Cleavable Surfactants Research Articles

Nonionic, Cleavable Surfactant for Top-Down Proteomics.

Nonionic surfactants are often used as general reagents for cell lysis enabling protein extraction, stabilization, and purification under nondenaturing conditions for downstream analysis in structural biology. However, the presence of surfactants in the sample matrix often has a deleterious effect on electrospray ionization (ESI)-mass spectrometry (MS) analysis of proteins and complexes. Here, we report a nonionic, cleavable surfactant, n-decyl-disulfide-β-D-maltoside (DSSM), for top-down proteomics. DSSM was designed to mimic the properties of one of the most common surfactants used in structural biology, n-dodecyl-β-D-maltoside (DDM), but contains a disulfide bond that allows for facile cleavage and surfactant removal before or during MS analysis. We have shown that DSSM is compatible with direct electrospray ionization (ESI)-MS analysis and reversed-phase liquid chromatography (RPLC)-MS analysis of proteins and protein complexes. We have demonstrated that DSSM can facilitate top-down proteomic characterization of membrane proteins such as a model ion channel protein and a G protein-coupled receptor as well as endogenous proteins from cell lysates for the determination of sequence variations and posttranslational modifications (PTMs). Conceivably, DSSM could serve as a general replacement for DDM in proteomic experiments and structural biology studies.

Tailoring liquid crystals as vehicles for encapsulation and enzyme-triggered release.

Nanoscale assemblies of amphiphiles have been vividly explored in pharmaceutical formulations as drug nanocarriers. Aqueous interfaces of liquid crystals (LCs) are known to direct the self-assembly of a range of amphiphiles. These amphiphile-decorated interfaces of LCs have evoked interest for applications as diverse as the detection of disease markers, screening of toxins, mimicking complex biomolecular interactions, and cell-based sensing. Aiming to explore these interfaces for encapsulation and enzyme-triggered release, we report a simple and rational design of enzyme-responsive LC interfaces programmed with a cleavable non-ionic surfactant. We encapsulated a hydrophobic dye within the surfactant micelles and investigated the enzyme-triggered dye release. Interestingly, we found that LC droplets, when decorated with the dye-loaded micelles, offer significant advantages over the conventional micellar nanocarriers. The LC droplets showed controlled release features which weren't affected at high dilutions. Our work, although exploratory in nature, provides fresh approaches for tailoring LC interfaces as vehicles for drug delivery.

Design of Stimuli-Responsive Dynamic Covalent Delivery Systems for Volatile Compounds (Part 2): Fragrance-Releasing Cleavable Surfactants in Functional Perfumery Applications.

Amphiphilic imines prepared by condensation of a hydrophobic fragrance aldehyde with a hydrophilic amine derived from a poly(propylene oxide) and poly(ethylene oxide) diblock copolymer were investigated as cleavable surfactant profragrances in applications of functional perfumery. In water, the cleavable surfactants assemble into micelles that allow solubilization of perfume molecules that are not covalently attached to the surfactant. Dynamic headspace analysis on a glass surface showed that solubilized perfume molecules evaporated in a similar manner in the presence of the cleavable surfactant as compared with a non-cleavable reference surfactant. Under application conditions, the cleavable surfactant imine hydrolysed to release the covalently linked fragrance aldehyde. The profragrances were stable during storage in aqueous media, and upon dilution showed a blooming effect for the hydrolytical fragrance release and a more balanced performance of a solubilized perfume by retaining the more volatile fragrances and boosting the evaporation of the less volatile fragrances.

Synthesis and Properties of New Cleavable Cationic Surfactants Containing Carbonate Groups

AbstractA novel series of cleavable alkyltrimethylammonium surfactants with different hydrocarbon chain lengths (C8–16) were synthesized. A carbonate break site inserted between the polar head and the hydrocarbon chain makes these compounds hydrolyzable. The reagents used are renewable, (bio)degradable, or reusable. The hydrolysis of these cleavable surfactants will lead to the generation of fatty alcohols and choline, which is an essential biological nutrient. The surface activities in aqueous solution of the synthesized carbonates fulfill the requirement of being good surfactants. In addition, the cleavable compounds containing n‐decyl and n‐dodecyl chains showed similar or higher antimicrobial activities when compared to a non‐cleavable analog.

