Amphiphilic Oligomers Research Articles

Physicochemical control of solvation and molecular assembly of charged amphiphilic oligomers at air-aqueous interfaces

Hypothesis: Understanding the rules that control the assembly of nanostructured soft materials at interfaces is central to many applications. We hypothesize that electrolytes can be used to alter the hydration shell of amphiphilic oligomers at the air-aqueous interface of Langmuir films, thereby providing a means to control the formation of emergent nanostructures.Experiments: Three representative salts – (NaF, NaCl, NaSCN) were studied for mediating the self-assembly of oligodimethylsiloxane methylimidazolium (ODMS-MIM+) amphiphiles in Langmuir films. The effects of the different salts on the nanostructure assembly of these films were probed using vibrational sum frequency generation (SFG) spectroscopy and Langmuir trough techniques. Experimental data were supported by atomistic molecular dynamic simulations.Findings: Langmuir trough surface pressure – area isotherms suggested a surprising effect on oligomer assembly, whereby the presence of anions affects the stability of the interfacial layer irrespective of their surface propensities. In contrast, SFG results implied a strong anion effect that parallels the surface activity of anions. These seemingly contradictory trends are explained by anion driven tail dehydration resulting in increasingly heterogeneous systems with entangled ODMS tails and appreciable anion penetration into the complex interfacial layer comprised of headgroups, tails, and interfacial water molecules. These findings provide physical and chemical insight for tuning a wide range of interfacial assemblies.

Insulin Tregopil: An Ultra-Fast Oral Recombinant Human Insulin Analog: Preclinical and Clinical Development in Diabetes Mellitus.

Insulin therapy is indispensable for achieving glycemic control in all patients with type 1 diabetes mellitus and manypatients with type 2 diabetes mellitus. Insulin injections are associated with negative connotations in patients owing to administration discomfort and adverse effects such as hypoglycemia and weight gain. Insulin administered orally can overcome these limitations by providing a convenient and effective mode of delivery with a potentially lower risk of hypoglycemia. Oral insulin mimics the physiologic process of insulin secretion, absorption into the portal circulation, and subsequent peripheral delivery, unlike the subcutaneous route that results in peripheral hyperinsulinemia. Insulin tregopil (IN-105), a new generation human recombinant insulin, methoxy (polyethylene glycol) hexanoyl human recombinant insulin, is developed by Biocon as an ultra-fast onset short-acting oral insulin analog. This recombinant oral insulin is a single short-chain amphiphilic oligomer modified with the covalent attachment of methoxy-triethylene-glycol-propionyl moiety at Lys-β29-amino group of the B-chain via an amide linkage. Sodium caprate, an excipient in the insulin tregopil formulation, is a permeation enhancer that increases its absorption through the gastrointestinal tract. Also, meal composition has been shown to non-significantly affect its absorption. Several global randomized, controlled clinical trials have been conducted in type 1 and type 2 diabetes patients towards the clinical development of insulin tregopil. The formulation shows post-prandial glucose control that ismore effective than placebo throughout the meal period; however, compared withan active comparator insulin aspart, the post-prandial control ismore effective mainly in the early post-meal period. It shows a good safety profile with a lower incidence of clinically significant hypoglycemia. This review covers the overall clinical development of insulin tregopil establishing it as an ultra-fast onset, short-acting oral insulin analog for optimizing post-prandial glucose.

