Self-aggregation Properties Research Articles

Methoxy-enriched cationic stilbenes as anticancer therapeutics.

Stilbene-based compounds are largely described for their antioxidant activity. But their use as anticancer chemotherapeutics is hampered by poor pharmacokinetic properties and non-selectivity towards cancer and non-cancer potency. To overcome these drawbacks, twin chain cationic lipid conjugated, methoxy-enriched stilbene derivatives were designed, synthesized and evaluated for their anticancer potency. Our findings reveal that HMSC16, a molecule with the highest number of methoxy groups and with C16-twin chain lipid, is the most potent as well as the most selective anticancer agent when compared to the other synthesized derivatives and commercially available stilbene-based drug, tamoxifen, and resveratrol. To justify these results, we have conducted a series of mechanistic experiments where we found that HMSC16 induced ROS generation, apoptosis, and autophagy by affecting the mitochondrial, lysosomal and nuclear pathways. Further cell cycle analysis data reveals that HMSC16 not only induces cell death but is also involved in the arrest of the cell cycle at the sub-G1 phase. Moreover, HMSC16 showed self-aggregation property owing to a possibly favorable hydrophilic-lipophilic balance. The self-aggregation property of HMSC16 allowed it to entrap hydrophobic drugs, withaferin. With entrapped withaferin, HMSC16 showed additive if not synergistic cell killing effect in HeLa cells. From the above results, we concluded that HMSC16 can be used not just as a drug but also as a drug delivery agent.

A gut bacterial amyloid promotes α-synuclein aggregation and motor impairment in mice

Amyloids are a class of protein with unique self-aggregation properties, and their aberrant accumulation can lead to cellular dysfunctions associated with neurodegenerative diseases. While genetic and environmental factors can influence amyloid formation, molecular triggers and/or facilitators are not well defined. Growing evidence suggests that non-identical amyloid proteins may accelerate reciprocal amyloid aggregation in a prion-like fashion. While humans encode ~30 amyloidogenic proteins, the gut microbiome also produces functional amyloids. For example, curli are cell surface amyloid proteins abundantly expressed by certain gut bacteria. In mice overexpressing the human amyloid α-synuclein (αSyn), we reveal that colonization with curli-producing Escherichia coli promotes αSyn pathology in the gut and the brain. Curli expression is required for E. coli to exacerbate αSyn-induced behavioral deficits, including intestinal and motor impairments. Purified curli subunits accelerate αSyn aggregation in biochemical assays, while oral treatment of mice with a gut-restricted amyloid inhibitor prevents curli-mediated acceleration of pathology and behavioral abnormalities. We propose that exposure to microbial amyloids in the gastrointestinal tract can accelerate αSyn aggregation and disease in the gut and the brain.

Amphiphilic drug-peptide-polymer conjugates based on poly(ethylene glycol) and hyperbranched polyglycerol for epidermal growth factor receptor targeting: the effect of conjugate aggregation on in vitro activity.

Numerous peptide-drug conjugates have been developed over the years to enhance the specificity and selectivity of chemotherapeutic agents for tumour cells. In our present work, epidermal growth factor receptor targeting drug-peptide conjugates were prepared using GE11 and D4 peptides. To ensure the drug release, the cathepsin B labile GFLG spacer was incorporated between the targeting peptide and the drug molecule (daunomycin), which significantly increased the hydrophobicity and thereby decreased the water solubility of the conjugates. To overcome the solubility problem, drug-peptide-polymer conjugates with systematic structural variations were prepared, by linking poly(ethylene glycol) (PEG) or a well-defined amino-monofunctional hyperbranched polyglycerol (HbPG) directly or via a pentaglycine spacer to the targeting peptides. All the drug-peptide-polymer conjugates were water-soluble as confirmed by turbidimetric measurements. The results of the in vitro cell viability and cellular uptake measurements on HT-29 human colon adenocarcinoma cells proved that the HbPG and the PEG highly influenced the biological activity. The conjugation of the hydrophilic polymer resulted in the amphiphilic character of the conjugates, which led to self-aggregation and nanoparticle formation that decreased the cellular uptake above a specific aggregation concentration. On the other hand, the hydrodynamic volume and the different polymer chain topology of the linear PEG and the compact hyperbranched HbPG also played an important role in the biological activity. Therefore, in similar systems, the investigation of the colloidal properties is inevitable for the better understanding of the biological activity, which can reveal the structure-activity relationship of amphiphilic drug-peptide-polymer conjugates for efficient tumour targeting.

