The chemical composition of the essential oil obtained from aerial parts of S. verbenaca collected in Piano Battaglia (Sicily) on July 2009, was analyzed by GC and GC-MS. The oil was strongly characterized by fatty acids (39.5%) and carbonylic compounds (21.2%), with hexadecanoic acid (23.1%), (Z)-9-octadecenoic acid (11.1%) and benzaldehyde (7.3%) as the main constituents. The in vitro activity of the essential oil against some microorganisms in comparison with chloramphenicol by the broth dilution method was determined. The oil exhibited a good activity as inhibitor of growth of Gram + bacteria.     

Interfacial characterization of beta-lactoglobulin networks: displacement by bile salts

The competitive displacement of a model protein (beta-lactoglobulin) by bile salts from air-water and oil-water interfaces is investigated in vitro under model duodenal digestion conditions. The aim is to understand this process so that interfaces can be designed to control lipid digestion thus improving the nutritional impact of foods. Duodenal digestion has been simulated using a simplified biological system and the protein displacement process monitored by interfacial measurements and atomic force microscopy (AFM). First, the properties of beta-lactoglobulin adsorbed layers at the air-water and the olive oil-water interfaces were analyzed by interfacial tension techniques under physiological conditions (pH 7, 0.15 M NaCl, 10 mM CaCl2, 37 degrees C). The protein film had a lower dilatational modulus (hence formed a weaker network) at the olive oil-water interface compared to the air-water interface. Addition of bile salt (BS) severely decreased the dilatational modulus of the adsorbed beta-lactoglobulin film at both the air-water and olive oil-water interfaces. The data suggest that the bile salts penetrate into, weaken, and break up the interfacial beta-lactoglobulin networks. AFM images of the displacement of spread beta-lactoglobulin at the air-water and the olive oil-water interfaces suggest that displacement occurs via an orogenic mechanism and that the bile salts can almost completely displace the intact protein network under duodenal conditions. Although the bile salts are ionic, the ionic strength is sufficiently high to screen the charge allowing surfactant domain nucleation and growth to occur resulting in displacement. The morphology of the protein networks during displacement is different from those found when conventional surfactants were used, suggesting that the molecular structure of the surfactant is important for the displacement process. The studies also suggest that the nature of the oil phase is important in controlling protein unfolding and interaction at the interface. This in turn affects the strength of the protein network and the ability to resist displacement by surfactants.     

Dimerization: First step for micelle preorganization of bile salts

The dimerization constants of sodium cholate, sodium deoxycholate and sodium chenodeoxycholate have been determined in dilute alkaline aqueous solution. The high stabilities of the dimers cannot be explained by single hydrogen bonds but multiple interactions must be involved simultaneously.     

The role of bile salts in digestion

Bile salts (BS) are bio-surfactants present in the gastrointestinal tract (GIT) that play a crucial role in the digestion and absorption of nutrients. The importance of BS for controlled release and transport of lipid soluble nutrients and drugs has recently stimulated scientific interest in these physiological compounds. BS are so-called facial amphiphiles showing a molecular structure that is very distinct from classical surfactants. This peculiar molecular structure facilitates the formation of dynamic aggregates able to solubilise and transport lipid soluble compounds. The detergent nature of BS has been studied in the literature, mostly concentrating on the self-assembly behaviour of BS in solution but also in relation to protein denaturation and its effect on improving proteolysis. In contrast, the affinity of BS for hydrophobic phases has received less attention and studies dealing directly with the interfacial behaviour of BS are very limited in the literature. This is despite the fact that the interfacial activity of BS plays a vital role in fat digestion since it is closely involved with lypolisis. BS adsorb onto fat droplets and can remove other materials such as proteins, emulsifiers and lipolysis products from the lipid surface. The unusual surface behaviour of BS is directly related to their intriguing molecular structure and further knowledge could provide an improved understanding of lipid digestion. This review aims to combine the new insights gained into the surface properties of BS and their role in digestion. A better understanding of surface activity of BS would allow manipulation of physico-chemical and interfacial properties to modulate lipid digestion, improve bioavailability of lipid soluble nutrients and reduce absorption of saturated fats, cholesterol and trans fats.     

Interactions of phenothiazine drugs with bile salts: Micellization and binding studies

An evaluation of the interactions of phenothiazine tranquilizer drugs (promazine hydrochloride; PMZ and promethazine hydrochloride; PMT) with bile salts viz., sodium cholate (NaC) and sodium deoxycholate (NaDC) in aqueous medium, investigated through different physicochemical measurements is presented in this work. The mixed micellization behavior and surface properties of the phenothiazine-bile salt systems have been analyzed by conductivity and surface tension measurements. Application of different theoretical approaches to all the phenothiazine-bile salt mixtures shows a non-ideal behavior. Further, the spectroscopic techniques such as UV-visible and steady state fluorescence have been employed to study the binding of phenothiazines with bile salts. The stoichiometric ratios, binding constants (K), and free energy change (ΔG) for the phenothiazine-bile salt complexes were estimated from the Benesi-Hildebrand (B-H) double reciprocal plots obtained by using the changes in spectral intensities of phenothiazines on addition of bile salts. The results are discussed in the light of use of bile salts as promising drug delivery agents for phenothiazines and hence improve their bioavailabilty.     

Synthesis and biological activity of quaternary phosphonium salts based on 3-hydroxypyridine and 4-deoxypyridoxine

Methods for the synthesis of quaternary phosphonium salts based on 3-hydroxypyridine and 4-deoxypyridoxine were developed. Some of obtained compounds possess high antibacterial and antitumor activity in vitro.     

Study of the interaction between oxygen and bile salts

The interaction between molecular oxygen and bile salts, previously observed using chemiluminescence techniques, is studied in this paper by electrochemical techniques to further highlight the nature of the interaction. A shift of half-wave potential of the first polarographic wave for the reduction of molecular oxygen was observed in solutions in the presence of bile salts. The shift could be related to different phenomena, such as adsorption of bile salt molecules on the mercury electrode, irreversibility of the oxygen reduction reaction, pH of the solution. Experimental results suggest the exclusion of the above mentioned processes and outline the occurrence of a direct interaction between oxygen and bile salts, where the hydrophobic face of bile salt monomers and/or small aggregates are involved, enhancing so dismutation of superoxide ion produced at the electrode. The presence of bile salts in solutions containing triphenylphosphine oxide, a hydrophobic surfactant, increases also the wave of reduction of molecular oxygen. As a consequence bile salts, beside the well-assessed physiological roles, can behave as oxygen carrier and as antioxidant, preventing the oxidation of biological compounds by superoxide ion.