Antifouling polysulfone membranes with an amphiphilic triblock additive

Triblock amphiphilic oligomers polydiol terephthalate polyvinylpyrrolidone (PDT-(PVP)2) were synthesized as the additive for the preparation of antifouling polysulfone (PSf) membranes. The influences of oligomer contents on membrane properties such as wettability, morphology, porosity, antifouling, etc were investigated. Among the synthesized oligomers, the one with the medium hydrophobic chain length at a blending percentage of 1.5% exhibited better filtration/antifouling performances. The contact angle of the blend membrane can reach as low as 60.3°. The water permeation of the blend membrane was increased from 85.1 L/(m2h) for the pristine PSf membrane to a maximum of 210.0 L/(m2h) for the blend membrane. All three oligomer blended membranes can achieve a bovine serum albumin rejection ratio of over 95.0%. The minimum amount of protein adsorbed on the blend membrane is ∼9.73 μg/cm2. Moreover, the flux recovery ratio of the blend membranes is remarkably higher than that of the pristine membrane. Surface atomic content and water contact angle measurements suggested that the amphiphilic oligomers migrated to the surface of the membrane during membrane formation process, and microstructure photographs of the membranes indicated that the amphiphilic oligomer accelerated the pore formation speed, all of which correlated well with the filtration and antifouling results. Moreover, there is no obvious deviation of water contact angles on the membrane surfaces before and after treatment in boiling water, which means that the amphiphilic oligomers were hardly washed off from the membrane, thus, the as-prepared amphiphilic PDT-(PVP)2 oligomers are able to exhibit sustainable antifouling ability.

Alternatingly Amphiphilic Antimicrobial Oligoguanidines: Structure–Property Relationship and Usage as the Coating Material with Unprecedented Hemocompatibility

With the emergence of antibiotic resistance in recent years, the combat against bacteria is becoming more difficult and critical in human healthcare. In addition to the development of new chemical entities and derivatives of antibiotics and disinfectants, the antimicrobial surface is recognized as a potential way to prevent healthcare-associated infections, particularly those caused by medical devices such as implants and various catheters. However, traditional ways of engineering antimicrobial surfaces using coated metal nanostructures or blended-in antibiotics inevitably face the problem of metal ion or antibiotic leakage, leading to surface deactivation, toxicity, and antibiotic resistance. A new strategy developed in recent years involves the use of coated cationic antimicrobial polymers, which serve as resistance-resistant, surface-anchored antibacterial agents, but they also usually come with hemolytic activity resulting from their membrane-disrupting-type mechanism of action. In this report, we show that the combinatorial approach can be highly useful for the selection of alternatingly amphiphilic oligomers, which are essentially molecular nanorods as revealed by molecular dynamic simulations. The combinatorial process allowed the structure–property relationship of these molecular nanorods to be revealed and yielded oligoguanidine hit with high antimicrobial activity, fast killing kinetics, and extremely low hemolytic activity through assay screening. We demonstrate that the covalent conjugation of such a prescreened oligoguanidine nanorod to glass slides or polycaprolactone films could produce antimicrobial surfaces with excellent performance. A catheter prototype made using such a modified polycaprolactone film could transport bacteria-contaminated liquid, efficiently removing all bacteria without causing lysis of red blood cells.

Ion Pairing and Molecular Orientation at Liquid/Liquid Interfaces: Self-Assembly and Function.

Molecular orientation plays a pivotal role in defining the functionality and chemistry of interfaces, yet accurate measurements probing this important feature are few, due, in part, to technical and analytical limitations in extracting information from molecular monolayers. For example, buried liquid/liquid interfaces, where a complex and poorly understood balance of inter- and intramolecular interactions impart structural constraints that facilitate the formation of supramolecular assemblies capable of new functions, are difficult to probe experimentally. Here, we use vibrational sum-frequency generation spectroscopy, numerical polarization analysis, and atomistic molecular dynamics simulations to probe molecular orientations at buried oil/aqueous interfaces decorated with amphiphilic oligomers. We show that the orientation of self-assembled oligomers changes upon the addition of salts in the aqueous phase. The evolution of these structures can be described by competitive ion effects in the aqueous phase altering the orientations of the tails extending into the oil phase. These specific anionic effects occur via interfacial ion pairing and associated changes in interfacial solvation and hydrogen-bonding networks. These findings provide more quantitative insight into orientational changes encountered during self-assembly and pave the way for the design of functional interfaces for chemical separations, neuromorphic computing applications, and related biomimetic systems.

Synthesis, Self-Assembly and In Vitro Cellular Uptake Kinetics of Nanosized Drug Carriers Based on Aggregates of Amphiphilic Oligomers of N-Vinyl-2-pyrrolidone.

