Tyrosine Side-Chain Functionalities at Distinct Positions Determine the Chirooptical Properties and Supramolecular Structures of Pentameric Oligothiophenes

Control over the photophysical properties and molecular organization of π-conjugated oligothiophenes is essential to their use in organic electronics. Herein we synthesized and characterized a variety of anionic pentameric oligothiophenes with different substitution patterns of L- or D-tyrosine at distinct positions along the thiophene backbone. Spectroscopic, microscopic, and theoretical studies of L- or D-tyrosine substituted pentameric oligothiophene conjugates revealed the formation of optically active π-stacked self-assembled aggregates under acid conditions. The distinct photophysical characteristics, as well as the supramolecular structures of the assemblies, were highly influenced by the positioning of the L- or D-tyrosine moieties along the thiophene backbone. Overall, the obtained results clearly demonstrate how fundamental changes in the position of the enantiomeric side-chain functionalities greatly affect the optical properties as well as the architecture of the self-assembled supramolecular structures.     

Curvature modulates the self-assembly of amphiphilic molecules

In this work, we used lattice Monte Carlo simulations and theoretical model calculations to show how the self-assembly of adsorbed amphiphilic molecules is affected by the local curvature of solid surfaces. It is found that, beyond a critical curvature value, solid surface geometry governs the spatial ordering of aggregates and may induce the morphological transitions. The simulation results show how the curvature of solid surfaces modulates the distribution of aggregates: the anisotropy in local curvature along and perpendicular to the cylindrical surfaces tends to generate orientationally ordered cylindrical micelles. To account for the morphological transitions induced by the local curvature of solid surfaces, we constructed a theoretical model which includes the Helfrich bending energy, the deformation energy of aggregates induced by solid surfaces, and the adsorption energy. The model calculations indicate that on highly curved solid surfaces the bending energy for bilayer structure sharply increases with surface curvature, which in turn induces the morphological transition from bilayer to cylindrical structure. Our results suggest that the local curvature provides a means of controlling the spatial organization of amphiphilic molecules.     

The Structural Basis for Optimal Performance of Oligothiophene‐Based Fluorescent Amyloid Ligands: Conformational Flexibility is Essential for Spectral Assignment of a Diversity of Protein Aggregates

Protein misfolding diseases are characterized by deposition of protein aggregates, and optical ligands for molecular characterization of these disease‐associated structures are important for understanding their potential role in the pathogenesis of the disease. Luminescent conjugated oligothiophenes (LCOs) have proven useful for optical identification of a broader subset of disease‐associated protein aggregates than conventional ligands, such as thioflavin T and Congo red. Herein, the molecular requirements for achieving LCOs able to detect nonthioflavinophilic Aβ aggregates or non‐congophilic prion aggregates, as well as spectrally discriminate Aβ and tau aggregates, were investigated. An anionic pentameric LCO was subjected to chemical engineering by: 1) replacing thiophene units with selenophene or phenylene moieties, or 2) alternating the anionic substituents along the thiophene backbone. In addition, two asymmetric tetrameric ligands were generated. Overall, the results from this study identified conformational freedom and extended conjugation of the conjugated backbone as crucial determinants for obtaining superior thiophene‐based optical ligands for sensitive detection and spectral assignment of disease‐associated protein aggregates.     

Evaluation of Isoprene Chain Extension from PEO Macromolecular Chain Transfer Agents for the Preparation of Dual, Invertible Block Copolymer Nanoassemblies

Two RAFT-capable PEO macro-CTAs, 2 and 5 kDa, were prepared and used for the polymerization of isoprene which yielded well-defined block copolymers of varied lengths and compositions. GPC analysis of the PEO macro-CTAs and block copolymers showed remaining unreacted PEO macro-CTA. Mathematical deconvolution of the GPC chromatograms allowed for the estimation of the blocking efficiency, about 50% for the 5 kDa PEO macro-CTA and 64% for the 2 kDa CTA. Self assembly of the block copolymers in both water and decane was investigated and the resulting regular and inverse assemblies, respectively, were analyzed with DLS, AFM, and TEM to ascertain their dimensions and properties. Assembly of PEO-b-PIp block copolymers in aqueous solution resulted in well-defined micelles of varying sizes while the assembly in hydrophobic, organic solvent resulted in the formation of different morphologies including large aggregates and well-defined cylindrical and spherical structures.     

