Molecular Amphiphiles Research Articles

Design features for optimization of tetrapyrrole macrocycles as antimicrobial and anticancer photosensitizers.

Photodynamic therapy (PDT) uses non-toxic dyes called photosensitizers (PS) and harmless visible light that combine to form highly toxic reactive oxygen species that kill cells. Originally, a cancer therapy, PDT, now includes applications for infections. The most widely studied PS are tetrapyrrole macrocycles including porphyrins, chlorins, bacteriochlorins, and phthalocyanines. The present review covers the design features in PS that can work together to maximize the PDT activity for various disease targets. Photophysical and photochemical properties include the wavelength and size of the long-wavelength absorption peak (for good light penetration into tissue), the triplet quantum yield and lifetime, and the propensity to undergo type I (electron transfer) or type II (energy transfer) photochemical mechanisms. The central metal in the tetrapyrrole macrocycle has a strong influence on the PDT activity. Hydrophobicity and charge are important factors that govern interactions with various types of cells (cancer and microbial) in vitro and the pharmacokinetics and biodistribution in vivo. Hydrophobic structures tend to be water insoluble and require a drug delivery vehicle for maximal activity. Molecular asymmetry and amphiphilicity are also important for high activity. In vivo some structures possess the ability to selectively accumulate in tumors and to localize in the tumor microvasculature producing vascular shutdown after illumination.

Solvent Induced Morphological Evolution of Cholesterol Based Glucose Tailored Amphiphiles: Transformation from Vesicles to Nanoribbons.

Supramolecular self-assembly of low molecular mass amphiphiles is of topical interest with the urge to achieve precise control over the formation of various self-aggregated structures. Particularly, fabrication of multifarious nanostructures from single molecular backbone would be highly advantageous for task specific applications of the self-aggregates. To this end, the present study reports the solvent triggered evolution of hierarchical self-assembled structures of cholesterol based glucose appended amphiphiles and the pathway of structural transition. The amphiphiles formed bilayered vesicles in water and gels in different organic solvents. In DMSO-water solvent mixture, it showed gradual transition in the morphology of self-aggregates from vesicle-to-fiber and intermediate morphologies depending on the solvent compositions. Microscopic and spectroscopic investigations showed that morphological transformation took place through fusion, elongation and twisting of self-aggregates owing to the reorganization of the amphiphiles (H-type to J-type) in varied solvent polarity. Moreover, sheetlike molecular organization originating from hydrogen bonding and solvophobic interaction played a vital role in the formation of nanoribbons that led to the formation of gel fibril network. This study endows a new strategy to develop solvent induced multistructured self-aggregates from a single molecular scaffold, unraveling the route of forming hierarchical self-assembly.

Clickable Janus Particles.

Janus particles are colloidal analogues of molecular amphiphiles that can self-assemble to form diverse suprastructures, exhibit motility under appropriate catalytic reactions, and strongly adsorb to fluid-fluid interfaces to stabilize multiphasic fluid mixtures. The chemistry of Janus particles is the fundamental parameter that controls their behavior and utility as colloid surfactants in bulk solution and at fluid interfaces. To enable their widespread utilization, scalable methods that allow for the synthesis of Janus particles with diverse chemical compositions and shapes are highly desirable. Here, we develop clickable Janus particles that can be modified through thiol-yne click reactions with commercially available thiols. Janus particles are modified to be amphiphilic by introducing either carboxyl, hydroxyl, or amine moieties. We also demonstrate that regulating the extent of the modification can be used to control the particle morphology, and thus the type of emulsion stabilized, as well as to fabricate composite Janus particles through sequential click reactions. Modifying Janus particles through thiol-yne click chemistry provides a fast-reacting, scalable synthesis method for the fabrication of diverse Janus particles.