Development of nanocarrier-based drug delivery systems is a major breakthrough in pharmacology, promising targeted delivery and reduction in drug toxicity. On the cellular level, encapsulation of a drug substantially affects the endocytic processes due to nanocarrier–membrane interaction. In this study we synthesized and characterized nanocarriers assembled from amphiphilic oligomers of N-vinyl-2-pyrrolidone with a terminal thiooctadecyl group (PVP-OD). It was found that the dissolution free energy of PVP-OD depends linearly on the molecular mass of its hydrophilic part up to = 2 × 104, leading to an exponential dependence of critical aggregation concentration (CAC) on the molar mass. A model hydrophobic compound (DiI dye) was loaded into the nanocarriers and exhibited slow release into the aqueous phase on a scale of 18 h. Cellular uptake of the loaded nanocarriers and that of free DiI were compared in vitro using glioblastoma (U87) and fibroblast (CRL2429) cells. While the uptake of both DiI/PVP-OD nanocarriers and free DiI was inhibited by dynasore, indicating a dynamin-dependent endocytic pathway as a major mechanism, a decrease in the uptake rate of free DiI was observed in the presence of wortmannin. This suggests that while macropinocytosis plays a role in the uptake of low-molecular components, this pathway might be circumvented by incorporation of DiI into nanocarriers.

Toward Chemotactic Supramolecular Nanoparticles: From Autonomous Surface Motion Following Specific Chemical Gradients to Multivalency-Controlled Disassembly.

Nature designs chemotactic supramolecular structures that can selectively bind specific groups present on surfaces, autonomously scan them moving along density gradients, and react once a critical concentration is encountered. Since such properties are key in many biological functions, these also offer inspirations for designing artificial systems capable of similar bioinspired autonomous behaviors. One approach is to use soft molecular units that self-assemble in an aqueous solution generating nanoparticles (NPs) that display specific chemical groups on their surface, enabling multivalent interactions with complementarily functionalized surfaces. However, a first challenge is to explore the behavior of these assemblies at sufficiently high-resolution to gain insights on the molecular factors controlling their behaviors. Here, by coupling coarse-grained molecular models and advanced simulation approaches, we show that it is possible to study the (autonomous or driven) motion of self-assembled NPs on a receptor-grafted surface at submolecular resolution. As an example, we focus on self-assembled NPs composed of facially amphiphilic oligomers. We observe how tuning the multivalent interactions between the NP and the surface allows to control of the NP binding, its diffusion along chemical surface gradients, and ultimately, the NP reactivity at determined surface group densities. In silico experiments provide physical–chemical insights on key molecular features in the self-assembling units which determine the dynamic behavior and fate of the NPs on the surface: from adhesion, to diffusion, and disassembly. This offers a privileged point of view into the chemotactic properties of supramolecular assemblies, improving our knowledge on how to design new types of materials with bioinspired autonomous behaviors.

An Aromatic Oligomer Micelle: Large Enthalpic Stabilization and Selective Oligothiophene Uptake

AbstractAn aromatic oligomer micelle, featuring both high stability and high uptake ability, was quantitatively formed in water from amphiphilic oligomers, composed of three bent polyaromatic amphiphiles connected alternately by two hydrophilic chains. The well‐defined micelle, with a diameter of ca. 2 nm, remains intact even under highly diluted conditions (ca. 3 μM) and at elevated temperature (>130 °C), due to the polyaromatic chelate effect. The thermodynamic studies reveal that large enthalpic gain (ΔH=−110 kJ mol−1) is the key for the micelle formation. The oligomer micelle selectively encapsulates unsubstituted oligothiophenes (≥4‐mer) to a high degree and the resultant, aqueous host‐guest complexes display unusual emission derived from the multiply stacked oligomers. Furthermore, facile uptake and release of unsubstituted polythiophenes can be achieved using the oligomer micelle.

An Aromatic Oligomer Micelle: Large Enthalpic Stabilization and Selective Oligothiophene Uptake.

