Amphiphilic star-block copolymers and supramolecular transformation of nanogel-like micelles to nanovesicles

Amphiphilic star-block copolymers based on poly(3-hydroxybutyrate) with adamantyl end-functionalization were synthesized via anionic ring-opening polymerization and alkyne-azide "Click Chemistry" coupling. In aqueous medium, the copolymers self-assembled into nanogel-like large compound micelles, and transformed into vesicular nanostructures under the direction of host-guest interaction between the adamantyl end and dimethyl-β-cyclodextrin.     

A phthalocyanine dendrimer capable of forming spherical micelles

A novel and intrinsically spherical micelle has been prepared by utilizing a silicon phthalocyanine ((WG3)SiPc) that has a thin hydrophobic alkyl chain and a bulky hydrophilic poly(aryl ether) dendrimer with terminal carboxyl groups, as its two axial ligands. Gel-permeation chromatography and cryo-transmission electron microscopic experiments indicate that (WG3)SiPcs self-assemble to form a spherical micelle at very low concentrations in aqueous solution. Depending on the pH of the aqueous phase, (WG3)SiPc shuttles between aqueous and organic phases. In the presence of hydrophobic molecules, this transfer is accompanied by the inclusion of these (guest) molecules, indicating that the micelle acts as a molecular capsule with a nanospace surrounded by functional phthalocyanine planes.     

Amphiphilic Janus micelles with polystyrene and poly(methacrylic acid) hemispheres

We describe the synthesis and the solution properties of Janus micelles containing a polybutadiene (PB) core and a compartmentalized corona consisting of a poly(methacrylic acid) (PMAA) and a polystyrene (PS) hemisphere. The Janus micelles were obtained via cross-linking the middle block of a microphase-separated PS-block-PB-block-PMMA triblock copolymer in the bulk state, followed by alkaline hydrolysis of the poly(methyl methacrylate) (PMMA) ester groups. Results of fluorescence correlation spectroscopy, field flow fractionation, light scattering, cryogenic transmission electron microscopy, scanning electron microscopy, and scanning force microscopy indicate that above a critical aggregation concentration of about 0.03 g/L spherical supermicelles are formed from about 30 PS-PMAA micelles in aqueous solution in the presence of NaCl. These supermicelles have radii of 40-60 nm, significantly increasing on ionization (pH >6). In addition, very large spherical objects are observed with radii of 100-250 nm.     

Attempts to generate a homocycloheptatrienylidene

Attempts to generate homocyclooctatetraene by dehydrohalogenation of 8-chlorobicyclo [5.1.0] octadiene led to cyclooctatetraene, styrene and heptafulvene.     

Evolution of multicompartment micelles to mixed corona micelles using solvent mixtures

Miktoarm star triblock copolymers mu-[poly(ethylethylene)][poly(ethylene oxide)][poly(perfluoropropylene oxide)] self-assemble in dilute aqueous solution to give multicompartment micelles with the cores consisting of discrete poly(ethylethylene) and poly(perfluoropropylene oxide) domains. Tetrahydrofuran is a selective solvent for both the poly(ethylethylene) and poly(ethylene oxide) blocks, and thus in tetrahydrofuran mixed corona micelles are favored with poly(perfluoropropylene oxide) cores. The introduction of tetrahydrofuran into water induces an evolution from multicompartment micelles to mixed corona [poly(ethylethylene) + poly(ethylene oxide)] micelles, as verified by dynamic light scattering and nuclear magnetic resonance spectroscopy. A mixed solvent containing 60 wt % tetrahydrofuran corresponds to the transition point, as verified by analysis of a poly(ethylethylene)-poly(ethylene oxide) diblock copolymer in the same solvent mixtures. Furthermore, cryogenic transmission electron microscopy suggests that, as the poly(ethylethylene) block transitions from the core to the corona, the micelle morphologies evolve from disks to oblate ellipsoid micelles (with some vesicles), with worms and spheres evident at intermediate compositions.     