Synthesis and Properties of Cleavable Quaternary Ammonium Compounds.

Quaternary ammonium compounds are widely used as antiseptic and disinfectant. It is been a concern that their widespread use will lead to an increase of environmental problems, therefore the development of biodegradable surfactants is necessary. The present research is aimed at the design of novel amphiphilic molecules with similar properties to those already known but more biodegradable. Based on benzalkonium chloride (BAC), novel carbonate cleavable surfactants (CBAC) were synthesized. The breakable carbonate sites make CBAC compounds more degradable and potentially more biodegradable than their non-cleavable BAC analogues. Natural products such as fatty alcohols (C8-C16) and N,N-dimethyl-2-aminoethanol were used as reagents for the synthesis of CBAC8-16. These amphiphilic compounds were characterized in terms of surface properties and antimicrobial activity against Gram-positive and Gram-negative bacteria, yeasts and moulds. The novel surfactants showed similar surface activities in aqueous solutions when compared to BAC. Also, the surface activity/structure relationship revealed that carbonate cleavable surfactants with n-decyl group (CBAC10) showed the same behaviour as non-cleavable BAC. Furthermore, compounds containing n-octyl (CBAC8), n-decyl (CBAC10) and n-dodecyl (CBAC12) group showed strong antimicrobial activities.

Cationic Surfactants: Self-Assembly, Structure-Activity Correlation and Their Biological Applications.

The development of biotechnological protocols based on cationic surfactants is a modern trend focusing on the fabrication of antimicrobial and bioimaging agents, supramolecular catalysts, stabilizers of nanoparticles, and especially drug and gene nanocarriers. The main emphasis given to the design of novel ecologically friendly and biocompatible cationic surfactants makes it possible to avoid the drawbacks of nanoformulations preventing their entry to clinical trials. To solve the problem of toxicity various ways are proposed, including the use of mixed composition with nontoxic nonionic surfactants and/or hydrotropic agents, design of amphiphilic compounds bearing natural or cleavable fragments. Essential advantages of cationic surfactants are the structural diversity of their head groups allowing of chemical modification and introduction of desirable moiety to answer the green chemistry criteria. The latter can be exemplified by the design of novel families of ecological friendly cleavable surfactants, with improved biodegradability, amphiphiles with natural fragments, and geminis with low aggregation threshold. Importantly, the development of amphiphilic nanocarriers for drug delivery allows understanding the correlation between the chemical structure of surfactants, their aggregation behavior, and their functional activity. This review focuses on several aspects related to the synthesis of innovative cationic surfactants and their broad biological applications including antimicrobial activity, solubilization of hydrophobic drugs, complexation with DNA, and catalytic effect toward important biochemical reaction.

Label-free, rapid, and sensitive detection of carboxylesterase using surfactant-doped liquid crystal sensor

Carboxylesterases (CES) has been regarded as a most effective biomarker candidate of the hepatoma cells and fruitfully used in the early detection. For this reason, establishing a reliable and simple system to detect CES has become attractive in the practical applications of medical diagnosis and treatment. In this study, a novel strategy for monitoring CES based on the aqueous/liquid crystals (LCs) interface was reported. A cleavable surfactant, N-octadecyloxycarbonylmethyl-N, N, N-trimethylammonium bromide (OTB) was synthesized and utilized to control the orientation of 4-cyano-4′-pentylbiphenyl (5CB) molecules on aqueous/LCs interface. The formation of OTB self-assembly monolayer promotes the alignment of the LCs, on average, normal to the surface (homotropic), whereas a corresponding black image was observed by polarized optical microscopy (POM). Subsequently, the doping of CES induces the hydrolysis of the OTB, resulting in the disruption of OTB monolayer and thereby an obvious dark-to-bright transition in the optical response. This optical transition provides a quick and easy way of detecting CES. OTB-decorated LC surfaces have been developed as a sensor, with a detection limit of 18 U/L for CES detection. As-made LCs-based sensor exhibits superior detection sensitivity and specificity towards the detection of CES, as well as the excellent long-term stability. The preliminary results shows success in sensing CES from the urine samples, which also suggests the promising detection performance of LCs sensor in practical situations. In summary, the as-prepared CES sensor, offers several advantages along with its cost-effective and easy fabrication procedure, demonstrates its potential for medically assisted therapy in human samples.