An aromatic oligomer micelle, featuring both high stability and high uptake ability, was quantitatively formed in water from amphiphilic oligomers, composed of three bent polyaromatic amphiphiles connected alternately by two hydrophilic chains. The well-defined micelle, with a diameter of ca. 2 nm, remains intact even under highly diluted conditions (ca. 3 μM) and at elevated temperature (>130 °C), due to the polyaromatic chelate effect. The thermodynamic studies reveal that large enthalpic gain (ΔH=-110 kJ mol-1 ) is the key for the micelle formation. The oligomer micelle selectively encapsulates unsubstituted oligothiophenes (≥4-mer) to a high degree and the resultant, aqueous host-guest complexes display unusual emission derived from the multiply stacked oligomers. Furthermore, facile uptake and release of unsubstituted polythiophenes can be achieved using the oligomer micelle.

Emulsion polymerization using three types of RAFT prepared well-defined cationic polymeric stabilizers based on 2-dimethylaminoethyl methacrylate (DMAEMA): a comparative study

Three types of well-defined stabilizers, based on 2-dimethylaminoethyl methacrylate (DMAEMA), including poly(2-dimethylaminoethyl methacrylate) (PDMAEMA), poly(2-dimethylaminoethyl methacrylate)-block-poly(methyl methacrylate) (PDMAEMA-b-PMMA), and PDMAEMA-co-PMMA, were synthesized through reversible addition-fragmentation chain transfer (RAFT) solution polymerization and used as well-defined cationic stabilizers in emulsion (co)polymerization of styrene and/or methyl methacrylate (MMA). Because of different characteristics of MMA and styrene, using varying ratios of these monomer as well as using different structures of stabilizers allowed us to better understanding of stabilizers’ behavior during polymerization course. The results showed that PDMAEMA-b-PMMA was more robust against changes in monomer composition, meaning less fluctuations in particle size distribution and kinetics plots. Also, more than 85% monomer conversion was reached and the resulting polymer particles, ranging in diameter from 75 to ~135 nm. Using PDMAEMA-b-PMMA and adding only 5 mol% MMA as a comonomer in emulsion polymerization of styrene resulted in producing highly uniform particles with size polydispersity of (0.04), as confirmed by TEM and DLS. This narrow size polydispersity was attributed to generation of more positively charged amphiphilic oligomers at early stages of polymerization and thus, faster nucleation.

Stimuli-Responsive Supramolecular Chirality Switching and Nanoassembly Constructed by n-Shaped Amphiphilic Molecules in Aqueous Solution.

Self-assembled nanomaterials composed of amphiphilic oligomers with functional groups have been applied in the fields of biomimetic chemistry and on-demand delivery systems. Herein, we report the assembly behavior and unique properties of an emergent n-shaped rod-coil molecule containing an azobenzene (AZO) group upon application of an external stimulus (thermal, UV light). The n-shaped amphiphilic molecules comprising an aromatic segment based on anthracene, phenyl linked with azobenzene groups, and hydrophilic oligoether (chiral) segments self-assemble into large strip-like sheets and perforated-nanocage fragments in an aqueous environment, depending on the flexible oligoether chains. Interestingly, the nano-objects formed in aqueous solution undergo a morphological transition from sheets and nanocages to small one-dimensional nanofibers. These molecules exhibit reversible photo- and thermal-responsiveness, accompanied by a change in the supramolecular chirality caused by the conformational transitions of the rod backbone. The architecture of n-shaped amphiphilic molecules with a photosensitive group makes them ideal candidates for intelligent materials for applications in advanced materials science.

Smart supramolecular nanofibers and nanoribbons from uniform amphiphilic azobenzene oligomers.

A series of self-assembled 1D nanostructures, including straight and helix nanofibers, nanoribbons, and nanobelts, were fabricated from uniform amphiphilic azobenzene oligomers with tunable molecular weight and side chain functionality, promoted by multiple and cooperative supramolecular interactions. Additionally, the morphological transformation of the nanofibers was achieved during the photoisomerization process.

Supramolecular nanoparticles self-assembled from reduction-responsive cabazitaxel prodrugs for effective cancer therapy.

Using hydrophobic cabazitaxel as a target anticancer drug, we show that the conjugation of oligo(ethylene glycol)-oligolactide (OEG-OLA) via a self-immolative linkage induces the self-assembly of the resulting prodrug into injectable nanoparticles. The nanoparticles release chemically unmodified cabazitaxel after endocytosis in cancer cells. With the optimal conjugate, the nanotherapy not only potently induces tumor regression but also has a higher safety margin in animals than the free drug administered in its clinical formulation. Our studies highlight the design rationale that attaching a short amphiphilic oligomer to a toxic drug can convert it to a self-deliverable and safe nanotherapy.

