Bolaamphiphiles Research Articles

Reproducible 3D culture of multicellular tumor spheroids in supramolecular hydrogel from cancer stem cells sorted by sedimentation field-flow fractionation

Three-dimensional (3D) cancer models, such as multicellular tumor spheroids (MCTS), are biological supports used for research in oncology, drug development and nanotoxicity assays. However, due to various analytical and biological challenges, the main recurring problem faced when developing this type of 3D model is the lack of reproducibility. When using a 3D support to assess the effect of biologics, small molecules or nanoparticles, it is essential that the support remains constant over time and multiples productions. This constancy ensures that any effect observed following molecule exposure can be attributed to the molecule itself and not to the heterogeneous properties of the 3D support. In this study, we address these analytical challenges by evaluating for the first time the 3D culture of a sub-population of cancer stem cells (CSCs) from a glioblastoma cancer cell line (U87-MG), produced by a SdFFF (sedimentation field-flow fractionation) cell sorting, in a supramolecular hydrogel composed of single, well-defined molecule (bis-amide bola amphiphile 0.25% w/v) with a stiffness of 0.4 kPa. CSCs were chosen for their ability of self-renewal and multipotency that allow them to generate fully-grown tumors from a small number of cells.The results demonstrate that CSCs cultured in the hydrogel formed spheroids with a mean diameter of 336.67 ± 38.70 µm by Day 35, indicating reproducible growth kinetics. This uniformity is in contrast with spheroids derived from unsorted cells, which displayed a more heterogeneous growth pattern, with a mean diameter of 203.20 ± 102.93 µm by Day 35. Statistical analysis using an unpaired t-test with unequal variances confirmed that this difference in spheroid size is significant, with a p-value of 0.0417 (p < 0.05).These findings demonstrate that CSC-derived spheroids, when cultured in a well-defined hydrogel, exhibit highly reproducible growth patterns compared to spheroids derived from unsorted cells, making them a more reliable 3D model for biological research and drug testing applications.

Strongly ROS-Correlated, Time-Dependent, and Selective Antiproliferative Effects of Synthesized Nano Vesicles on BRAF Mutant Melanoma Cells and Their Hyaluronic Acid-Based Hydrogel Formulation.

Cutaneous metastatic melanoma (CMM) is the most aggressive form of skin cancer with a poor prognosis. Drug-induced secondary tumorigenesis and the emergency of drug resistance worsen an already worrying scenario, thus rendering urgent the development of new treatments not dealing with mutable cellular processes. Triphenyl phosphonium salts (TPPSs), in addiction to acting as cytoplasmic membrane disruptors, are reported to be mitochondria-targeting compounds, exerting anticancer effects mainly by damaging their membranes and causing depolarization, impairing mitochondria functions and their DNA, triggering oxidative stress (OS), and priming primarily apoptotic cell death. TPP-based bola amphiphiles are capable of self-forming nanoparticles (NPs) with enhanced biological properties, as commonly observed for nanomaterials. Already employed in several other biomedical applications, the per se selective potent antibacterial effects of a TPP bola amphiphile have only recently been demonstrated on 50 multidrug resistant (MDR) clinical superbugs, as well as its exceptional and selective anticancer properties on sensitive and MDR neuroblastoma cells. Here, aiming at finding new molecules possibly developable as new treatments for counteracting CMM, the effects of this TPP-based bola amphiphile (BPPB) have been investigated against two BRAF mutants CMM cell lines (MeOV and MeTRAV) with excellent results (even IC50 = 49 nM on MeOV after 72 h treatment). With these findings and considering the low cytotoxicity of BPPB against different mammalian non-tumoral cell lines and red blood cells (RBCs, selectivity indexes up to 299 on MeOV after 72 h treatment), the possible future development of BPPB as topical treatment for CMM lesions was presumed. With this aim, a biodegradable hyaluronic acid (HA)-based hydrogel formulation (HA-BPPB-HG) was prepared without using any potentially toxic crosslinking agents simply by dispersing suitable amounts of the two ingredients in water and sonicating under gentle heating. HA-BPPB-HA was completely characterized, with promising outcomes such as high swelling capability, high porosity, and viscous elastic rheological behavior.