Amphiphilic polyethylenes leading to surfactant-free thermoresponsive nanoparticles

Linear copolymers of ethylene and acrylic acid (PEAA) were prepared by catalytic polymerization of ethylene and tert-butyl acrylate followed by hydrolysis of the ester groups. The copolymers contained COOH groups inserted into the crystalline unit cell with formation of intramolecular hydrogen-bonds, as established on the basis of differential scanning calorimetry (DSC), Fourier-transform infrared spectroscopy (FTIR), and X-ray diffraction (XRD) studies. A solvent-exchange protocol, with no added surfactant, converted a solution in tetrahydrofuran of a PEAA sample containing 12 mol % of acrylic acid (AA) into a colloidally stable aqueous suspension of nanoparticles. Transmission electron microscopy (TEM), dynamic light scattering (DLS), and high sensitivity differential scanning calorimetry (HS-DSC) were used to characterize the nanoparticles. They are single crystals of elongated shape with a polar radius of 49 nm (σ = 15 nm) and an equatorial radius of 9 nm (σ = 3 nm) stabilized in aqueous media via carboxylate groups located preferentially on the particle/water interface. The PEAA (AA: 12 mol %) nanoparticles dispersed in aqueous media exhibited a remarkable reversible thermoresponsive behavior upon heating/cooling from 25 to 80 °C.     

Disulfide proteinoid micelles responsive to reduction

Abstract

Proteinoid composed of aspartic acid (Asp) and Leucine (Leu) (Prot(Asp-Leu)) and of Asp, Leu, and dithiopropionic acid (DTPA) (Prot(Asp-Leu-DTPA)) were prepared by melt-condensation method. ¹H NMR spectroscopy confirmed the successful synthesis of the proteinoids. The air/water interfacial tension of Prot(Asp-Leu-DTPA) solution increased when dithiothreitol (DTT, a reducing agent) was in the solution, possibly due to the breakdown of the disulfide bond of the proteinoid. On transmission electron micrograph, the proteinoid micelles were round and the diameter was less than 200?nm. Sulfur signal was found in the energy-dispersive X-ray spectrum of Prot(Asp-Leu-DTPA) micelle, indicating that the disulfide compound (i.e., DTPA) was successfully included in the proteinoid. As the pH value increased, the mean hydrodynamic diameter of the proteinoid micelle increased. The release degree of doxorubicin (DOX) loaded in Prot(Asp-Leu-DTPA) micelle was relatively low (3.5%–5.8%) and it was not affected by a reducing agent (i.e., DTT), possibly because of electrostatic attraction between DOX and the proteinoid. DTT had a significant effect on the release degree of amaranth (a negatively charged dye) loaded in Prot(Asp-Leu-DTPA) micelle. Prot(Asp-Leu-DTPA) has disulfide bonds so it can be broken into thiol proteinoids via DTT-caused reduction, giving rise to the micellar shell loosening and the promoted release.     

Stop-flow lithography to generate cell-laden microgel particles

Encapsulating cells within hydrogels is important for generating three-dimensional (3D) tissue constructs for drug delivery and tissue engineering. This paper describes, for the first time, the fabrication of large numbers of cell-laden microgel particles using a continuous microfluidic process called stop-flow lithography (SFL). Prepolymer solution containing cells was flowed through a microfluidic device and arrays of individual particles were repeatedly defined using pulses of UV light through a transparency mask. Unlike photolithography, SFL can be used to synthesize microgel particles continuously while maintaining control over particle size, shape and anisotropy. Therefore, SFL may become a useful tool for generating cell-laden microgels for various biomedical applications.     