Pressure-Sensitive Adhesive with Controllable Adhesion for Fabrication of Ultrathin Soft Devices.

As the interest in foldable smartphones recently launched onto the market shifts toward the next generation of flexible electronics, the development of ultrathin devices is gaining considerable attention. The strain formed on the surfaces of film-based devices approximates the film thickness divided by twice the radius of curvature; therefore, the use of an ultrathin substrate is the key for the development of next generation foldable devices. However, the stiffness of ultrathin films is extremely low; thus, it cannot be easily used directly as a substrate for device fabrication. Therefore, these films generally undergo device manufacturing processes while being attached to a rigid substrate such as glass and are peeled from the rigid substrate after the process is finished. Thus, the initial adhesion of the adhesive used to fix the film to the temporary substrate should be strong, and after the process is completed, the adhesion must be lessened to enable soft peeling. In this study, we succeeded in developing a novel pressure-sensitive adhesive (PSA) whose adhesive strength can be severely reduced by water treatment. Accordingly, considering that amphiphilic oligomers promote water absorption through hydrogen bonding to water, amphiphilic oligomers were mixed with an acrylic polymer to prepare the water-responsive PSA (wr-PSA). The adhesion strength of the wr-PSA in the early stage, which reached 382(±22) N/m, dramatically dropped to 9(±2) N/m after a water immersion test. Using the wr-PSA, a 1.4 μm-thick polyethylene terephthalate film coated with Ag nanowires was softly peeled off from the glass after being immersed in warm water. In addition, the adhesion reduced by the immersion in water was recovered again when the water absorbed by the adhesive was dried. This implies that the developed adhesive can be reusable.

Water-responsive pressure-sensitive adhesive with reversibly changeable adhesion for fabrication of stretchable devices

Owing to the extremely low stiffness of elastomeric materials commonly used as substrates of stretchable devices, fabrication of stretchable devices is usually performed with an elastic film attached to a rigid temporary substrate. The problem is that the stress applied to the elastic film during peeling induces a severely large deformation of the film, resulting in performance degradation of the devices formed thereon. To address this, a water-induced, softly peelable, pressure-sensitive adhesive (wisp-PSA) was developed by synthesizing a new amphiphilic oligomer and mixing it with acryl-based PSA. As amphiphilic oligomers facilitate more water uptake in the adhesive layer, hydrogen bonding between the polymers and water molecules weakens the hydrogen bonding in the polymers and to the substrate, resulting in decrease in adhesion. The initial adhesion strength of the wisp-PSA, which reached about 152 N/m, was dramatically dropped to about 8 N/m after immersing in water. Through the use of wisp-PSA, polyurethane film with Ag nanowires formed thereon could be safely peeled, without damage, from the glass after immersion in warm water. Furthermore, the adhesion strength lowered by the water treatment was almost restored when the water absorbed by the oligomer was dried, revealing that the developed wisp-PSA is reusable.

Synthesis of peroxid-containing hetero-chain amphiphilic oligomers their colloid-chemical properties

New surface-active oligomers were synthesized with the alternative placement of hydrophilic and lipophilic blocks based on substituted peroxide-containing oxetanes and polyesters of higher dicarboxylic acids and polyethylene glycols of different molecular weights. By acylation of peroxide-containing oxetane with dichloroanhydride decane and dodecanedioic acids, the

Manipulating Hybrid Nanostructures by the Cooperative Assembly of Amphiphilic Oligomers and Triblock Janus Nanoparticles.