Hierarchical ZSM-5 nanosheets for production of light olefins and aromatics by catalytic cracking of oleic acid

The bolaform surfactant C6H13-N+(CH3)2-C6H12-N+(CH3)2-C6H12-O-C6H4-C6H4-O-C6H12-N+(CH3)2-C6H12-N+(CH3)2-C6H13 (BCPH-6-6-6) was synthesized and used to guide the synthesis of hierarchical ZSM-5 nanosheets (HZN) for use as zeolite catalysts. The number of acidic sites and the...

Synthesis and characterization of bolaform surfactants from sugar derivative and their associates with 2-aminobenzimidazole as inhibitor of zinc in 3% NaCl medium

Synthesis and characterization of bolaform surfactants from sugar derivative and their associates with 2-aminobenzimidazole as inhibitor of zinc in 3% NaCl medium

Light-induced destabilisation of oil-in-water emulsions using light-active bolaform surfactants.

External stimuli-induced destabilisation of oil-in-water emulsions is of both fundamental and technological importance. In this work we synthesize light-active bolaform-type surfactants (LABSs) and show the preparation of decane-in-water emulsions over a range of surfactant and salt concentrations. Under ultraviolet (UV) illumination, LABSs undergo trans to cis isomerization affecting their interfacial activity. Therefore when stable emulsions stabilized by LABSs are exposed to UV light, they undergo partial destabilization. To induce interfacial flow, a small amount of volatile solvent (methanol, ethanol, tetrahydrofuran, etc.) is added at the emulsification stage and in this case complete phase separation is observed. This study demonstrates a facile route to induce destabilization of surfactant-stabilized emulsions using benign solvents and minimal use of energy (UV light) and this method could be of importance in wastewater treatment, enhanced oil recovery, protein separation, etc. where emulsion destabilization is desired.

Tuning the HOMO and LUMO energy levels of dye sensitizers with electron-accepting capability and electron-drawing capability of substituents to optimize the efficiency of dye-sensitized solar cells: Approach of theoretical

In this work, for first time, TiO2 nanoparticles (TiO2 NPs) was synthesized by Dodecan-1,12-bis (triethylammoniumbromide) bolaform surfactant as template with sol-gel method. Then, prepared TiO2 NPs was crystalized in anatase phase and properties of this TiO2 NPs were compared with the properties of commercial TiO2 (P25). BET result demonstrated that compare to P25, synthesized TiO2 NPs has a very higher surface area. Both TiO2 were sensitized with N719 dye and then they used as photoanode to compare their results. The results displayed that although synthesized TiO2 NPs has lower efficiency in solar cell, it has a better fill factor compared to the P25. Also, the properties of TiO2 NPs in anatase phase in bulk and at (1 0 1) surface have been investigated by using quantum espresso (QE) package. The Band Structure and density of State (DOS) TiO2 NPs in bulk and at (1 0 1) surface have been studied. What is interesting in this article is that Dodecan-1,12-bis (triethylammoniumbromide) bolaform surfactant has been used as a templet by sol-gel method, which has increased the level of synthesized TiO2, resulting in the absorption of pigment on TiO2 increases. Absorption of more pigment on TiO2 can reduce dark stream recombination.

Bolaform Surfactant‐Induced Au Nanoparticle Assemblies for Reliable Solution‐Based Surface‐Enhanced Raman Scattering Detection