Cooperation of Amphiphilicity and Crystallization for Regulating the Self-Assembly of Poly(ethylene glycol)-block-poly(lactic acid) Copolymers

Tuning the amphiphilicity of block copolymers has been extensively exploited to manipulate the morphological transition of aggregates. The introduction of crystallizable moieties into the amphiphilic copolymers also offers increasing possibilities for regulating self-assembled structures. In this work, we demonstrate a detailed investigation of the self-assembly behavior of amphiphilic poly(ethylene glycol)-block-poly(l-lactic acid) (PEG-b-PLLA) diblock copolymers with the assistance of a common solvent in aqueous solution. With a given length of the PEG block, the molecular weight of the PLA block has great effect on the morphologies of self-assembled nanoaggregates as a result of varying molecular amphiphilicity and polymer crystallization. Common solvents including N,N-dimethylformamide, dioxane, and tetrahydrofuran involved in the early stage of self-assembly led to the change in chain configuration, which further influences the self-assembly of block copolymers. This study expanded the scope of PLA-based copolymers and proposed a possible mechanism of the sphere-to-lozenge and platelet-to-cylinder morphological transitions.

Functional foldamers that target bacterial membranes: The effect of charge, amphiphilicity and conformation

By varying the molecular charge, shape and amphiphilicity of a series of conformationally distinct diarylureas it is possible to control the levels of phospholipid membrane lysis using membranes composed of bacterial lipid extracts. From the data obtained, it appears as though the lysis activity observed is not due to charge, conformation or amphiphilicity in isolation, but that surface aggregation, H-bonding and other factors may also play a part. The work provides evidence that this class of foldamer possesses potential for optimisation into new antibacterial agents.

Strong Physical Hydrogels from Fibrillar Supramolecular Assemblies of Poly(ethylene glycol) Functionalized Hexaphenylbenzenes

Gel formation without chemical cross-links requires strong physical bonds, as observed in diverse molecular and macromolecular systems or supramolecular assemblies above a critical concentration. Here, we present a new molecular amphiphile of propeller-like hexaphenylbenzene derivative bearing two short poly(ethylene glycol) (PEG) chains which forms reversible physical gels comprising long (∼2.2 μm) bundles of hydrogel fibrils in coexistence with spherical micelles. Combination of topological (entanglement-like) interactions between the fibers and specific hydrophobic interactions due to the helicity of the PEG chains is proposed to account for the hydrogelation in the semidilute regime. The present supramolecular hydrogels, which are based on small molecules, exhibit extraordinary properties with an exceptionally strong dependence of the shear modulus on concentration, akin to the behavior of ultrahigh molecular weight cellulose-based fibers.

Photodynamic inactivation of Escherichia coli with cationic meso-tetraarylporphyrins – The charge number and charge distribution effects

The alarming level of antibiotic resistance in common pathogenic bacteria requires alternative methods for their control. In recent years, the photodynamic inactivation of microorganisms gained increased attention as an alternative to antibiotics in order to control bacterial diseases and to prevent the spreading of multiresistant bacteria. It has been shown that porphyrin derivatives, mainly those bearing positive charges, are excellent photosensitizers in photodynamic inactivation. In this study it was evaluated how the charge of the photosensitizer influences, per se, the inactivation of Escherichia coli. For that purpose, five cationic porphyrins (1a–5a) with identical meso substituent groups were used. The results show that singlet oxygen production, charge number, charge distribution, aggregation behaviour and molecular amphiphilicity are all important features that contribute to the photodynamic inactivation efficiency of the photosensitizer.

Amphiphilic Nanoparticles Control the Growth and Stability of Lipid Bilayers with Open Edges.

Molecular amphiphiles self-assemble in polar media to form ordered structures such as micelles and vesicles essential to a broad range of industrial and biological processes. Some of these architectures such as bilayer sheets, helical ribbons, and hollow tubules are potentially useful but inherently unstable owing to the presence of open edges that expose the hydrophobic bilayer core. Here, we describe a strategy to stabilize open bilayer structures using amphiphilic nanoparticle surfactants that present mixtures of hydrophilic and hydrophobic ligands on their surface. We observe that these particles bind selectively to the open edge of bilayer membranes to stabilize otherwise transient amphiphile assemblies. We show how such particles can precisely control the size of lipid tubules, how they can inhibit the formation of undesirable assemblies such as gallstone precursors, and how they can stabilize free-floating lipid microdiscs.