The surface adsorption, aggregate structure and antibacterial activity of Gemini quaternary ammonium surfactants with carboxylic counterions.

A group of Gemini quaternary ammonium surfactants with the formula CnH2n+1CONH(CH2)2N+(CH3)2(CH2)2N+(CH3)2(CH2)2 NHCOCnH2n+1 · 2Y (n = 11, 13 and 15, Y = HCOO−, CH3COO− and CH3CHOHCOO−) have been synthesized by a counterion conversion process and characterized by Fourier transform infrared spectroscopy and mass spectroscopy. Their adsorption and self-aggregation properties are investigated by surface tension, conductivity, dynamic light scattering and transmission electron microscopy (TEM) measurements. The results show that these surfactants reduce the surface tension of water to a minimum value of 26.51 mN m−1 at a concentration of 5.72 × 10−2 mmol l−1. Furthermore, the increased alkyl chain length of the carboxylic counterions leads to the increased critical micelle concentration, the decreased degree of counterion binding (β) and the decreased self-assembly tendency, but the minimum area per surfactant molecule (Amin) adsorbed at the air–aqueous solution are similar. TEM images reveal that these surfactants self-assemble spontaneously into aggregates with vesicle or bilayer structures. It is also found that they have superior antibacterial activity at a concentration of 0.1 g l−1. The high surface activity and high antibacterial activity of the Gemini quaternary ammonium salt surfactants containing different carboxylic counterions bring more possibilities for the application in the field of biomedicine.

Contrasting hydration dynamics in DME and DMSO aqueous solutions: A combined optical pump-probe and GHz-THz dielectric relaxation investigation

Addition of co-solvents could introduce perturbation in the H-bond dynamics of water and the extent of perturbation is mostly dependent on the H-bond formation affinity of the respective co-solvent. In this contribution we have studied the H-bond dynamics of water in presence of two co-solvents, 1,2-dimethoxy ethane (DME) and dimethyl sulfoxide (DMSO) using two complementary experimental techniques to compare global (through dielectric relaxation study in the GHz-THz frequency domain) as well as local (through FTIR and optical single color pump-probe studies) hydration environment and dynamics in the two binary mixtures. Due to the presence of sulfur atom DMSO tends to form H-bonds with polar water molecules and subsequently forms various stable H-bonded clusters. DME, owing to its higher carbon content and being a planer molecule, struggles to form H-bonds. DME is rather inclined to form hydrophobic aggregates resulting in a random orientation of water around those hydrophobic interfaces. The difference in the affinity of H-bond formation and self-aggregation properties of the co-solvents are found to modulate the hydration dynamics in contrasting manners as evidenced from the experimental findings.

Preparation of nanocomposites with epoxy resins and thiol-functionalized carbon nanotubes by thiol-ene click reaction

Carbon nanotubes (CNTs) have attracted increasingly interest in preparing CNTs/epoxy nanocomposites for improving thermal and mechanical properties. The well distribution of prime CNTs in epoxy matrix is still a challenge due to the strong interaction among nanotubes and property of self-aggregation. Here, we report a highly efficient approach to functionalize prime CNTs by a thiol-ene click reaction between double bonds of CNTs and thiol groups of mercaptans, and the resulted in thiol-functionalized CNTs with different chemical chains show well dispersion in ethyl acetate and epoxy. The thiol-functionalized CNTs show a positive effect on reinforcing and toughening diglycidyl ether of bisphenol-A (DGEBA). With an increase in the thiol-functionalized CNTs content, the mechanical and thermal properties of the CNTs/DGEBA nanocomposites, including tensile, flexural and impact strengths, and thermal conductivity, increase first and then decrease. The maximum improvements on the tensile, flexural, impact strengths and thermal conductive were 43.75%, 25.11%, 196.44% and 33.81%, respectively. These grafted mercaptans chains play a bridging action between CNTs and epoxy matrix to supply a strong interaction, substantiated by their good rheological property and ductile SEM micrographs. Both the simple method of thiol-functionalized CNTs and preparation of CNTs/DGEBA nanocomposites will supply dependable data for wide application of CNTs. • A highly efficient thiol-ene click reaction was used to functionalize prime CNTs. • Thiol-functionalized CNTs showed well dispersion in ethyl acetate and epoxy. • Thiol-functionalized CNTs could reinforce and toughen diglycidyl ether of bisphenol-A. • A strong interaction between CNTs and epoxy matrix was substantiated by rheological property and SEM.