Mild route to generate gaseous metal anions

Gaseous metal anions such as Na(-), K(-), Cs(-), and Ag(-) can be generated at ambient temperatures by the collision-induced dissociation of the anions of several dicarboxylic acid salts, including oxalate, maleate, fumarate, succinate, and glutamate salts. The formation of gaseous metal anions in this way is unprecedented because the metal is initially present in its cationic form. The mild process described here could facilitate novel applications of metal anions as selective reagents for gas-phase ion-molecule and ion-ion reactions. Ab initio calculations were used to describe the dissociation process for anions of the oxalate salts. The formation of alkalides occurs via production of a metal-carbon dioxide anion intermediate with a bidentate three-center two-electron bond to the metal. The metal atom acquires a partial negative charge in the intermediate structure.     

The application of the thermodynamic theory of ideal multi component micelles to ionic micelles

Summary The thermodynamic theory of ideal multi component micelles is applied to solutions of a single ionic surfactant plus electrolyte with common counterion. It is assumed that the activity coefficients of all micellar species are equal, that counterions can be regarded as bound or free and that non surface active simili-ions are absent from the micelles. Expressions are presented for the free energy, enthalpy and volume changes on micellisation, for the dependence of the latter two on counterion activity and for the individual contribution of surfactant ions and counterions to them. The dependence of the micellar degree of dissociation on counterion and micellar activities is also discussed. The use of an apparent degree of dissociation to incorporate all deviations from ideal behaviour is criticised.

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Zusammenfassung Es wird die thermodynamische Theorie der idealen mehrgliedrigen Mizellen auf L?sungen von einem einzigen Tensid plus Elektrolyt mit gemeinsamem Gegenion angewandt. Angenommen wird, da? die Aktivit?tskoeffizienten aller Mizellenarten gleich sind, da? die Gegenionen als gebundene oder freie betrachtet werden k?nnen und da? nicht-oberfl?chenaktive Similiionen (mizellengleiche Ladung) von den Mizellen abwesend sind. Es werden Gleichungen für freie Energie, Enthalpie und Volumen?nderungen bei Mizellisierung, sowie für die Abh?ngigkeit der zwei letzteren von der Gegenionaktivit?t wie auch für die Einzelbeitr?ge der Tensidionen und Gegenionen dazu eingeführt. Die Abh?ngigkeit des Dissoziationsgrades der Mizellen von Gegenionen- und Mizellenaktivit?ten wird auch diskutiert. Die Anwendung eines scheinbaren Dissoziationsgrades, um alle Abweichungen vom idealen Verhalten einzuschlie?en, wird bestritten.

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Algorithm to generate reaction pathways for computer-assisted elucidation

An algorithm is introduced that can generate reaction-pathway hypotheses for computer-assisted elucidation. A key aspect of the algorithm is its ability to conjecture reaction intermediates and products that are not input to the algorithm. The formal basis for the conjecture is stoichiometry, i.e., species variables are used in the construction of a pathway, and their molecular formulas are inferred when sufficient stoichiometric constraint is placed on the variables. These conjectured species have a degree of plausibility when the algorithm is used systematically to search for the simplest pathways consistent with given experimental evidence. The MECHEM system for computer-assisted elucidation under development by the author adapts this algorithm to generate initial pathway hypotheses from experimental data. © 1992 by John Wiley & Sons, Inc.     

Method to generate surfaces with desired roughness parameters

A surface engineering method based on the electrostatic deposition of microparticles and dry etching is described and shown to be able to independently tune both amplitude and spatial roughness parameters of the final surface. Statistical models were developed to connect process variables to the amplitude parameters (center line average and root-mean-square) and a spatial parameter (autocorrelation length) of the final surfaces. Process variables include particle coverage, which affects both amplitude and spatial roughness parameters, particle size, which affects only spatial parameters, and etch depth, which affects only amplitude parameters. Correlations between experimental data and model predictions are discussed.     