Self-Assembly of Polymer Tethered Molecular Nanoparticle Shape Amphiphiles in Selective Solvents

Well-defined giant molecular shape amphiphiles possessing a hydrophilic head with definite shape and size and a linear, hydrophobic polymeric tail with a length suitable to resemble the typical structure of a small-molecule surfactant were synthesized recently and were able to self-assemble into various morphologies in selective solvents. We investigated the self-assembly of shape amphiphiles consisting of a hydrophilic head and one or more hydrophobic tails using the dissipative particle dynamics (DPD) approach. The micellar morphology can transform from vesicles to worm-like cylinders and further to spheres by increasing the interaction parameter between the hydrophilic heads. The simulation results are in agreement with the experimental observations. Furthermore, the self-assembled aggregates exhibit a rich variety of morphological structures, such as spheres, vesicles, worm-like cylinders, pupa-like micelles, disk-like micelles, and segmented rod-like micelles, etc. We demonstrate how to create variou...

Introducing amphiphilicity to noble metal nanoclusters via phase-transfer driven ion-pairing reaction.

Amphiphilicity is a surface property that has yet to be explored for the noble metal nanoclusters (NCs). This article shows how amphiphilicity may be added to sub-2-nm metal NCs by patching hydrophilic NCs (e.g., Au25(MHA)18 NCs where MHA is 6-mercaptohexanoic acid) with hydrophobic cations (e.g., cetyltrimethylammonium ion, CTA(+)) to about half of a monolayer coverage. Specifically we demonstrate the preparation of amphiphilic Au25(MHA)18@xCTA NCs (x = 6-9 where x is the number of CTA(+) per NC) by the phase-transfer (PT) driven ion-paring reaction between CTA(+) and -COO(-) (derived from the deprotonation of the terminal carboxyl group of MHA). Due to the coexistence of flexible hydrophilic MHA and hydrophobic MHA···CTA ligands in comparable amounts on the NC surface, the Au25(MHA)18@xCTA NCs (x = 6-9) exhibit good amphiphilicity, which enabled them to dissolve in solvents with distinctly different polarities and to self-assemble like a molecular amphiphile. Consequently, the amphiphilic Au25(MHA)18@xCTA NCs (x = 6-9) could self-organize into stacked bilayers at the air-liquid interface, similar to the formation of lyotropic liquid crystalline phases by common surfactants. The good solubility and molecular-amphiphile-like self-assembly properties can significantly increase the utility of noble metal NCs in basic and applied research.

Thermal, light and pH triple stimulated changes in self-assembly of a novel small molecular weight amphiphile binary system

Temperature, light and pH induced morphological of C10AZOC2IMB and 4FS binary systems.

Self-assembly via microfluidics.

The self-assembly of amphiphilic building blocks has attracted extensive interest in myriad fields in recent years, due to their great potential in the nanoscale design of functional hybrid materials. Microfluidic techniques provide an intriguing method to control kinetic aspects of the self-assembly of molecular amphiphiles by the facile adjustment of the hydrodynamics of the fluids. Up to now, there have been several reports about one-step direct self-assembly of different building blocks with versatile and multi-shape products without templates, which demonstrated the advantages of microfluidics. These assemblies with different morphologies have great applications in various areas such as cancer therapy, micromotor fabrication, and controlled drug delivery.

Converting molecular monolayers into functional membranes.

Carbon nanomembranes are constructed from monolayers of molecular amphiphiles assembled on a water surface. The floating molecular film is cross-linked to form a mechanically stable nanomembrane. By varying the type of molecules, the surface area, and the exposure condition, the membrane's stiffness, thickness, and permeability can be tailored.

Supramolecular assembly of asymmetric self-neutralizing amphiphilic peptide wedges.