Random copolymerization realized high efficient polymer solar cells with a record fill factor near 80%

In this work, we successfully achieved a record fill factor (FF) of near 80% by using random copolymerization strategy to precisely control the morphology of active layer for polymer solar cells (PSCs). A series of random copolymers were synthesized by random copolymerization of a self-assembly third unit into the multithiophene-based polymer matrix. The random copolymers possess excellent room temperature processing performance due to their relatively weaker self-aggregation properties. More importantly, despite the non-irregular sequence of random copolymers, the planarity of the third unit favored by the S⋅⋅⋅O intramolecular interaction still induced a face-on orientation of the random copolymers and formed a homogeneously fibril-like interpenetrating network structure in the blend films. Ultimately, the random polymer-based device achieved a remarkably high fill factor (FF) near 80% without any treatment, even approaching to the values of the inorganic materials-based solar cells.

Discovering new M-quinolate materials: theoretical insight into understanding the charge transport, electronic, self-aggregation properties in M-quinolate materials (M = Li, Na, K, Rb, Cs, Cu, Ag, and Au)

A series of M-quinolate complexes were theoretically investigated to understand the effect of metal ions on electronic and charge transport properties by employing density functional theory simulation. It was found that both electronic and carrier transport properties in M-quinolate materials significantly depend on singly oxidized metal ions. In particular, Csq apparently showed an excellent advantage over other M-quinolate materials (M = Li, Na, K, Rb, Cs, Cu, Ag, and Au) in terms of electron mobility and injection. In addition, the dimerization and vertical detachment energies of all M-quinolate materials were compared to understand self-aggregation effect on carrier transport. As a result, it is expected that Csq is not only likely to be present in dimer form, but also reduce the density of electron traps in electron transporting materials.

Phase Behavior of Ester Based Anionic Surfactants: Sodium Alkyl Sulfoacetates

Ester based anionic surfactant—sodium lauryl sulfoacetate (SLSA)—is one of the most important surface-active ingredients in several personal care products however no scientific report is available regarding its lyotropic and thermotropic phase behavior in water. In the present study, SLSA and its congener sodium myristyl sulfoacetate (SMSA) are investigated for their self-aggregation properties in aqueous system. Phase transition temperature of these surfactant–water mixtures is determined by differential scanning calorimetry (DSC). Their lyotropic and thermotropic phase behavior in water are investigated by polarized optical microscopy (POM), small-angle X-ray scattering (SAXS) and wide-angle X-ray scattering (WAXS). These surfactants predominantly exist as different types of self-assembled lamellar phases along with or without solid crystalline phases in aqueous system.

Fluorous Property of a Short Perfluoroalkyl-Containing Compound Realized by Self-Assembled Monolayer Technique on a Silicon Substrate

Abstract Fluorous properties represented by water-and-oil repellency are perfluoroalkyl (Rf) compound-specific characteristics, which are widely used for surface coating of glass, electronic devices and textiles for preventing water and grease fouling. According to the stratified dipole-arrays (SDA) theory, the minimum Rf length of (CF2)7 is theoretically necessary for realizing fluorous properties. Unfortunately, however, production of compounds involving this chemical unit is strictly banned because of concerns of environmental pollution, which is a big dilemma. Here, we show that the fluorous properties can be realized by self-assembled monolayer (SAM) even with a short Rf-containing compound, since the SAM technique makes the best use of the self-aggregation property of the Rf groups, and it readily makes the molecules immobile.

