生物表面活性剂胆汁盐胶束化及相行为

生物表面活性剂胆汁盐类以其在生物体内重要的生理功能及不同于传统表面活性剂独特的结构特点在众多领域引起了广泛的关注。本文对国内外关于胆汁盐类表面活性剂的胶束结构、表面吸附行为及胆汁盐在水溶液中的聚集体行为的研究成果进行了综述。同时,对胆汁盐与传统表面活性剂、双尾表面活性剂及天然脂类表面活性剂的相互作用以及聚集体的形成、胆汁盐诱导聚集体结构转变等方面的研究成果也进行了综述。     

Optimization of solid-phase extraction and solid-phase microextraction for the determination of alpha- and beta-endosulfan in water by gas chromatography-electron-capture detection

The electrophoretic behaviour of ionizable and neutral alkylxanthines commonly used in pharmaceutical preparations was studied. The performance of various separation modes including capillary zone electrophoresis (CZE), cyclodextrin electrokinetic chromatography, and micellar electrokinetic chromatography (MEKC) with either sodium dodecyl sulfate (SDS) or bile salts as surfactants, was assessed. CZE in an alkaline medium successfully separates ionizable xanthines and dyphylline. The addition of carboxymethyl-β-cyclodextrin to the background electrolyte allows only partial resolution of neutral xanthines. Based on MEKC results, bile salts exhibit more discrimination ability than SDS to separate similar xanthines. The best results are provided by taurodeoxycholic acid, which ensures baseline separation of xanthines.     

Effects of pharmaceutical excipients on cloud points of amphiphilic drugs

The clouding behavior, i.e., formation of phase separation at elevated temperature (the temperature being known as cloud point (CP)), of three amphiphilic drugs, amitriptyline (AMT), clomipramine (CLP) and imipramine (IMP) hydrochlorides in the presence of various additives, like cationic surfactants (conventional and gemini), nonionic surfactants, bile salts, anionic hydrotropes, sodium salts of fatty acids and cyclodextrin has been investigated. These additives are generally used as drug delivery systems. The drugs used are tricyclic antidepressants. All the surfactants increase the CP of mixed micelles formed by cationic (conventional and gemini) and nonionic surfactants. Hydrotropes, bile salts and fatty acid salts, when added in low concentrations, increase the CP, whereas at high concentrations, they decrease it. β-Cyclodextrin behaves as simple sugar and decreases the CP of the drug solutions.     

Bile Salts in Chiral Micellar Electrokinetic Chromatography: 2000–2020

Bile salts are naturally occurring chiral surfactants that are able to solubilize hydrophobic compounds. Because of this ability, bile salts were exploited as chiral selectors added to the background solution (BGS) in the chiral micellar electrokinetic chromatography (MEKC) of various small molecules. In this review, we aimed to examine the developments in research on chiral MEKC using bile salts as chiral selectors over the past 20 years. The review begins with a discussion of the aggregation of bile salts in chiral recognition and separation, followed by the use of single bile salts and bile salts with other chiral selectors (i.e., cyclodextrins, proteins and single-stranded DNA aptamers). Advanced techniques such as partial-filling MEKC, stacking and single-drop microextraction were considered. Potential applications to real samples, including enantiomeric impurity analysis, were also discussed.     

胆酸盐参与的自组装及微纳米材料制备

胆酸盐类物质可看作是一类阴离子型甾族生物表面活性剂,鉴于其特殊的两亲性骨架结构、独特的物理化学性质及其良好的生物相容性和环境友好性,其在溶液中能够参与超分子自组装形成有序聚集结构,且可以作为模板在微纳材料制备领域有着重要应用。本文结合我们课题组的研究工作,综述了近期国内外相关研究,详细介绍了生物小分子氨基酸对胆酸盐聚集行为的影响、胆酸盐参与形成的超分子凝胶及胆酸盐参与构筑的微纳米材料制备等方面的研究进展,以期对胆酸盐参与的自组装及微纳米材料制备领域的研究有更全面更深入的了解,为后续的应用研究提供坚实的基础。     