Mimicking the remarkable dynamic and multifunctional utility of biological nanofibers, such as microtubules, is a challenging and technologically attractive objective in synthetic supramolecular chemistry. Understanding the complex molecular interactions that govern the assembly of synthetic materials, such as peptides, is key to meeting this challenge. Using molecular dynamics simulations to guide molecular design, we explore here the self-assembly of structurally and functionally asymmetric wedge-shaped peptides. Supramolecular assembly into nanofiber gels or multilayered lamellar structures was determined by cooperative influences of hydrogen bonding, amphiphilicity (hydrophilic asymmetry), and the distribution of electrostatic charges on the aqueous self-assembly of asymmetric peptides. Molecular amphiphilicity and β-sheet forming capacity were both identified as necessary, but not independently sufficient, to form supramolecular nanofibers. Imbalances in positive and negative charges prevented nanofiber assembly, while the asymmetric distribution of balanced charges within a peptide is believed to affect peptide conformation and subsequent self-assembly into either nanofibers or lamellar structures. Insights into cooperative molecular interactions and the effects of molecular asymmetry on assembly may aid the development of next-generation supramolecular nanomaterial assemblies.

Shape-changing and amphiphilicity-reversing Janus particles with pH-responsive surfactant properties.

Janus particles are biphasic colloids that have two sides with distinct chemistry and wettability. Because of their amphiphilicity, Janus particles present a unique opportunity for stabilizing multiphasic fluid mixtures such as emulsions. Our work is motivated by one class of molecular amphiphiles that change their surfactant properties in response to environmental stimuli. Depending on the environmental conditions, these stimuli-responsive molecular amphiphiles are able to assemble into different structures, generate emulsions with different morphologies, and also induce phase inversion emulsification. We present a new synthesis method utilizing a combination of polymerization-induced phase separation and seeded emulsion polymerization, which allows for the bulk synthesis of highly uniform pH-responsive Janus particles that are able to completely reverse their surfactant properties in response to solution pH. One side of these Janus particles is rich in a hydrophobic monomer, styrene, whereas the other side is rich in a pH-sensitive hydrophilic repeating unit, acrylic acid. These Janus particles change their aggregation/dispersion behavior and also transform into different shapes in response to pH changes. Furthermore, we demonstrate that these Janus particles can stabilize different types of emulsions (oil-in-water and water-in-oil) and, more importantly, induce phase inversion of emulsions in response to changes in solution pH. The pH-responsive aggregation/dispersion behavior of these Janus particles also allows us to tune the interactions between oil-in-water emulsion droplets without inducing destabilization; that is, emulsion drops with attractive or repulsive interactions can be generated by changing the pH of the aqueous phase. Our study presents a new class of colloidal materials that will further widen the functionality and properties of Janus particles as dynamically tunable solid surfactants.

Entropy-Driven Pattern Formation of Hybrid Vesicular Assemblies Made from Molecular and Nanoparticle Amphiphiles

Although an analogy has been drawn between them, organic molecular amphiphiles (MAMs) and inorganic nanoparticle (NP) amphiphiles (NPAMs) are significantly different in dimension, geometry, and composition as well as their assembly behavior. Their concurrent assembly can synergetically combine the inherent properties of both building blocks, thus leading to new hybrid materials with increasing complexity and functionality. Here we present a new strategy to fabricate hybrid vesicles with well-defined shape, morphology, and surface pattern by coassembling MAMs of block copolymers (BCPs) and NPAMs comprising inorganic NPs tethered with amphiphilic BCPs. The assembly of binary mixtures generated unique hybrid Janus-like vesicles with different shapes, patchy vesicles, and heterogeneous vesicles. Our experimental and computational studies indicate that the different nanostructures arise from the delicate interplay between the dimension mismatch of the two types of amphiphiles, the entanglement of polymer chains, and the mobility of NPAMs. In addition, the entropic attraction between NPAMs plays a dominant role in controlling the lateral phase separation of the two types of amphiphiles in the membranes. The ability to utilize multiple distinct amphiphiles to construct discrete assemblies represents a promising step in the self-assembly of structurally complex functional materials.

Biaxial mesophase behavior of amphiphilic anisometric colloids: a simulation study.