Cleavable Surfactants: A Comparison between Ester, Amide, and Carbonate as the Weak Bond

AbstractCleavable surfactants, i.e., surfactants in which a weak bond has deliberately been inserted into the molecule, are of interest when remaining surface‐active material at a surface can cause problems. Ester and amide bonds are established as week linkages in surfactants but these generate an acid when they hydrolyze. For some applications, acidic degradation products are unwanted. Surfactants with a carbonate bond between the polar headgroup and the hydrophobic tail are of interest for such purposes. In this article, we compare the physical–chemical properties of nonionic carbonate surfactants with those of the corresponding ester and amide surfactants. The half‐lives of the different cleavable surfactants are also compared and it was found that a carbonate bond is slightly more stable to alkaline hydrolysis than an ester bond when present in otherwise identical structures. A nonionic Gemini surfactant with a carbonate bond in the spacer, which on hydrolysis decomposes into two identical single‐tailed nonionic amphiphiles, is also presented. The hydrolysis kinetics for this surfactant was studied in some detail and it was found that it degrades much faster at low temperature than at higher temperature. This anti‐Arrhenius type of hydrolysis kinetics is proposed to be due to the reverse solubility versus temperature behavior of ethoxylated surfactants.

Physiological neutral pH drives a gradual lamellar-to-reverse cubic-to-reverse hexagonal phase transition in phytantriol-based nanoparticles.

Dispersed systems of bicontinuous cubic phases, called cubosomes, show a drug release rate faster than those obtained using other liquid-crystalline phases. To minimize side effects associated with the accelerated release of incorporated drugs, compounds may be added in the dispersions to produce systems of slow initial release and then fast release only in the desired action region. This paper addresses the addition of 10.0% (w/w) of decyl betainate chloride (DBC), a cleavable surfactant, into phytantriol/Pluronic-based dispersions to generate lamellar-to-cubic-to-hexagonal phase transitions. Small-angle X-ray scattering (SAXS) was used to analyze the mesophases obtained with the addition of DBC and pH variation. Transmission electron microscopy (TEM) images confirmed the presence of niosomes after the addition of DBC. The niosomes formed in these systems are pH-responsive with lamellar-to-hexosomes transitions at pH ≥ 7.4. The system investigated herein is gastro-resistant presenting potential therapeutic role for controlled release of drugs in neutral or alkaline environments of the organism.

Ultrasensitive detection of glutathione based on liquid crystals in the presence of γ-glutamyl transpeptidase

Glutathione (GSH) is of significance in human pathology due to its many cellular functions. γ-Glutamyl transpeptidase (γ-GT) plays a key role in the balance of GSH by breaking down extracellular GSH. In this study, we proposed a novel strategy for sensitive and selective detection of GSH based on LC sensing platform coupled with its inhibition of γ-GT. The γ-GT cleavable surfactant, dodecyl N-ethanamide N, N, N-trimethylammonium bromide (DAA), was synthesized and utilized to decorate the aqueous/LC interface. A black optical image of LCs was observed due to formation of the self-assembled DAA monolayer at the interface. Subsequently, the optical response of LCs returned to bright appearance after transferring γ-GT to the DAA-laden interface because DAA could be enzymatically hydrolyzed by γ-GT and the monolayer was disrupted. Interestingly, LCs remained dark images after the DAA-decorated interface in contact with the pre-incubated GSH and γ-GT. The detection limit of GSH reached 1 pg/mL, which demonstrates high competitiveness with the current assays. The detection mechanism of GSH was explained by Isothermal titration calorimetry (ITC) measurements and Fourier transform infrared (FTIR) spectroscopy. This work presents an appealing route to achieve ultrasensitive detection of GSH according to its hydrolysis by γ-GT and the as-prepared simple and robust LC-based sensing platform has potentials in the diagnosis of GSH-related diseases (e.g. cancer, liver damage, and malignant neoplasms).