Interfacial & colloidal aspects of lipid digestion

Amongst the main issues challenging the food manufacturing sector, health and nutrition are becoming increasingly important. Global concerns such as obesity, the ageing population and food security will have to be addressed. Food security is not just about assuring food supply, but is also about optimising nutritional delivery from the food that is available [1]. Therefore one challenge is to optimise the health benefits from the lipids and lipid soluble nutrients.Colloid scientists have an affinity for lipids because they are water insoluble, however this presents a challenge to the digestive system, which has to convert them to structures that are less insoluble so they are available for uptake. Despite this, the human digestive system is remarkably effective at digesting and absorbing most lipids. This is primarily driven through maximising energy intake, as lipids possess the highest calorific value, which was a survival trait to survive times of famine, but is now an underlying cause of obesity in developed countries with high food availability.The critical region here is the lipid-water interface, where the key reactions take place to solubilise lipids and lipid soluble nutrients. Digestive lipases have to adsorb to the oil water interface in order to hydrolyse triacylglycerols into fatty acids and mono glycerides, which accumulate at the interface [2], and inhibit lipase activity. Pancreatic lipase, which is responsible for the majority of lipid hydrolysis, also requires the action of bile salts and colipase to function effectively. Bile salts both aid the adsorption of co-lipase and lipase, and help solubilise the lipolysis products which have accumulated at the interface, into mixed micelles composing bile salts and a range of other lipids, to facilitate transport to the gut mucosal surface prior to uptake and absorption.The process can be affected by the lipid type, as shorter chain, fatty acids are more easily absorbed, whereas the uptake of longer chain fatty acids, particularly the very long chain n-3 fatty acids from fish oils are dependent on source and so may depend on food microstructure for optimal uptake [3]. The uptake of some poorly water soluble nutrients are enhanced by the presence of lipids, but the mechanisms are not clear. In addition, controlling the digestion of lipids can be beneficial as slower release of lipids into the bloodstream can reduce risk of cardiovascular disease, and can promote gut feedback processes that reduce appetite.This presents an opportunity to colloid and interfacial science, as there are many unanswered questions regarding the specific physicochemical mechanisms underlying the process of lipid digestion and uptake. I will review our current knowledge of lipid digestion and present examples of how fundamental research in colloidal and interface science is beginning to address these issues. These include the adsorption behaviour of physiological surfactants such as bile salts; interfacial processes by which different polar lipids can influence lipolysis; and the effect of emulsion based delivery systems on cellular uptake of lipid soluble nutrients.A fundamental understanding of these processes is required if we are to develop intelligent design strategies for foods that will deliver optimal nutrition and improved health benefits in order to address the global challenges facing the food sector in the future.     

Estimation of critical micelle concentrations of bile acids by reversed-phase high performance liquid chromatography

The critical micelle concentration (CMC) for bile salts or other surfactants is defined as that solute concentration at which appreciable changes in such phenomena as light scattering, surface tension, or solubilization of other organic molecules occur, these changes indicating appearance of surfactant aggregates. The CMC thus reflects hydrophobic interactions of the surfactant with itself. The self-association of hydrophobic molecules resembles the partition of a solute into the lipophilic phase in reversed-phase high performance liquid chromatography (RPLC): Both processes can be considered as transfers of a molecule from an aqueous to a lipophilic medium. The critical micelle concentration of a particular bile salt, being a measure of its hydrophobic self-association, should therefore be correlated with its Chromatographic mobility since they are fundamentally related phenomena. Experimentally, significant correlations between these quantities are obtained, both for bile salts andn-alky1 sulfonates, and only microgram amounts of sample are required for RPLC measurements. Among three homologous series of bile salt surfactants, CMC values predicted from RPLC measurements agree, within a standard error of 7%, with CMC values determined directly. This suggests the applicability of reversed-phase liquid chromatography to the micro-scale determination of critical micelle concentrations of bile salts,n-alkyl sulfonates, and other homologous series of surfactants.This work was supported in Part by NIH Grants HL-07878 (W.H.E.) and AI-21873 (B.G.B.) and by a Fulbright Senior Fellowship (B.G.B.). This is paper LXXX in the series Bile Acids by W.H.E.Deceased March 29, 1986     