Arabinose substitution effect on xylan rigidity and self-aggregation

Substituted xylans play an important role in the structure and mechanics of the primary cell wall of plants. Arabinoxylans (AX) consist of a xylose backbone substituted with arabinose, while glucuronoarabinoxylans (GAX) also contain glucuronic acid substitutions and ferulic acid esters on some of the arabinoses. We provide a molecular-level description on the dependence of xylan conformational, self-aggregation properties and binding to cellulose on the degree of arabinose substitution. Molecular dynamics simulations reveal fully solubilized xylans with a low degree of arabinose substitution (lsAX) to be stiffer than their highly substituted (hsAX) counterparts. Small-angle neutron scattering experiments indicate that both wild-type hsAX and debranched lsAX form macromolecular networks that are penetrated by water. In those networks, lsAX are more folded and entangled than hsAX chains. Increased conformational entropy upon network formation for hsAX contributes to AX loss of solubility upon debranching. Furthermore, simulations show the intermolecular contacts to cellulose are not affected by arabinose substitution (within the margin of error). Ferulic acid is the GAX moiety found here to bind to cellulose most strongly, suggesting it may play an anchoring role to strengthen GAX-cellulose interactions. The above results suggest highly substituted GAX acts as a spacer, keeping cellulose microfibrils apart, whereas low substitution GAX is more localized in plant cell walls and promotes cellulose bundling.

Enhancement of Self-Aggregation Properties of Linear Elastin-Derived Short Peptides by Simple Cyclization: Strong Self-Aggregation Properties of Cyclo[FPGVG]n, Consisting Only of Natural Amino Acids

Elastin-like peptides (ELPs) consist of distinctive repetitive sequences, such as (VPGVG) n, exhibit temperature-dependent reversible self-assembly (coacervation), and have been considered to be useful for the development of thermoresponsive materials. Further fundamental studies evaluating coacervative properties of novel nonlinear ELPs could present design concepts for new thermoresponsive materials. In this study, we prepared novel ELPs, cyclic (FPGVG) n (cyclo[FPGVG] n, n = 1-5), and analyzed their self-assembly properties and structural characteristics. Cyclo[FPGVG] n ( n = 3-5) demonstrated stronger coacervation capacity than the corresponding linear peptides. The coacervate of cyclo[FPGVG]5 was able to retain water-soluble dye molecules at 40 °C, which implied that cyclo[FPGVG]5 could be employed as a base material of DDS (drug delivery system) matrices and other biomaterials. The results of molecular dynamics simulations and circular dichroism measurements suggested that a certain chain length was required for cyclo[FPGVG] n to demonstrate alterations in molecular structure that were critical to the exhibition of coacervation.

Asphaltene fractionation based on adsorption onto calcium carbonate: Part 3. Effect of asphaltenes on wax crystallization

Asphaltenes fractionation procedures were developed and tested in two preceding articles (doi: https://doi.org/10.1016/j.colsurfa.2016.02.011, doi: https://doi.org/10.1016/j.colsurfa.2016.11.035), and asphaltene fractions were characterized in terms of composition, adsorption and self-aggregation properties. In this article, the effect of asphaltene fraction on wax crystallization was studied. Asphaltene fractionation on calcium carbonate was developed further to a column separation procedure, which yielded asphaltene fractions with even larger differences according to FTIR analysis. Wax crystallization was studied using differential scanning calorimetry (DSC), cross-polarized microscopy (CPM), rheometry, and pour point tests (PPT). Asphaltenes were found to change wax crystal morphology and decrease gel yield strength with increasing concentration. The effect on wax appearance temperature (WAT) was generally less. The greatest effect on WAT and pour point was made by bulk asphaltenes, which is the lowest polarity fraction from separation on calcium carbonate. Irreversibly adsorbed asphaltenes, containing significant amounts of carbonyl, carboxylic or derivative groups, induced the largest changes in wax crystal morphology. Still, high pour point and gel yield strength indicated low performance for this fraction. Overall, wax inhibition performance tended to be best for asphaltene fractions with low solubility and mixed functional groups. In isothermal titration calorimetry (ITC), unfractionated whole asphaltenes interacted more strongly with crystallized wax than asphaltene fractions bulk and irreversibly adsorbed. The findings indicate that wax crystallization is influenced the most by an ensemble of asphaltenes with different functional groups, rather than groups with more distinct properties.