Structures of micelles formed by synthetic alkyl glycosides with unsaturated alkyl chains

Three new alkyl glycosides with similar molecular structures (oleyl and oleoyl alkyl chains and various head groups: disaccharide, trisaccharide and disaccharide with an additional amidoethoxy spacer) were synthesized and their supramolecular structure in aqueous solution was investigated. Small angle neutron scattering, surface tension measurement and the contact preparation method were applied to get molecular structure-property relationships. Although the chemical structures differ only in small details, their CMC values, lyotropic phase behaviour, surface area per surfactant molecule in the micelle and at the liquid-air interface, and the size and shape of the micelles are very different. We have found three different types of aggregates: spherical, cylindrical and polymer-like micelles in dilute solutions.     

Bilayers connected by threadlike micelles in amphiphilic mixtures: a self-consistent field theory study

Binary mixtures of amphiphiles in solution can self-assemble into a wide range of structures when the two species individually form aggregates of different curvatures. A specific example of this is seen in solutions of lipid mixtures where the two species form lamellar structures and spherical micelles, respectively. Here, vesicles connected by threadlike micelles can form in a narrow concentration range of the sphere-forming lipid. We present a study of these structures based on self-consistent field theory (SCFT), a coarse-grained model of amphiphiles. First, we show that the addition of sphere-forming lipid to a solution of lamella-former can lower the free energy of cylindrical, threadlike micelles and hence encourage their formation. Next, we demonstrate the coupling between composition and curvature; specifically, that increasing the concentration of sphere-former in a system of two bilayers connected by a thread leads to a transfer of amphiphile to the thread. We further show that the two species are segregated within the structure, with the concentration of sphere-former being significantly higher in the thread. Finally, the addition of larger amounts of sphere-former is found to destabilize the junctions linking the bilayers to the cylindrical micelle, leading to a breakdown of the connected structures. The degree of segregation of the amphiphiles and the amount of sphere-former required to destabilize the junctions is shown to be sensitive to the length of the hydrophilic block of the sphere-forming amphiphiles.     

Molecular dynamics simulations of polyelectrolyte brushes: from single chains to bundles of chains

Using molecular dynamics simulations in combination with scaling analysis, we have studied the effects of the solvent quality and the strength of the electrostatic interactions on the conformations of spherical polyelectrolyte brushes in salt-free solutions. The spherical polyelectrolyte brush could be in one of four conformations: (1) a star-like conformation, (2) a "star of bundles" conformation in which the polyelectrolyte chains self-assemble into pinned cylindrical micelles, (3) a micelle-like conformation with a dense core and charged corona, or (4) a conformation in which there is a thin polymeric layer uniformly covering the particle surface. These different brush conformations appear as a result of the fine interplay between electrostatic and monomer-monomer interactions. The brush thickness depends nonmonotonically on the value of the Bjerrum length. This dependence of the brush thickness is due to counterion condensation inside the brush volume. We have also established that bundle formation in poor solvent conditions for the polymer backbone can also occur in a planar polyelectrolyte brush. In this case, the grafted polyelectrolyte chains form hemispherical aggregates at low polymer grafting densities, cylindrical aggregates at an intermediate range of the grafting densities, and vertically oriented ribbon-like aggregates at high grafting densities.     

Aggregate morphologies of amphiphilic graft copolymers in dilute solution studied by self-consistent field theory

Microstructures assembled by amphiphilic graft copolymers in a selective solvent (poor for the backbone chain and good for graft chains or poor for graft chains and good for the backbone chain) were investigated on the basis of a real-space algorithm of self-consistent field theory in two-dimensions. Circle-like micelles, line-like micelles, large compound micelles, and vesicles are obtained by tailoring the architectural parameters and interaction parameter between the graft blocks and solvents. The aggregate morphology stability regions of graft copolymers as functions of the position of first graft point and the number of branches are constructed. It is found that the architectural parameters play a remarkable role in the complex microstructure formation. The interaction between the graft blocks and solvents is also shown to exert an effect on the morphology stability regions. The distributions of the free end and inner blocks of the backbone are found to be different in various aggregate structures. For the circle-like micelles assembled by graft copolymers with a hydrophobic backbone and vesicles assembled by graft copolymers with a hydrophilic backbone, the free end and inner blocks segregate and localize in different parts of the aggregates depending on their length. However, with respect to the large compound micelles and vesicles assembled by graft copolymers with a hydrophobic backbone, the free end and inner blocks uniformly mix in the clusters.     