A skewed-momenta method to efficiently generate conformational-transition trajectories

We present a novel computational method, the skewed-momenta method (Skew'M), which applies a bias to the Maxwell distribution of initial momenta used to generate ensembles of trajectories. As a result, conformational transitions are accentuated and kinetic properties are calculated more effectively. The connection to the related puddle jumping method is discussed. A reweighting scheme permits the exact calculation of kinetic properties. Applications are presented for the rapid calculation of rate constants for molecular isomerization, and for the efficient reconstruction of free-energy profiles using a straightforward modification of the Jarzynski identity.     

Nickel-catalyzed selective defluorination to generate partially fluorinated biaryls

A Ni-catalyzed, chemoselective cross-coupling reaction of polyfluoroarenes under mild reaction conditions is reported. A variety of fluorine-containing biaryls are synthesized in good-to-excellent yields. A wide range of substitution patterns and functional groups are tolerated.     

Connecting small ligands to generate large tubular metal-organic architectures

The new metal-organic framework materials, ZnF(Am₂TAZ)·solvents and ZnF(TAZ)·solvents (Am₂TAZ=3,5-diamino-1,2,4-triazole, TAZ=1,2,4-triazole), have been synthesized solvothermally and structurally characterized by either Rietveld refinement from powder XRD data or by single crystal X-ray diffraction. The three-dimensional structures of the compounds display open-ended, tubular channels, which are constituted of covalently bonded hexanuclear metallamacrocycles (Zn₆F₆(ligand)₆). The tubular channels are subsequently covalently joined into a honeycomb-like hexagonal array to generate the three-dimensional porous framework. In the case of ZnF(Am₂TAZ)·solvents, hydrophilic -NH₂ groups point into the channels, effectively reducing their inner diameter relative to ZnF(TAZ)·solvents. The present compounds are isostructural to one another and to the previously reported ZnF(AmTAZ)·solvents (AmTAZ=3-amino-1,2,4-triazole), illustrative of the fact that the internal size and chemical properties of the framework may be altered by modification of the small, heterocyclic ligand. In addition to demonstrating the ability to modify the basic framework, ZnF(TAZ)·solvents and ZnF(Am₂TAZ)·solvents are two of the most thermally stable coordination frameworks known to date.     

From fibers to micelles using point-mutated amphiphilic peptides

Biocompatible, self-assembled nanostructures are attracting ever more attention, in particular in aqueous media for biomedical applications. Here, we present the successful, solid-phase peptide synthesis (SPPS) and characterization of short amino acid sequences with amphiphilic character with the aim of gaining insight into their self-assembled, supramolecular structures. The peptide design includes three parts: (a) a charged lysine part, (b) an acetylated lysine part, and (c) a constant hydrophobic rodlike helix, based on gramicidin A (gA). By stepwise replacement of free lysine (K) with acetylated lysine (X) we generated a library of a total of 10 peptides, Ac-X(8)-gA and K(m)X(8-m)-gA (m ranging from 0 to 8). By using point mutations, we adjusted the degree of acetylation (DA) and thus the overall amphiphilicity of the peptides, which led to a change in the secondary structure in the aqueous environment from a β-sheet to an α-helix. This transition generated a significant change in the morphology of the self-assembled structures from fibers to micelles. Two different regions were observed for the conformation of the hydrophilic part of the peptide: one region, a β-sheet-like secondary structure, inducing fiber formation (high DA), the other an α-helical-like secondary structure, generating micelle formation (moderate and low DA). The micellar structures depended on the degree of acetylation, which influenced their critical micelle concentration (cmc). These morphology regions were determined by a combination of circular dichroism, dynamic light scattering, surface tension, and transmission electron microscopy, which allowed us to correlate the generated supramolecular architectures with the fine changes obtained by means of the point mutation strategy.     