Construction of liquid crystal droplet-based sensing platform for sensitive detection of organophosphate pesticide

Alkaline phosphatase (ALP), as an essential disease biomarker, widely distributes in various tissues, and plays a significant role in diagnosis and treatment of some diseases (e.g. cancers and liver dysfunction). Dichlorvos (DDVP), as one of typical organophosphate pesticide, could be hydrolyzed by ALP. In this work, we constructed a simple but robust 4-cyano-4′-pentylbiphenyl (5CB) droplet sensing platform for sensitive and convenient detection of DDVP based on its hydrolysis by ALP. The optical responses of liquid crystals (LCs) originated from controlling orientations of 5CB by using an ALP cleavable surfactant, sodium monododecyl phosphate (SMP). A dark crossed optical image of 5CB was observed due to formation of the SMP monolayer at the aqueous/LC droplet interface. Subsequently, 5CB turned to bright fan-shaped optical appearance upon addition of ALP and SMP mixture. Interestingly, LCs remained dark crossed optical images in contact with the pre-incubated mixture of DDVP and ALP. The detection limit of DDVP reached ~0.1 ng/mL. Isothermal titration calorimetry (ITC) and humam ALP ELISA kit provided strong evidence for the detection mechanism. This strategy was also used to evaluate whether the maximum pesticide residue limits of tomatoes conform to the relevant national standard requirement or not. Our study holds promise for real-time and label-free detection of pesticides with high sensitivity by employing portable LC-based sensing platform.

A reverse degradation vs. temperature relationship for a carbonate-containing gemini surfactant

The rate of hydrolysis of cleavable surfactant is known to have a strong temperature dependence. A nonionic gemini surfactant with a readily hydrolysable carbonate bond as spacer unit has been synthesized and evaluated. A carbonate linkage is special as spacer unit in a gemini surfactant because the hydrolysis results in two identical molecules, in this case a hydroxy-substituted nonionic surfactant, along with carbon dioxide. The critical micelle concentration for the gemini surfactant was an order of magnitude lower than that of the degradation product. The degradation of the new surfactant and specifically the effect of temperature on the rate of hydrolysis was investigated in detail. It was found that alkaline hydrolysis was rapid at 15 °C but very slow at 30 °C, i.e. there was a reverse relationship between rate of hydrolysis and temperature. The same behavior was found for monomeric nonionic carbonate-containing surfactants that were synthesized and used as references. This unusual behavior, which can be of practical use, is explained by the reverse solubility vs. temperature profile for amphiphiles carrying a polyoxyethylene chain.

Solubility Enhancement of Polycyclic Aromatic Hydrocarbons by an Eco-Friendly Ester-Linked Gemini Surfactant and its Mixtures with Conventional Surfactants

AbstractThe present study deals with the solubility enhancement of the two polycyclic aromatic hydrocarbons (PAHs) anthracene and pyrene in the aqueous micellar system of the cationic ester-containing cleavable gemini surfactant ethane-1,2-diyl-bis(N,N-dimethyl-N-tetradecylammoniumacetoxy) dichloride (14-E2-14 = C14H29(CH3)2N+(CH2COOCH2)2N+(CH3)2C14H29 · 2Cl−)), and its equimolar binary mixtures with some typical conventional cationic, anionic and non-ionic surfactants. The surface tension and conductivity measurements were used to evaluate the physicochemical parameters such as the critical micelle concentration (CMC), the interaction parameter (βm) and Gibbs excess free energy of micellization (ΔGexm) of the systems. The extent of solubilization of the micellar systems towards PAHs has been quantified in terms of molar solublization ratio (MSR), micellar/water partition coefficient (ln Km) and the standard Gibbs free energy of solubilization (ΔGs0). Above the CMC, all studied single as well as binary gemini-conventional surfactant systems show an increase in solubilization of the PAHs. For pure systems, the MSR value of Brij 58 was found to be significantly higher than that of the other amphiphiles. Amongst the mixed surfactant systems, the solubility enhancement of anthracene is found to be maximum in the 14-E2-14 + SDS/SDBS system whereas the system14-E2-14 + Brij 58 shows a higher solubility for pyrene.