AbstractSolution‐based surface‐enhanced Raman scattering (SERS) detection typically involves the aggregation of citrate‐stabilized Au nanoparticles into colloidal assemblies. Although this sensing methodology offers excellent prospects for sensitivity, portability, and speed, it is still challenging to control the assembly process by a salting‐out effect, which affects the reproducibility of the assemblies and, therefore, the reliability of the analysis. This work presents an alternative approach that uses a bolaform surfactant, B20, to induce the plasmonic assembly. The decrease of the surface charge and the bridging effect, both promoted by the adsorption of B20, are hypothesized as the key points governing the assembly. Furthermore, molecular dynamic simulations supported the bridging effect of the B20 by showing the preferential bridging of surfactant monomers between two adjacent Au(111) slabs. The colloidal assemblies showed excellent SERS capabilities towards the rapid, on‐site detection and quantification of beta‐blockers and analgesic drugs in the nanomolar regime, with a portable Raman device. Interestingly, the application of state‐of‐the‐art convolutional neural networks, such as ResNet, allows a 100% accuracy in classifying the concentration of different binary mixtures. Finally, the colloidal approach was successfully implemented in a millifluidic chip allowing the automation of the whole process, as well as improving the performance of the sensor in terms of speed, reliability, and reusability without affecting its sensitivity.

PH-dependent micellar properties of edible biosurfactant steviol glycosides and their oil-water interfacial interactions with soy proteins

The natural sweetener steviol glycosides (STE) have been shown to be an effective biosurfactant for formulation of food emulsions. In this work, we first investigated the impact of pH on the micellar self-assembly of STE, and then evaluated the interfacial and macroscopic emulsion properties of the mixtures of STE with soy protein isolate (SPI) at different pH values (3.0 and 7.0). The results obtained show that as an edible bolaform surfactant, STE is a highly pH-sensitive system, showing interesting pH-dependent interfacial and emulsifying behaviors, which are found to strongly affect its oil-water interfacial interactions with SPI as well as the emulsion properties of the STE-SPI mixtures. Particularly, at low STE concentrations (0.1–0.4 wt%, below critical micelle concentration (CMC)), the adsorption kinetics of mixtures at pH 7.0 is mainly dominated by the STE-SPI complex, forming the interface with a plateau in the elasticity. In contrast, at pH 3.0, the simultaneous adsorption of STE and the STE-SPI complex dominates the formation of interface, resulting in a lower initial interfacial tension and a less viscoelastic film. These interfacial behaviors endow the emulsions prepared by the mixtures with an improved emulsifying ability. On the other hand, at high STE concentrations (0.8 and 1 wt%, above CMC), for the mixtures at pH 7.0, the preferential interfacial adsorption of STE over the complex leads to the formation of a simple interface mainly covered by STE. Contrastly, the interfaces at pH 3.0 are still complex and dominated simultaneously by STE and STE-SPI complex. However, the poor emulsifying capacity of STE at pH 3.0 greatly disturbs the emulsifying properties of the mixtures, resulting in the large oil droplets and the consequent phase separation of emulsions.

Synthesis of ω‐Amino‐Functionalized Alkyl Quaternary Ammonium Surfactants

AbstractA versatile four‐step synthetic route towards a series of new ω‐amino‐functionalized alkyl quaternary ammonium bolaform surfactants was developed. The key step in the synthesis is the ring opening of a macrocyclic lactone to form long‐chain ω‐hydroxy amide precursors. The asymmetric bolaform surfactants are structurally analogous to the ω‐hydroxy quaternary ammonium surfactants that have been previously shown to form small micelles and have been exploited as soft templates in the preparation of super‐microporous materials.

Linking molecular structures of yeast-derived biosurfactants with their foaming, interfacial, and flotation properties

Yeast-derived bola amphiphiles have attracted growing attention in various industrial sectors as green reagents. However, their physico-chemical properties relevant to mineral separation by froth flotation are poorly explored. To bridge this gap, we studied the foaming, interfacial, and flotation properties of acidic sophorolipid (ASL), acidic glucolipid (GL) and alcoholic glucoside (GS) obtained from strain engineering of the yeast Candida bombicola by molecular editing of the headgroups. Bench-scale flotation testing of a copper sulfide ore showed that ASL can effectively separate copper sulfides (85% recovery at 20% grade), GL is less effective (ca. 60% recovery and 13% grade), while GS is a poor collector. To understand this trend, we studied the interfacial and foaming properties of these three biosurfactants. The surface tension study reveals that, contrary to GS, self-assembly of both ASL and GL at the air–water interface is pH-responsive, suggesting that both the biosurfactants acquire a Π-shape. The dependence of the foaming properties of all the three surfactants on pH and concentration does not correlate with the trends in the static surface tension, suggesting the critical roles of dynamic factors, interfacial elasticity and interfacial viscosity. Hydrophobicity of djurleite (a model copper sulphide) in the presence of the three surfactants was assessed using the contact angle and Hallimond flotation methods. ASL and GL only float the pure mineral at alkaline pH, which is consistent with the contact angle data. In contrast, even though GS does not have a significant effect on contact angle, it floats djurleite in a wide pH range, which is explained by the mechanical entrainment of hydrophilic mineral particles in rich GS foams. Overall, these results demonstrate the potential of carboxylic bola biosurfactants for the recovery of copper sulfides from ores. They also bring new insights into the interfacial and foaming properties of bola biosurfactants, which can assist their introduction into other industries.