Negative adsorption due to electrostatic exclusion of micelles

Interactions of surfactants with solid substrates are important in the controlling of processes such as flotation, coating, flocculation and sedimentation. These interactions usually lead to adsorption on solids, but can also result in an exclusion of the reagents with dire consequences. In this work electrostatic exclusion of negatively charged dodecylbenzene sulfonate micelles from quartz/water, Bio-Sil/water and alumina/water interfaces has been investigated as a function of pH and ionic strength. Measurable negative adsorption of these surfactants from similarly charged solid/liquid interface was observed in the micellar region. In the case of porous samples with large surface area, comparison of pore size with the micelle size is necessary to avoid any erroneous conclusions regarding the role of electrostatic exclusion in a given system. A theoretical model for the electrostatic exclusion of micelles is developed and used to calculate the adsorption of negatively charged dodecylbenzene sulfonate on negatively charged quartz (pH 7), silica (Bio-Sil A, pH 3) and alumina (pH 11) in the micellar concentration region. The micellar exclusion values calculated using the model are in excellent agreement with the experimental results.     

Approach to peptide decorated micelles via RAFT polymerization

Pyridyldisulfide (PDS) functionalized telechelic polymers of oligo(ethyleneglycol) acrylate (PEG‐A) and their amphiphilic triblock copolymers with styrene (St) were synthesized directly by reversible addition‐fragmentation chain transfer (RAFT) polymerization using a new bifunctional RAFT agent, S,S‐bis[α,α′‐dimethyl‐α″‐(2‐pyridyl disulfide) ethyl acetate] trithiocarbonate (BDPET). The homopolymerization of PEG‐A was found to be well controlled using BDPET (PDI < 1.2). The ABA triblock copolymers poly(PEG‐A)‐b‐poly(St)‐b‐poly(PEG‐A) with narrow molecular weight distribution (PDI < 1.25) were synthesized using poly(PEG‐A) as a macro‐RAFT agent. UV‐vis spectroscopic analysis revealed that 85 mol % of poly(PEG‐A) and 78 mol % of poly(PEG‐A)‐b‐poly(St)‐b‐poly(PEG‐A) retained PDS end group functionality. Micelles were observed to form from poly(PEG‐A)‐b‐poly(St)‐b‐poly(PEG‐A). The presence of PDS groups within the micelle corona was evidenced by UV‐vis spectroscopy and fluorescence spectroscopy. The PDS groups within the corona were then used to functionalize the micelles with a thiol group bearing model peptide, reduced glutathione, and a thiol modified fluorophore, rhodamine B, under mild reaction conditions. UV‐vis and fluorescence spectrocopies revealed that approximately 80% PDS groups from the amphiphilic copolymer were tethered within the micelle coronas and accessible to glutathione and fluorophore attachment. © 2008 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 47: 899–912, 2009     

Terminal vanadium-neopentylidyne complexes and intramolecular cross-metathesis reactions to generate azametalacyclohexatrienes

Four-coordinate vanadium complexes containing a terminal neopentylidyne functionality have been prepared by two consecutive alpha-hydrogen abstraction reactions both of which were induced by one-electron oxidations. Among these vanadium-alkylidyne complexes are the neutral and the cation (Nacnac)VCtBu(OTf) and [(Nacnac)VCtBu(THF)]+, respectively (Nacnac- = [Ar]NC(CH3)CHC(CH3)N[Ar], Ar = 2,6-(CHMe2)2C6H3). The vanadium-alkylidynes have been characterized by 1H, 13C, 51V NMR spectroscopy and single-crystal X-ray diffraction and are consistent with a short VC bond. These alkylidynes were found to transform to azametalacyclohexatriene systems via an intramolecular cross-metathesis reaction. Kinetic studies of the transformation of (Nacnac)VCtBu(OTf) in C7D8 reveal the formation of the azametalacyclohexatriene to be independent of solvent (toluene vs THF) and the reaction to be first order in vanadium (k = 3.30(5) x 10-5 s-1 at 80 degrees C, with activation parameters DeltaH= 25.4(3) kcal/mol, DeltaS = -6(3) cal/molK). High-level DFT calculations on the full model suggest an intramolecular mechanism invoking only one transition state. The overall thermodynamic driving force for the reaction (DeltaG) in solution phase was estimated to be -21.3 kcal/mol.