Amide type nonionic surfactants: Synthesis and corrosion inhibition evaluation against carbon steel corrosion in acidic medium

Three nonionic cleavable surfactants were prepared from the reaction of sebacic acid and antipyrine and polyethylene glycols with different molecular weights. The chemical structures of the prepared surfactants were determined using FTIR and 1H NMR spectroscopy. The surface activities of the prepared surfactants were measured based on the surface tension measurements at different temperatures. The surface parameters including: surface tension, critical micelle concentration (CMC), maximum surface excess (max) and minimum surface area. The prepared surfactants were evaluated as corrosion inhibitors to prevent the dissolution of carbon steel in 1M HCl using gravimetric method. The results showed that the inhibition efficiency of these compounds is increased by increasing their concentration, immersion time and polyethylene glycol chain length. Where the inhibitive efficiencies of the prepared surfactants at higher immersion time (120h), increased considerably to the maximum values in the range of 93.8%–98.5% at 800ppm by weight and in the range of 77.8–87.6% at 25ppm by weight. The study showed the strong relation between the surface activities of the nonionic surfactants and their inhibition efficiency in the carbon steel protection in 1M HCl.

Robust, Responsive, and Targeted PLGA Anticancer Nanomedicines by Combination of Reductively Cleavable Surfactant and Covalent Hyaluronic Acid Coating.

PLGA-based nanomedicines have enormous potential for targeted cancer therapy. To boost their stability, targetability, and intracellular drug release, here we developed novel multifunctional PLGA anticancer nanomedicines by combining a reductively cleavable surfactant (RCS), vitamin E-SS-oligo(methyl diglycol l-glutamate), with covalent hyaluronic acid (HA) coating. Reduction-sensitive HA-coated PLGA nanoparticles (rHPNPs) were obtained with small sizes of 55-61 nm and ζ potentials of -26.7 to -28.8 mV at 18.4-40.3 wt % RSC. rHPNPs were stable against dilution and 10% FBS while destabilized under reductive condition. The release studies revealed significantly accelerated docetaxel (DTX) release in the presence of 10 mM glutathione. DTX-rHPNPs exhibited potent and specific antitumor effect to CD44 + A549 lung cancer cells (IC50 = 0.52 μg DTX equiv/mL). The in vivo studies demonstrated that DTX-rHPNPs had an extended circulation time and greatly enhanced tolerance in mice. Strikingly, DTX-rHPNPs completely inhibited growth of orthotopic human A549-Luc lung tumor in mice, leading to a significantly improved survival rate and reduced adverse effect as compared to free DTX. This study highlights that advanced nanomedicines can be rationally designed by combining functional surfactants and surface coating.

Competitive Binding Interaction between Anionic Reactive Dyes and Cleavable Surfactant Micelles in Micellar-enhanced Microfiltration

Micellar-enhanced microfiltration (MEMF) was studied to remove reactive dyes from aqueous solution. In this study, simultaneous removal of Reactive Black 5 (RB5) and Reactive Orange 16 (RO16) via MEMF using palm based esterquat (PBE) as cleavable surfactant was investigated. The effect of surfactant concentration, operating pressure, and initial pH on the permeate flux, dyes and surfactant removal were discussed to assess the efficiency of MEMF process. Results obtained in this study shows that the MEMF process achieved almost complete decolourization of both RB5 and RO16 from aqueous solution.

Dynamically reconfigurable complex emulsions via tunable interfacial tensions.

Emulsification is a powerful, well-known technique for mixing and dispersing immiscible components within a continuous liquid phase. Consequently, emulsions are central components of medicine, food and performance materials. Complex emulsions, including Janus droplets (that is, droplets with faces of differing chemistries) and multiple emulsions, are of increasing importance in pharmaceuticals and medical diagnostics, in the fabrication of microparticles and capsules for food, in chemical separations, in cosmetics, and in dynamic optics. Because complex emulsion properties and functions are related to the droplet geometry and composition, the development of rapid, simple fabrication approaches allowing precise control over the droplets' physical and chemical characteristics is critical. Significant advances in the fabrication of complex emulsions have been made using a number of procedures, ranging from large-scale, less precise techniques that give compositional heterogeneity using high-shear mixers and membranes, to small-volume but more precise microfluidic methods. However, such approaches have yet to create droplet morphologies that can be controllably altered after emulsification. Reconfigurable complex liquids potentially have great utility as dynamically tunable materials. Here we describe an approach to the one-step fabrication of three- and four-phase complex emulsions with highly controllable and reconfigurable morphologies. The fabrication makes use of the temperature-sensitive miscibility of hydrocarbon, silicone and fluorocarbon liquids, and is applied to both the microfluidic and the scalable batch production of complex droplets. We demonstrate that droplet geometries can be alternated between encapsulated and Janus configurations by varying the interfacial tensions using hydrocarbon and fluorinated surfactants including stimuli-responsive and cleavable surfactants. This yields a generalizable strategy for the fabrication of multiphase emulsions with controllably reconfigurable morphologies and the potential to create a wide range of responsive materials.