Synthesis of a library of oligothiophenes and their utilization as fluorescent ligands for spectral assignment of protein aggregates

Molecular probes for selective identification of protein aggregates are important to advance our understanding of the molecular pathogenesis underlying protein aggregation diseases. Here we report the chemical design of a library of anionic luminescent conjugated oligothiophenes (LCOs), which can be utilized as ligands for detection of protein aggregates. Certain molecular requirements were shown to be necessary for detecting (i) early non-thioflavinophilic protein assemblies of Aβ1-42 and insulin preceding the formation of amyloid fibrils and (ii) for obtaining distinct spectral signatures of the two main pathological hallmarks observed in human Alzheimer's diease brain tissue (Aβ plaques and neurofibrillary tangles). Our findings suggest that a superior anionic LCO-based ligand should have a backbone consisting of five to seven thiophene units and carboxyl groups extending the conjugated thiophene backbone. Such LCOs will be highly useful for studying the underlying molecular events of protein aggregation diseases and could also be utilized for the development of novel diagnostic tools for these diseases.     

Boltzmann distributions and slow relaxation in systems with spherical and cylindrical micelles

Equilibrium and nonequilibrium distributions of molecular aggregates in a solution of a nonionic surfactant are investigated at the total surfactant concentration above the second critical micelle concentration (CMC2). The investigation is not limited by the choice of a specific micellar model. Expressions for the direct and reverse fluxes of molecular aggregates over the potential humps of the aggregation work are derived. These aggregation work humps set up activation barriers for the formation of spherical and cylindrical micelles. With the aid of the expressions for molecular aggregate fluxes, a set of two kinetic equations of micellization is derived. This set, along with the material balance equation, describes the molecular mechanism of the slow relaxation of micellar solution above the CMC2. A realistic situation has been analyzed when the CMC2 exceeds the first critical micelle concentration, CMC1, by an order of magnitude, and the total surfactant concentration varies within the range lying markedly above the CMC2 but not by more than 2 orders of magnitude. For such conditions, an equation relating the parameters of the aggregation work of a cylindrical micelle to the observable ratio of the total surfactant concentration and the monomer concentration is found for an equilibrium solution. For the same conditions, but in the nonequilibrium state of materially isolated surfactant solution, a closed set of linearized relaxation equations for total concentrations of spherical and cylindrical micelles is derived. These equations determine the time development of two modes of slow relaxation in micellar solutions markedly above the CMC2. Solving the set of equations yields two rates and two times of slow relaxation.     

End-to-end coupling and network formation behavior of cylindrical block copolymer micelles with a crystalline polyferrocenylsilane core

Cylindrical block copolymer micelles with a crystalline poly(ferrocenyldimethylsilane) (PFDMS) core and a long corona-forming block are known to elongate through an epitaxial growth mechanism on addition of further PFDMS block copolymer unimers. We now report that addition of the semicrystalline homopolymer PFDMS(28) to monodisperse short (ca. 200 nm), cylindrical seed micelles of PFDMS block copolymers results in the formation of aggregated structures by end-to-end coupling to form micelle networks. The resulting aggregates were characterized by dynamic light scattering (DLS), transmission electron microscopy (TEM), and atomic force microscopy (AFM). In some cases, a core-thickening effect was also observed where the added homopolymer appeared to deposit and crystallize at the core-corona interface, which resulted in an increase of the width of the micelles within the networks. No evidence for aggregation was detected when the amorphous homopolymer poly(ferrocenylethylmethylsilane) (PFEMS(25)) was added to the cylindrical seed micelles whereas similar behavior to PFDMS(28) was noted for semicrystalline polyferrocenyldimethylgermane (PFDMG(30)). This suggested that the crystallinity of the added homopolymer is critical for subsequent end-to-end coupling and network formation to occur. We also explored the tendency of the cylindrical seed micelles to form aggregates by the addition of PI-b-PFDMS (PI = polyisoprene) block copolymers (block ratios 6:1, 3.8:1, 2:1, or 1:1), and striking differences were noted. The results ranged from typical micelle elongation, as reported in previous work, at high corona to core-forming block ratios (PI-b-PFDMS; 6:1) to predominantly end-to-end coupling at lower ratios (PI-b-PFDMS; 2:1, 1:1) to form long, essentially linear structures. The latter process, especially for the 2:1 block copolymer, led to much more controlled aggregate formation compared with that observed on addition of homopolymers.     