Synthesis of bolaform surfactants from recycled poly(ethylene terephthalate) waste

In this study, bolaform surfactants have been prepared from recycled poly(ethylene terephthalate) monomers through an efficient process. Bis(hydroxyethyl) terephthalate (BHET) and terephthalic acid (TPA) have been used as precursor molecules for the synthesis of organophosphorus surfactants. With a yield of 73%, the reaction between BHET and triethyl phosphate resulted in the bis(2-((triethoxy(hydroxy)-l5-phosphaneyl)oxy)ethyl) terephthalate (BHETEO) sample. From TPA as a precursor molecule in a three-step reaction process, TPTEOH compound has been obtained with a yield of 58%. The physicochemical properties such as solubility, photosensitivity, zeta potential, hydrodynamic size, and thermogravimetric analyses of both surfactants have been studied. The bolaform surfactants showed stability under ultraviolet radiation. The Dynamic Light Scattering analysis displayed an aggregate size of 65.7 nm for BHETEO sample, without the influence of temperature. In contrast, the aggregate size of 144 nm for TPTEOH was strongly influenced by temperature. The BHETEO and TPTEOH samples presented Zeta Potentials of −21.7 mV and −1.06 mV, respectively. The results showed BHETEO and TPTEOH samples to have self-assembling properties with aggregation forms dependent on the polarity of the solvents. Therefore, the development of bolaform surfactants represents an alternative way to use monomers from PET waste with promising applications.

Dual-template synthesis of hierarchically layered titanosilicate-1 zeolites for catalytic epoxidation of cyclooctene

A one-pot facile route for preparing hierarchically layered titanosilicate-1 (LTS-1) zeolites with stable interlayered mesopores was proposed by integrated using bolaform surfactant (BC ph-12-6-6 ) and tetrapropyl ammonium hydroxide (TPAOH) as dual templates. By tuning the molar ratios of BC ph-12-6-6 /TPAOH from 5/0 to 5/9, the corresponding LTS-1 samples showed continuous transformations in morphology and intensified degrees of intergrowth by TS-1 nanosheets, resulting in an effective interlayer self-pillaring to avoid the excessive collapse after the removal of the occupied templates by calcination. Moreover, the LTS-1 samples by dual-template synthesis manifested enriched contents of mononuclear octahedrally coordinated Ti species (“TiO 6 ”). Benefitted by the highly patulous structure and more accessible Ti active sites predominated with high-performance “TiO 6 ” species, the LTS-1 catalysts by dual-template synthesis exhibited a superior catalytic activity in the epoxidation of cyclooctene compared with the layered TS-1 directed by sole template of BC ph-12-6-6 and the conventional bulk TS-1. It is reasonable to expect that the demonstrated work has important implications for the design and facile synthesis of layered titanosilicate zeolite catalysts with a stably hierarchical structure and tunable catalytic oxidation activities by an optimized distribution of titanium coordination states containing the coordinated “TiO 4 ” and “TiO 6 ” species. • One-pot dual-template synthesis of hierarchically layered titanosilicate-1 (LTS-1). • Effective interlayer self-pillaring by integrated templating of BC ph-12-6-6 and TPAOH. • LTS-1 manifests enriched contents of mononuclear octahedrally coordinated Ti species (“TiO 6 ”). • Improved catalytic epoxidation performances by the highly patulous structure and more accessible Ti active sites.