The phase behavior of amphiphilic anisometric particles is explored using Monte Carlo simulations. The particles are composed of two incompatible laterally attached units: a spherocylinder and a spheroplatelet. A liquid crystalline phase polymorphism is obtained including biaxial nematic, (quasi long range biaxial) calamitic smectic-A, biaxial lamellar and columnar phases. The simulation results demonstrate intriguing phase transitions such as nematic-nematic, discotic nematic to (quasi long range biaxial) calamitic smectic-A, biaxial nematic to uniaxial calamitic smectic-A, and isotropic or discotic nematic to biaxial lamellar phases that possess nematic ordering within the layers. These findings are rationalized in terms of molecular geometry and amphiphilicity of different molecular units. The molecular model can be used as a tool for the prediction of the complex phase behavior that is relevant to liquid crystalline colloids.

Self-Assembly of Polymer Brush-Functionalized Inorganic Nanoparticles: From Hairy Balls to Smart Molecular Mimics

New opportunities for complex and controllable self-organization of inorganic nanoparticles (e.g., quantum dots, plasmonic or magnetic nanoparticles) are provided when the stabilizing organic layer at the nanoparticle surface consists of a polymer brush of densely grafted chains. We highlight recent advances in the synthesis and self-assembly of these unique building blocks, termed polymer brush-functionalized nanoparticles (PBNPs). We show how the field has progressed from PBNPs with isotropic, single-component brushes showing limited self-assembly behavior to PBNPs with anisotropic brushes showing directional interactions and complex self-organization. We further discuss how PBNPs with isotropic multicomponent brushes, either mixed brushes or grafted block copolymers, can also exhibit the complex self-organization of molecular amphiphiles via rearrangements within the brush enabled by conformational flexibility. Through numerous examples, we show how established principles of polymer science and surface...

Exactly Defined Half-Stemmed Polymer Lamellar Crystals with Precisely Controlled Defects’ Locations

We describe highly unconventional situations in which the polymer chain ends remain trapped in and are located in the middle of the lamellar crystal core as defects. Such structures are observed in giant molecular shape amphiphiles constructed by a polyhedral silsesquioxane (POSS) nanoparticle tethered with a poly(ethylene oxide) (PEO) tail. The cross-sectional area of the POSS located on the PEO lamellar surfaces imposes that the crystalline, chain-folded PEO tails generate a surface area that is at least comparable to the POSS requirements. Metastable PEO crystal structures with 1.5, 2, and 2.5 stem numbers have been observed with different thermodynamic stabilities.

Trimethylamine N-Oxide (TMAO) and tert-Butyl Alcohol (TBA) at Hydrophobic Interfaces: Insights from Molecular Dynamics Simulations

TMAO, a potent osmolyte, and TBA, a denaturant, have similar molecular architecture but somewhat different chemistry. We employ extensive molecular dynamics simulations to quantify their behavior at vapor-water and octane-water interfaces. We show that interfacial structure-density and orientation-and their dependence on solution concentration are markedly different for the two molecules. TMAO molecules are moderately surface active and adopt orientations with their N-O vector approximately parallel to the aqueous interface. That is, not all methyl groups of TMAO at the interface point away from the water phase. In contrast, TBA molecules act as molecular amphiphiles, are highly surface active, and, at low concentrations, adopt orientations with their methyl groups pointing away and the C-O vector pointing directly into water. The behavior of TMAO at aqueous interfaces is only weakly dependent on its solution concentration, whereas that of TBA depends strongly on concentration. We show that this concentration dependence arises from their different hydrogen bonding capabilities-TMAO can only accept hydrogen bonds from water, whereas TBA can accept (donate) hydrogen bonds from (to) water or other TBA molecules. The ability to self-associate, particularly visible in TBA molecules in the interfacial layer, allows them to sample a broad range of orientations at higher concentrations. In light of the role of TMAO and TBA in biomolecular stability, our results provide a reference with which to compare their behavior near biological interfaces. Also, given the ubiquity of aqueous interfaces in biology, chemistry, and technology, our results may be useful in the design of interfacially active small molecules with the aim to control their orientations and interactions.