Studies on the physicochemical properties of synthesized tailor-made gemini surfactants for application in enhanced oil recovery

In this study, the physicochemical properties of a series of synthesized cationic gemini surfactants with different aliphatic carbon spacer lengths were investigated as an effective, unconventional chemical agent for practical application in enhanced oil recovery (EOR) from mature reservoirs. The self-aggregation property at low concentrations was confirmed by tensiometry measurements. Critical micelle concentration (CMC) values increased with temperature rise. Thermal stability experiments showed no surfactant degradation over a long time period. The surfactants showed good tolerance to salt addition, confirming their functionality even under high salinity conditions. Rheological studies discussing the effect of the nature of micelles on the viscosity of surfactant solutions was studied as a function of concentration and temperature. Ultralow interfacial tension (IFT) values of the order of 10–2 to 10–3mN/m was obtained at the oil-aqueous interface. Zeta potential and contact angle measurements revealed favorable rock alteration from intermediate-wet to water-wet state by the mechanism of ion-pair interactions. Sandpack flooding studies using surfactant-polymer formulations yielded additional oil recoveries of 29.83%, 31.73%, 33.83% and 34.55% for 14-3-14, 14-4-14, 14-5-14 and 14-6-14 systems respectively.

Synthesis, spectroscopic studies and biological evaluation of acridine derivatives: The role of aggregation on the photodynamic efficiency

Two new photoactive compounds (1 and 2) derived from the 9-amidoacridine chromophore have been synthesized and fully characterized. Their abilities to produce singlet oxygen upon irradiation have been compared. The synthesized compounds show very different self-aggregating properties since only 1 present a strong tendency to aggregate in water. Biological assays were conducted with two cell types: hepatoma cells (Hep3B) and human umbilical vein endothelial cells (HUVEC). Photodynamic therapy (PDT) studies carried out with Hep3B cells showed that non-aggregating compound 2 showed photoxicity, ascribed to the production of singlet oxygen, being aggregating compound 1 photochemically inactive. On the other hand suspensions of 1, characterized as nano-sized aggregates, have notable antiproliferative activity towards this cell line in the dark.

Gas Phase Studies of the Amyloid-β Peptide

The amyloid-β (Aβ) peptide is an amphiphilic peptide that exhibits self-aggregating properties forming the amyloid fibrils that can be found in the brains of Alzheimer patients. Today it is believed that that it is the soluble Aβ oligomers rather than the mature fibrils that are the main neurotoxic species. These small peptide-assembles are known to associate with membranes and form pores that can transport Ca2+ into the cell, which in part could be responsible for their neurotoxic properties. However, most biophysical methods that have been developed to study Aβ target either the monomer or the mature fibrils, and not the low abundance and polydisperse oligomers.We have developed a soft ionization mass spectrometry (MS) method that retains and detects these non-covalent oligomer interactions in the gas phase. And since MS is a non-averaging technique the aggregation kinetics for different oligomeric species, as well as reduced and oxidized peptides, could be followed simultaneously. The high-resolution MS was also coupled to an ion mobility spectrometer that separates ions of the same m/z according to collisional cross section, yielding information about peptide conformations in the gas phase. Additionally, peptide interactions with other molecules, such as membrane mimicking detergents can be monitored. Large complexes between Aβ(1-40) and detergent micelles was shown to survive in the MS and could be identified. Detergent head group charges seem to be essential for peptide-micelle interactions, both in the gas phase and in solution, as no structure induction is observed upon addition of non-ionic detergent. The developed methodology is promising for future detection of pore-forming oligomers in micelles, and probably also in other more sophisticated membrane models.

Characterization of the micelle structure of oleic acid-based gemini surfactants: effect of stereochemistry.

In this study, we synthesize a novel oleic acid-based gemini surfactant with carboxylate headgroups, and study the effect of stereochemistry (anti- vs. syn-) on self-aggregation properties in water. We investigate these properties using phase diagrams, static surface tension, and one-dimensional and two-dimensional nuclear magnetic resonance (NMR) measurements. We find that a phase transition from a hexagonal liquid crystal (H1) phase to a lamellar liquid crystal (Lα) phase occurs at a lower surfactant concentration in the syn form, when compared with the anti form. In addition, the syn form gemini surfactant forms micelles with a close packing of the headgroups via hydrogen bonding. This was supported by static surface tensiometry; the area occupied by surfactant molecules at the air/aqueous solution interface is smaller for the syn form than for the anti form. We propose that, for the syn form gemini surfactant, the closer packing of the headgroups as well as the hydrogen bonding network around the micelle interface prevent water penetration into the hydrophobic part of the micelle.