Biomedically Relevant Applications of Bolaamphiphiles and Bolaamphiphile-Containing Materials.

Bolaamphiphiles (BAs) are structurally segmented molecules with rich assembly characteristics and diverse physical properties. Interest in BAs as standalone active agents or as constituents of more complex therapeutic formulations has increased substantially in recent years. The preorganized amphiphilicity of BAs allows for a range of biological activities including applications that rely on multivalency. This review summarizes BA-related research in biomedically relevant areas. In particular, we review BA-related literature in four areas: gene delivery, antimicrobial materials, hydrogels, and prodrugs. We also discuss several distinguishing characteristics of BAs that impact their utility as biomedically relevant compounds.

Cationic Bola Form Metallosurfactants Based on Isothiouronium, Synthesis and Anti-Microbial Activity

Abstract Two series of well-defined dimeric metallo-bolaamphiphiles (bola surfactants) with the coordinated metal ions (Cu, Co, Zn) were prepared. These oligomeric surfactants consist of simple monomeric cationic surfactant fragments which are coupled via the hydrophilic ammonium chloride head groups by C6 and C12 spacer groups of different lengths. FTIR and 1HNMR identification techniques confirmed the obtained products. Measurements of surface tensions showed that the synthesized Bola amphiphiles have the desired, relatively low critical micelle formation concentrations (CMC). Bola amphiphiles with long spacer groups (C12) have a pronounced surface activity. The properties of these cationic surfactant oligomers in aqueous solution such as micellization and surface activity were discussed in relation to spacer group. In addition, the synthesized compounds were examined for their anti-microbial activity using the agar diffusion technique.

Anthranilamide-based Short Peptides Self-Assembled Hydrogels as Antibacterial Agents

In this study, we describe the synthesis and molecular properties of anthranilamide-based short peptides which were synthesised via ring opening of isatoic anhydride in excellent yields. These short peptides were incorporated as low molecular weight gelators (LMWG), bola amphiphile, and C3-symmetric molecules to form hydrogels in low concentrations (0.07–0.30% (w/v)). The critical gel concentration (CGC), viscoelastic properties, secondary structure, and fibre morphology of these short peptides were influenced by the aromaticity of the capping group or by the presence of electronegative substituent (namely fluoro) and hydrophobic substituent (such as methyl) in the short peptides. In addition, the hydrogels showed antibacterial activity against S. aureus 38 and moderate toxicity against HEK cells in vitro.

Bolaform surfactant-directed synthesis of TS-1 zeolite nanosheets for catalytic epoxidation of bulky cyclic olefins

Hierarchical TS-1 nanosheets were hydrothermally synthesized by using a bolaform surfactant as the structure-directing agent and exhibited improved catalytic performance and superior recyclability in the epoxidation of cyclohexene and cyclooctene.

Multiple modulations for supramolecular hydrogels of bola-form surfactants bearing rigid and flexible groups.

A series of bola-form surfactants with two identical azobenzene ends separated by a flexible chain but different cationic heads were synthesized. These amphiphilic molecules exhibited rich self-assembly properties in aqueous solutions. The physical characterizations demonstrated that the cationic heads showed a decisive influence on both the gelation behavior and the gel strength. The surfactant with a trimethylammonium head group did not form a hydrogel even at a higher concentration, yet it promoted the gelation of pyridinium and methylimidazolium head bearing surfactants, which formed hydrogels but could not boost each other's gelation capability. Besides the heating induced reversible gel-sol transition, the UV light irradiation also triggered the change of gel to sol while the irradiation with visible light led to a reverse process. Through the addition of cyclodextrins, the hydrogels transformed into sols, while the sols reverted to gels accompanied by the addition of competitive guest molecules. The surfactant hydrogels displayed a stimulus-response to both anionic and cationic additives based on different mechanisms, and reverse order of addition of the external guest molecules and host cyclodextrins also resulted in the modulation of the gel-sol transition. By the combination of photo- and chemical-stimuli, multiple responses on the transformations between the gel and sol were realized.