The cooperative assembly of nanoparticles and amphiphilic molecules has emerged as an appealing strategy for fabricating hybrid nanomaterials for a wide range of potential applications. However, it is challenging to precisely manipulate hybrid nanostructures. In this study, extensive dissipative particle dynamics simulations are carried out to investigate the cooperative assembly of amphiphilic oligomers and triblock Janus nanoparticles with different hydrophobic-hydrophilic patches. Three different hybrid nanostructures (networks, disks, and vesicles) are observed from the simulations. The structural characteristics and kinetic pathways are analyzed in detail. We reveal that the hydrophobic-hydrophilic patches in the triblock Janus nanoparticles significantly affect the arrangement of amphiphiles and nanoparticles, as well as the orientational degree of freedom between nanoparticles; therefore, the triblock Janus nanoparticles can function as a robust structure-directing agent to regulate the spatial organization of nanoparticles in networks, the curvature of disks, and the size of vesicles. This study demonstrates the cooperative assembly can serve as an efficient platform for the engineering of hybrid nanomaterials with tailored nanostructures.

A Novel Freeze-Drying-Free Strategy to Fabricate a Biobased Tough Aerogel for Separation of Oil/Water Mixtures

Renewable biobased porous aerogels with excellent biodegradability have versatile applications in oil/water separation, catalysis, and tissue engineering. However, processing of the porous matrix is challenging due to the high energy consumption and low efficiency from the fabrication procedures, such as freeze-drying or critical-drying of the hydrogel, which need to be improved. In the present study, natural amphiphilic oligomer shellac secreted by the lac Kerriar Lacca insect was employed to fabricate the porous template, which could self-assemble into a continuous rigid network with a hydrophobic core. Because of the hydrophobic core, the hydrated shellac network could be directly dried without collapse by the ambient air. The air-drying shellac aerogel presented a great mechanical property. The silane-coating treatment converted this shellac aerogel into a hydrophobic material that absorbed various organic solvents and oils. Also, this silane-coated shellac aerogel also could remove organic solvent or oil from the bottom or surface of the water. Notably, the saturable aerogel rapidly degraded in pH 14 and released the solvent absorbed by this matrix. This porous and hydrophobic matrix also could be applied as a filter that could connect with a vacuum pump to assemble a device for continuous collecting of oil from water. It also has great potential to be employed as a high-efficiency strategy to treat large scale oil spill issues. A new porous template composed of natural resin secreted by the insect was fabricated, and the whole fabrication process was green, low-cost, and energy saving. The surface of this template could be modified further to effectuate other processes, such as catalysis, heavy metal absorption, and tissue proliferation.

Structural Analysis on Gold Nanoparticles Protected by Sugar-Based Amphiphilic Oligomers

Structural Analysis on Gold Nanoparticles Protected by Sugar-Based Amphiphilic Oligomers

Insight into the Mechanisms Driving the Self-Assembly of Functional Interfaces: Moving from Lipids to Charged Amphiphilic Oligomers.

Polymer-stabilized liquid/liquid interfaces are an important and growing class of bioinspired materials that combine the structural and functional capabilities of advanced synthetic materials with naturally evolved biophysical systems. These platforms have the potential to serve as selective membranes for chemical separations and molecular sequencers and to even mimic neuromorphic computing elements. Despite the diversity in function, basic insight into the assembly of well-defined amphiphilic polymers to form functional structures remains elusive, which hinders the continued development of these technologies. In this work, we provide new mechanistic insight into the assembly of an amphiphilic polymer-stabilized oil/aqueous interface, in which the headgroups consist of positively charged methylimidazolium ionic liquids, and the tails are short, monodisperse oligodimethylsiloxanes covalently attached to the headgroups. We demonstrate using vibrational sum frequency generation spectroscopy and pendant drop tensiometery that the composition of the bulk aqueous phase, particularly the ionic strength, dictates the kinetics and structures of the amphiphiles in the organic phase as they decorate the interface. These results show that H-bonding and electrostatic interactions taking place in the aqueous phase bias the grafted oligomer conformations that are adopted in the neighboring oil phase. The kinetics of self-assembly were ionic strength dependent and found to be surprisingly slow, being composed of distinct regimes where molecules adsorb and reorient on relatively fast time scales, but where conformational sampling and frustrated packing takes place over longer time scales. These results set the stage for understanding related chemical phenomena of bioinspired materials in diverse technological and fundamental scientific fields and provide a solid physical foundation on which to design new functional interfaces.