Fluorescence turn on by cholate aggregates

Bile salts, including sodium cholate (NaCh), are amphiphilic molecules with a concave hydrophilic side and a convex hydrophobic side. By forming aggregates in aqueous solution, these natural surfactants fulfill vital biological roles in the solubilization of cholesterol, lipids, and fat-soluble vitamins and thus are involved in the transport and absorption of important biological molecules. Following our success with the encapsulation of fluorescent protein chromophore (FP) analogs by synthetic hydrophobic and hydrophilic hosts, based upon substitution patterns, we now report the binding and turn on of other analogs by bile salt aggregates, observations which may lead to new tools for studying trafficking in these important systems.     

Computer Simulations of the Formation of Bile Salt Micelles and Bile Salt/DPPC Mixed Micelles in Aqueous Solutions

Brownian dynamics simulations for a coarse-grained model have been performed to study the formation of micelles from bile salts and mixed micelles with dipalmitoyl-phosphatidylcholine (DPPC) in aqueous solutions. The particular association behavior of bile salts as facial surfactants was shown to be caused by their special molecular architecture with a hydrophilic and a hydrophobic side. The experimentally observed smooth transition into the micellar region with increasing concentration is reproduced. Micelle size distributions have been evaluated at different bile salt concentrations. Typical structures of pure bile salt micelles could be identified. The composition and the structure of mixed micelles have been studied in their dependence on the bile salt/lipid concentration ratio in the aqueous solution. We have found that the bile salt fraction in the mixed micelles increases considerably with increasing bile salt/lipid concentration ratio and decreasing micelle size. The structural and thermodynamic features of micelle formation in the aqueous bile salt solutions with DPPC, which we have studied with the coarse-grained model, are in good qualitative agreement with experimental findings.     

胶束电动毛细管色谱法分析手性化合物

对近年来胶束电动毛细管色谱法（ＭＥＣＣ）分析手性化合物方面的工作进行了评述,简述了ＭＥＣＣ分离手性化合物的原理,并探讨了几种ＭＥＣＣ手性分离体系的分离机理。     

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.     

Adsorption of polar lipids at the water-oil interface

Dietary fat has long been recognized as an essential component in nutrition. However, most of the lipids present in food need to be converted into more bioavailable compounds. Lipases have a crucial role in converting triglycerides into more polar lipids with increased water solubility and a tendency to form micelles. However, the surface active molecules generated by lipolysis may have a detrimental effect on the interfacial biocatalysis. In the present work we evaluate the interfacial properties of lipase-generated molecules during fat digestion. By using the pendant drop technique we assessed the amphiphilic character of fatty acid salts, monoglycerides, and diglycerides as individual surfactants and mixtures. The experimental results are fitted with a mathematical model, which assists in the determination of the interfacial properties of the surfactants. Our results show that monoglycerides have considerably higher interfacial activity than fatty acid salts and diglycerides. Therefore, the interface will soon be dominated by monoglycerides. The pH dependency of the interfacial activity of fatty acids is also explored in the current work. We believe that our results can contribute to a better understanding of the complex interfacial phenomena occurring during fat digestion.     