Strain-Stiffening in Dynamic Supramolecular Fiber Networks.

The cytoskeleton is a highly adaptive network of filamentous proteins capable of stiffening under stress even as it dynamically assembles and disassembles with time constants of minutes. Synthetic materials that combine reversibility and strain-stiffening properties remain elusive. Here, strain-stiffening hydrogels that have dynamic fibrous polymers as their main structural components are reported. The fibers form via self-assembly of bolaamphiphiles (BA) in water and have a well-defined cross-section of 9 to 10 molecules. Fiber length recovery after sonication, H/D exchange experiments, and rheology confirm the dynamic nature of the fibers. Cross-linking of the fibers yields strain-stiffening, self-healing hydrogels that closely mimic the mechanics of biological networks, with mechanical properties that can be modulated by chemical modification of the components. Comparison of the supramolecular networks with covalently fixated networks shows that the noncovalent nature of the fibers limits the maximum stress that fibers can bear and, hence, limits the range of stiffening.

Hierarchical MFI Zeolites with a Single-Crystalline Sponge-Like Mesostructure.

Single-crystalline sponge-like MFI mesoporous zeolites (SSMZs) have been synthesized by using bolaform surfactants with an axial chiral binaphthyl core in the hydrophobic tail and triquaternary ammonium head groups, as bifunctional organic structure-directing agents (OSDAs). By changing the length of alkyl chain between a triquaternary ammonium head group and a binaphthyl group from 4 to 10 carbons, SSMZs with high specific surface area (382-434 m2 g-1 ), abundant micropore-mesopore connectivity, and uniform mesopore diameter (4-10 nm) were obtained. OSDAs with an alkyl chain length of 11 and 12 carbons led to the formation of nanorod-constructed mesoporous MFI zeolites. A geometrical matching between the cylindrical arrangement of the binaphthyl groups and the zeolitic framework is speculated to be the key factor for the formation of mesoporous zeolites. The SSMZ zeolites, with abundant mesopores beneficial for the diffusion of reactants, exhibited significantly higher catalytic efficiencies than those of the conventional ZSM-5 with a microcrystal morphology (≈1.5 μm).

Directed OmniChange Evolution Converts P450 BM3 into an Alkyltrimethylammonium Hydroxylase.

Cetyl-trimethylammonium bromide (CTAB) is a widely used cationic surfactant that is biodegradable in nature. CTAB biodegradation requires hydroxylation in the first step, which is rate-limiting and crucial for solubility in water. In this study, the OmniChange multi-site mutagenesis method was applied to reengineer the P450 BM3 substrate specificity towards the hydroxylation of CTAB by simultaneous mutagenesis of four previously reported positions (R47, Y51, F87, and L188). 1740 clones from the P450 BM3 OmniChange library were screened with the NADPH depletion assay. A total of 696 clones were rescreened with the NADPH depletion and an Ampliflu™ Red/ horseradish peroxidase based H2 O2 detection assay. Several improved P450 BM3 variants were identified and finally four were kinetically characterized with respect to CTAB hydroxylation, based on both performance and coupling efficiency. Based on NADPH consumption, the P450 BM3 variant P3A8 (R47E/Y51M/F87V/L188E) displayed an initial activity (64.9±4.8 s-1 , 13.5-fold increased activity compared with wild-type P450 BM3), which nearly matches the specific activity for its natural fatty acid substrate (palmitic acid (32-122 s-1 )). Variant P3A8 showed high coupling efficiency (92.5 %), whereas wild-type P450 BM3 displayed a low coupling efficiency (0.5 %). HPLC-MS/MS detection confirmed that P3A8 and P2E7 (R47D/Y51L/F87V/L188A) form 13 and 35 times more 2-hydroxylated CTAB than P450 BM3. In addition, di-hydroxylated CTAB products were detected for all four investigated P450 BM3 variants (up to a yield of 77 %; P3A8). Di-hydroxylated quaternary amines are highly interesting bolaform surfactants with a high hydrophilicity (surface contact angle: θ=16.7°).