Study of the formation of dye-induced premicellar aggregates and its application to the determination of quaternary ammonium surfactants

Formation of dye-induced mixed premicellar aggregates from binary surfactant solutions is proposed for the determination of alkyltrimethylammonium surfactants at the muM level. The Coomassie Brilliant Blue G (CBBG) dye, negatively charged, induces the formation of cationic surfactant aggregates at concentrations far below the cmc. The role of CBBG in the formation of premicelles was studied by using pyrene as a fluorimetric probe. Formation of CBBG-cationic surfactant aggregates of well-defined stoichiometries that depend on the total surfactant concentration added is demonstrated. Also, the influence of analytical parameters affecting the concentration at which a given aggregate is formed was studied. Linear calibrations for alkyltrimethylammonium surfactants were obtained by using different cationic surfactants as titrants; therefore, the previously derived measurement parameter for mixed micelles is applicable to premicellar aggregates as well.     

Concentrations of Monomers and Cylindrical Micelles above the Second CMC

Based on thermodynamically substantiated linear dependence of the work of cylindrical micelle formation on the aggregation number within a wide range of aggregation numbers where the cylindrical micelles are accumulated in a surfactant solution, the second critical micellization concentration (CMC) is introduced as an overall surfactant concentration at which the ratio of the total amount of substance in cylindrical micelles to the amount of substance in monomers is equal to 0.1, i.e., it is already noticeable. It is shown that this ratio increases rather rapidly with a monomer concentration. The coefficient of the linear dependence of the work of cylindrical micelle formation on the aggregation number in the important practical situation where the ratios of the total concentration of cylindrical micelles and total amount of substance in these micelles to the monomer concentration are equal by the order of magnitude to 1 and 10⁵, respectively, while disc micelles and extended bilayers are still not appeared. In the same situation, the ratios of the total concentration of spherical micelles and total amount of substance in these micelles to the monomer concentration are equal by the order of magnitude to 1 and 10², respectively. The relationship between the overall surfactant concentration and monomer concentration is found. It is shown that the second CMC exceeds by two orders of magnitude the first CMC corresponding to the onset of the noticeable accumulation of surfactant in spherical micelles. The distribution of cylindrical micelles over the aggregation numbers is analyzed. It is demonstrated that, in agreement with the experiment, the distribution is almost uniform in the considerable part of the wide range of aggregation numbers and drops exponentially in the remaining (right-hand) part of this range. Experimental result is confirmed that the total concentration of cylindrical micelles, the mean value, and the mean statistical scatter of aggregation numbers in a cylindrical micelle is proportional to the square root of the overall surfactant concentration. The balance equation of surfactant amount in the vicinity of the final equilibrium state of a materially isolated solution is linearized. This linearization makes it possible to express the deviations of monomer and aggregate concentrations from their equilibrium values at the lower boundary of the region of the linear dependence of the work of cylindrical micelle formation on the aggregation numbers via the deviations of experimentally observed total concentrations of spherical and cylindrical micelles from their equilibrium values. The case of the solutions of such surfactants, for which spherical shape appeared to be unrealizable due to their molecular structure and packing conditions, is considered separately.     

Structure and dynamics of concentrated micellar solutions of sodium dodecyl sulfate

In micellar solutions of sodium dodecyl sulfate, as the concentration of surfactants increases, the spheroid shape of the micelles changes from almost spherical to ellipsoidal with increasing ratio of half-axes ratio, and further the transition to cylindrical micelles occurs. The micelles in an aqueous solution can directly contact (compact aggregates) or be separated from one another by layers of intermicellar medium (periodical colloid structures). In the latter case, the thickness of the layer can significantly exceed the micelle size, and then no mutual correlation in micelle arrangement is observed. According to the data of small-angle X-ray scattering, the relationship between the surfactant concentration and formation of “quasi-crystalline” micellar structure is nonlinear, which can be due to both micelle aggregation processes and nonuniformity of their structure. The possible influence of ordered micellar structures on the diffusion mobility of micelles is shown.     

Effect of mixing on the morphology of cylindrical micelles

Increasing the spontaneous curvature of an amphiphile can lead to a first-order morphology transition from threadlike micelles to a branched network. The two morphologies were linked to entropy-driven topological defects; networks are dominated by Y-junctions, while linear threadlike structures are dominated by spherical end-caps. In this paper we investigate the effect of mixing on the morphological transitions in nonionic amphiphilic systems. We find that mixed equilibrium structures are obtained within seconds; these mixed cylindrical structures display comparable numbers of end-caps and branch points, resulting in a novel 'short armed' branched (SAB) morphology. Quite surprisingly, the probability of either defect (end-caps or branch points) is independent of composition, so that neither a first-order nor a second-order morphological transition is observed. A possible explanation may be local demixing of the two amphiphilic components, which adds a degree of freedom and thus enables the formation of a unique morphology that cannot be obtained in single-component systems. We further find that within a relatively large composition range phase equilibrium exists between vesicles, SAB micelles, and spherical micelles.     