Real-Time Trafficking of Agrobacterium Virulence Protein VirE2 Inside Host Cells.

A. tumefaciens delivers T-DNA and virulence proteins, including VirE2, into host plant cells, where T-DNA is proposed to be protected by VirE2 molecules as a nucleoprotein complex (T-complex) and trafficked into the nucleus. VirE2 is a protein that can self-aggregate and contains targeting sequences so that it can efficiently move from outside of a cell to the nucleus. We adopted a split-GFP approach and generated a VirE2-GFP fusion which retains the self-aggregating property and the targeting sequences. The fusion protein is fully functional and can move inside cells in real time in a readily detectable format: fluorescent and unique filamentous aggregates. Upon delivery mediated by the bacterial type IV secretion system (T4SS), VirE2-GFP is internalized into the plant cells via clathrin adaptor complex AP2-mediated endocytosis. Subsequently, VirE2-GFP binds to membrane structures such as the endoplasmic reticulum (ER) and is trafficked within the cell. This enables us to observe the highly dynamic activities of the cell. If a compound, a gene, or a condition affects the cell, the cellular dynamics shown by the VirE2-GFP will be affected and thus readily observed by confocal microscopy. This represents an excellent model to study the delivery and trafficking of an exogenously produced and delivered protein inside a cell in a natural setting in real time. The model may be used to explore the theoretical and applied aspects of natural protein delivery and targeting.

Dinuclear (N∧C∧N) Pincer Pt(II) Complexes with Bridged Organometallic Linkers: Synthesis, Structures, Self-Aggregation, and Photophysical Properties

A new family of cationic dinuclear cyclometalated Pt(II) complexes containing an organometallic assembling ligand has been reported. The general formulas for these compounds is as follow: [R-(N∧C∧N)Pt—L-L—Pt(N∧C∧N)-R][X]2, where L-L = [Cp*Ir-p-(η4-C6H4S2)], R = H, X = OTf (5); R= CF3–, X = OTf (6a), SbF6 (6b); L-L = [Cp*Ir-p-(η4-C6H4Se2)] R= CF3–, X = OTf (7a), SbF6 (7b). In these coordination assemblies two cyclometalated R-(N∧C∧N)Pt moieties are held by either η4-dithio-p-benzoquinone complex [Cp*Ir-p-(η4-C6H4S2)] (3) or η4-diseleno-p-benzoquinone complex [Cp*Ir-p-(η4-C6H4Se2)] (4). The molecular structures of the known complex [4-CF3-(N∧C∧N)PtCl] as well as two compounds of the above family [(N∧C∧N)Pt–Cp*Ir-p-(η4-C6H4S2)—Pt(N∧C∧N)][CF3SO3]2 (5) and [CF3-(N∧C∧N)Pt—Cp*Ir-p-(η4-C6H4S2)—Pt(N∧C∧N)-CF3][CF3SO3]2 (6a) were ascertained by single crystal X-ray diffraction study and confirmed the formation of the target molecules. The solid-state packing of 5 and 6a confirms the presence π–π and short Pt···Pt in...

Investigation into Sonogashira reaction on 5-iodo-1-(phenyl/p-halophenyl)imidazole-4-carbonitrile compounds

ABSTRACTInvestigation into Sonogashira reaction on 5-iodo-1-(phenyl/p-halophenyl)imidazole-4-carbonitrile compounds had been developed by introducing an iodo atom at the C-5 position of the imidazole ring of 5-amino-1-(phenyl/p-halophenyl)imidazole-4-carbonitrile compounds. Specifically, 5-iodo-1-(4-iodophenyl)imidazole-4-carbonitrile compound had shown double Sonogashira coupling reactions with two differently substituted iodine along with the formation of two other compounds where an unusual coupling product with self-aggregation property was obtained. In other cases, monocoupling had been observed together with another compound where iodine atom present at C5 position of imidazole was replaced by hydrogen atom.