A potentiometric titration study on the dissociation of bile acids related to the mode of interaction between different head groups of nonionic surfactants with free bile salts upon mixed micelle formation in water

By constructing an elaborate set of potentiometric titration together with data analysis system, apparent acid dissociation indices (pK _a ^app ) for two bile acids were determined in the mixed surfactant system of bile salts (Sodium Deoxycholate, NaDC, and Sodium Chenodeoxycholate, NaCDC) with nonionic surfactants (Hexaethyleneglycol monon-dodecylether, C₁₂E₆, Decanoyl-N-methylglucamide, MEGA-10) in aqueous solution at ionic strength 1.5 as a function of mole fraction in the surfactant mixture. It was found that with increasing the bile salt concentration, pK _a ^app as well as pH showed an abrupt rise at a certain concentration of the bile salt being regardable as a critical micellization concentration (CMC) and reached a constant value at the range sufficiently higher than CMC for each pure bile salt system, meaning that the dissociation degree of carboxyl group in micelle is smaller than that in bulk. In the mixed systems of free bile salts with nonionic surfactants, the dissociation state of carboxyl groups in mixed micelles depends on the species of hydrophilic group of nonionic surfactants as well as on mole fraction in the surfactant mixture.     

Role of adsorbed surfactant in the reaction of aryl diazonium salts with single-walled carbon nanotubes

Because covalent chemistry can diminish the optical and electronic properties of single-walled carbon nanotubes (SWCNTs), there is significant interest in developing methods of controllably functionalizing the nanotube sidewall. To date, most attempts at obtaining such control have focused on reaction stoichiometry or strength of oxidative treatment. Here, we examine the role of surfactants in the chemical modification of single-walled carbon nanotubes with aryl diazonium salts. The adsorbed surfactant layer is shown to affect the diazonium derivatization of carbon nanotubes in several ways, including electrostatic attraction or repulsion, steric exclusion, and direct chemical modification of the diazonium reactant. Electrostatic effects are most pronounced in the cases of anionic sodium dodecyl sulfate and cationic cetyltrimethylammonium bromide, where differences in surfactant charge can significantly affect the ability of the diazonium ion to access the SWCNT surface. For bile salt surfactants, with the exception of sodium cholate, we find that the surfactant wraps tightly enough such that exclusion effects are dominant. Here, sodium taurocholate exhibits almost no reactivity under the explored reaction conditions, while for sodium deoxycholate and sodium taurodeoxycholate, we show that the greatest extent of reaction is observed among a small population of nanotube species, with diameters between 0.88 and 0.92 nm. The anomalous reaction of nanotubes in this diameter range seems to imply that the surfactant is less effective at coating these species, resulting in a reduced surface coverage on the nanotube. Contrary to the other bile salts studied, sodium cholate enables high selectivity toward metallic species and small band gap semiconductors, which is attributed to surfactant-diazonium coupling to form highly reactive diazoesters. Further, it is found that the rigidity of anionic surfactants can significantly influence the ability of the surfactant layer to stabilize the diazonium ion near the nanotube surface. Such Coulombic and surfactant packing effects offer promise toward employing surfactants to controllably functionalize carbon nanotubes.     

表面活性剂作为电解液添加剂在毛细管电泳中的应用

本综述归纳了近年来毛细管电动色谱的理论研究，以及阴离子、阳离子和非离子表面活性剂的应用研究工作，并介绍了毛细管电动色谱的改良新技术，如环糊精、胆汁盐，其它旋光异构体选择及有机溶剂等作为添加剂的应用，引用文献１７４篇。     

Separation of bisphenol A and three alkylphenols by micellar electrokinetic chromatography

Analytical conditions of pH, surfactants, and additives were investigated for the simultaneous separation of bisphenol A and alkylphenols by micellar electrokinetic chromatography. Reproducibility of migration time was improved at higher pH (pH 8.0). When five surfactants having linear alkyl chains or four bile salts were used, the separation of hydrophobic phenols and 4-nonylphenol isomers was not achieved. In order to improve the separation, the use of additives with sodium dodecyl sulfate solution was investigated. The separation of hydrophobic phenols was improved by the addition of organic solvents, however, isomers were not separated. Their separation was achieved by the addition of beta- or gamma-cyclodextrin.     

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.     