Supramolecular Packing Drives Morphological Transitions of Charged Surfactant Micelles

The shape and size of self-assembled structures upon local organization of their molecular building blocks are hard to predict in the presence of long-range interactions. Combining small-angle X-ray/neutron scattering data, theoretical modelling, and computer simulations, sodium dodecyl sulfate (SDS), over a broad range of concentrations and ionic strengths, was investigated. Computer simulations indicate that micellar shape changes are associated with different binding of the counterions. By employing a toy model based on point charges on a surface, and comparing it to experiments and simulations, it is demonstrated that the observed morphological changes are caused by symmetry breaking of the irreducible building blocks, with the formation of transient surfactant dimers mediated by the counterions that promote the stabilization of cylindrical instead of spherical micelles. The present model is of general applicability and can be extended to all systems controlled by the presence of mobile charges.     

Interfacial reactivity of block copolymers: understanding the amphiphile-to-hydrophile transition

Block copolymers offer an interesting platform to study chemically triggered transitions in self-assembled structures. We have previously reported the oxidative degradation of vesicles made of poly(propylene sulfide)-poly(ethylene glycol) (PPS-PEG) copolymers. Here we propose a mechanism for vesicle degradation deduced from copolymer conformational changes occurring at the air/water interface in a Langmuir trough together with a reactive subphase. The hydrophobic PPS block is converted into hydrophilic poly(propylene sulfoxide) and poly(propylene sulfone) by oxidation upon exposure to 1% aqueous H(2)O(2) subphase. As a result, a dramatic increase in area per molecule at constant surface pressure (Pi) was observed, followed by an apparent decrease (recorded as decrease in area at constant Pi) due to copolymer dissolution. For monolayers at the air/water surface, the large interfacial tensions present suppress increases in local curvature for alleviating the increased hydrophilicity of the copolymer chains. By contrast, vesicles can potentially rearrange molecules in their bilayers to accommodate a changing hydrophilic-lipophilic balance (HLB). Similar time scales for monolayer rearrangement and vesicle degradation imply a common copolymer chain solubilization mechanism, which in vesicles lead to an eventual transition to aggregates of higher curvature, such as cylindrical and spherical micelles. Subtle differences in response to the applied surface pressure for the diblock compared to the triblock suggest an effect of the different chain mobility.     

Molecular theory of surfactant micelles in aqueous solution

This paper presents an overview of recent theoretical work on the molecular theory of micelle formation. A primary emphasis is given to the role of computer simulation of condensed materials in understanding micelle structure and thermodynamics. Much of the detailed discussion focuses on recent Monte Carlo studies of a simple molecular model of micellar aggregates. For clarity of presentation, a compact, physical organization of micelle thermodynamic equilibrium ratios is advocated. This procedure provides a simple basis for physical reasoning about the molecular roles of attractive and repulsive forces in micellization thermodynamics. The molecularly coarse-grained micellar structural information available from current small angle neutron scattering (SANS) measurements is surveyed. The structural predictions of the reviewed Monte Carlo calculations are shown to be in good qualitative agreement with the SANS data. The Monte Carlo results indicate that micelles should be viewed as fluid aggregates with a low surface free energy relative to water-hydrocarbon interfaces. The computer experimental results suggest that dynamic surface and shape fluctuations should be considered in understanding micelle structure at a molecular level. Several instantaneous structures are graphically displayed to illustrate that these transitory structures could be qualitatively described as “dry” but irregularly shaped. Configurations drawn from Monte Carlo calculations on cylindrical and bilayer structures of infinite extent are used to illustrate the role of surface flexibility in these systems.     

Low-frequency dielectric relaxation in columnar hexagonal and micellar inverse cubic mesophases

Dielectric measurements on four diols showing columnar hexagonal and micellar cubic phases were carried out. Besides the known fast local reorientation in theGHz-range, a new absorption in theMHz region was detected. This mechanism was interpreted as a collective motion of the molecules inside the micelles or cylindrical aggregates. The absorption was also found in the isotropic phase. Based upon the interpretation given, the molecular aggregates should also exist in the isotropic state. The electrical conductivity strongly supports the classification as inverse phases.