Fluorescence Spectroscopy Study on the Interaction of Acetal Cleavable Anionic Surfactants and Bovine Serum Albumin

The interactions between bovine serum albumin (BSA) and two cleavable anionic surfactants, sodium 3-[(2-nonyl-1,3-dioxolan-4-yl)methoxy]propane-1-sulfonate (SNPS) and sodium 3,3′-(2-nonyl-1,3-dioxane-5,5-diyl)bis(methylene)bis(oxy)dipropane-1-sulfonate (SNDPS), have been studied by means of fluorescence spectroscopy and thermodynamic analysis. The fluorescence of BSA is quenched via a static quenching mechanism with the addition of the surfactants. The binding constants of the surfactants and proteins have been measured, with KA(SNPS) = 8.71×104 M−1 and KA(SNDPS) = 7.08 × 104 M−1, respectively. The interaction between surfactants and BSA is mainly of hydrophobic nature, based on the number of binding sites, n[n(SNPS) = 1.57, n(SNDPS) = 1.47], and the thermodynamic relationship. These results suggest that SNPS and SNDPS could be effective protein denaturants for protein separation and analysis.

Mixed Micellization Behavior of Gemini (Cationic Ester-Bonded) Surfactants with Conventional (Cationic, Anionic and Nonionic) Surfactants in Aqueous Medium

Abstract Two cationic ester-bonded cleavable gemini surfactants of different hydrophobic chain length ethane-1,2-diyl bis(N,N-dimethyl-N-alkylammoniumacetoxy)dichloride, C n H2n+1(CH3)2N+(CH2COOCH2)2N+(CH3)2C n H2n+1. 2Cl- (n-E2-n, n=12, 16), having ester linkage in the spacer, were synthesized adopting the reported procedure. Physicochemical properties of the single and binary gemini-conventional mixed micelles of different mole fractions were studied by conductivity measurements at 30 ºC. The conventional surfactants used were: DTAC (dodecyltrimethylammonium chloride), CTAC (hexadecyltrimethylammonium chloride), CPC (cetylpyridinium chloride), SDS (sodium dodecyl sulfate), SDBS (sodium dodecylbenzene sulfonate), TX-100 (t-octylphenoxypolyethoxyethanol) and Brij 58 (polyoxyethylene (20) cetyl ether). Whereas the critical micelle concentration (cmc) values for the dicationic geminis (12-E2-12 and 16-E2-16) were found to be very low as compared to the respective monomeric surfactant with the same number of carbon atoms in the hydrophobic chain per hydrophilic head group, those for all the binary systems were found to be less than the ideal cmc values studied at different mole fractions of the geminis. This synergistic interaction between the surfactants has been analyzed in the light of various theoretical models such as Clint, Rubingh, Motomura and Maeda.

Gemini ester quat surfactants and their biological activity.

Cationic gemini surfactants are an important class of surface-active compounds that exhibit much higher surface activity than their monomeric counterparts. This type of compound architecture lends itself to the compound being easily adsorbed at interfaces and interacting with the cellular membranes of microorganisms. Conventional cationic surfactants have high chemical stability but poor chemical and biological degradability. One of the main approaches to the design of readily biodegradable and environmentally friendly surfactants involves inserting a bond with limited stability into the surfactant molecule to give a cleavable surfactant. The best-known example of such a compound is the family of ester quats, which are cationic surfactants with a labile ester bond inserted into the molecule. As part of this study, a series of gemini ester quat surfactants were synthesized and assayed for their biological activity. Their hemolytic activity and changes in the fluidity and packing order of the lipid polar heads were used as the measures of their biological activity. A clear correlation between the hemolytic activity of the tested compounds and their alkyl chain length was established. It was found that the compounds with a long hydrocarbon chain showed higher activity. Moreover, the compounds with greater spacing between their alkyl chains were more active. This proves that they incorporate more easily into the lipid bilayer of the erythrocyte membrane and affect its properties to a greater extent. A better understanding of the process of cell lysis by surfactants and of their biological activity may assist in developing surfactants with enhanced selectivity and in widening their range of application.