Molecular simulation of biosurfactants with relevance to food systems

The application of molecular modelling, and in particular all-atom and coarse grained molecular dynamics simulation, to the study of low molecular weight surfactants with relevance to food systems is reviewed. Two key aspects of surfactant behaviour — their ability to form micelles and their tendency to adsorb to fluid–fluid interfaces (air–water and oil–water) are covered. Since the modelling literature on synthetic amphiphilic surfactants is vast, and much of it not directly relevant to foods, the review concentrates on biosurfactants. Two particular topics are covered in detail: the behaviour of bile salts because of the importance of these in understanding food digestion; the behaviour of novel glycolipid and lipopeptide surfactants derived from microorganisms (bacteria and yeast) due to their increasing importance as functional ingredients in consumer products including foods.     

New pressure‐assisted sweeping on‐line preconcentration for highly polar environmentally relevant nitrosamines: Part 2. Cationic and anionic surfactants with zero‐flow capillaries

We recently introduced a pressure‐assisted sweeping‐reversed migration‐EKC (RM‐EKC) method for preconcentration of neutral polar N‐nitrosamines with low affinity for the micellar phase. The type of surfactant and phase ratio are dominant factors in dictating the magnitude of interactions between analyte and micellar phase, thus four surfactants (anionic and cationic) with a range of functionalities (SDS, ammonium perfluorooctanoate (APFO), bile salts, and cetyltrimethylammonium chloride (CTAC)) were evaluated for sweeping‐RM‐EKC of highly polar N‐nitrosamines. All gave acceptable results for sweeping‐RM‐EKC when used in high concentrations (≥200 mM) with low EOF. While no single surfactant was superior by all measures, all but the bile salts had useful performance characteristics. APFO showed the narrowest peak widths and highest number of theoretical plates, though two species co‐migrated at all concentrations (25–300 mM); SDS and the cationic surfactant CTAC also showed good separation characteristics and could resolve all peaks, but CTAC had wider separation window. Various types of capillaries coated for EOF control were compared for use with anionic and cationic surfactants. A commercial zero‐EOF capillary coated with a polymer bearing sulfonic acid functional groups showed superior EOF suppression and reproducibility of migration time with all surfactants.     

A study of the adsorption of bile salts onto model lecithin membranes

Bile salts play a central role in the promotion of cytotoxicity or cytoprotection. In this study, we examined the interaction of different bile salts with egg lecithin vesicles using 31P NMR spectroscopy. The effects of taurochenodeoxycholate (TCDC or 3alpha,7alpha,-dihydroxy-5beta-cholanoyl taurine, of tauroursodeoxycholate (TUDC) or 3alpha,7beta,-dihydroxy-5beta-cholanoyl taurine) and of taurobetamuricholate (TbetaMC or 3alpha,6beta,7beta,-trihydroxy-5beta-cholanoyl taurine), at various bile salt/lecithin ratios, were evaluated. From the percent 31P present in vesicles, the micellar capacity of bile salts to dissolve lecithin was determined. TCDC was incorporated into vesicles for bile salt/lecithin molar ratios lower than 0.62 while for TUDC and TbetaMC, the critical ratios were 0.94 and 1.1, respectively. The 31P chemical shift change was markedly larger with TCDC than that found with TUDC and TbetaMC. In order to specify the low interactions observed between hydrophilic bile salts and lecithin, we determined the intermixed micellar/vesicular bile salt concentrations (IMVC) of bile salt/lecithin solutions using rapid ultrafiltration-centrifugation for TUDC and lecithin solubility measurements for TUDC, TbetaMC and TCDC. The low IMVC obtained indicate that even hydrophilic bile salts were bound mostly to the mixed aggregates. In conclusion, the low disturbance in the arrangement of lecithin induced by TUDC and TbetaMC appears to be due to the interfacial location of these bile salts. TCDC (7alpha OH) penetrates more deeply in the membrane than the 7beta hydroxylated bile salts that may partly explain the distinct damaging effects of these bile salts.