Amphiphilic Ligands Research Articles

Dual‐Protected Metal Halide Perovskite Nanosheets with an Enhanced Set of Stabilities

AbstractApproaches to achieve stable perovskite nanocrystals (PNCs) of interest, in particular those with large structural anisotropy, through protective coating of the inorganic shell at a single‐nanocrystal (NC) level are comparatively few and limited in scope. Reported here is a robust amphiphilic‐diblock‐copolymer‐enabled strategy for crafting highly‐stable anisotropic CsPbBr3 nanosheets (NSs) by in situ formation of a uniform inorganic shell (1st shielding) that is intimately ligated with hydrophobic polymers (2nd shielding). The dual‐protected NSs display an array of remarkable stabilities (i.e., thermal, photostability, moisture, polar solvent, aliphatic amine, etc.) and find application in white‐light‐emitting diodes. In principle, by anchoring other multidentate amphiphilic polymer ligands on the surface of PNCs, followed by templated‐growth of shell materials of interest, a rich variety of dual‐shelled, multifunctional PNCs with markedly improved stabilities can be created for use in optics, optoelectronics, and sensory devices.

Amphiphilic Biaryl Monophosphine Ligands by Regioselective Sulfonation.

Amphiphilic ligands are valued for their ability to facilitate organometallic reactions in the presence of water. The regioselective sulfonation of a series of commercially available biaryl monophosphines to generate amphiphilic ligands is presented. In this one-step protocol, the temperature and addition of fuming sulfuric acid were carefully controlled to arrive at sulfonated biaryl monophosphine ligands in high yields with >95% regioselectivity without the need for chromatographic purification.

Hexagonal Microparticles from Hierarchical Self-Organization of Chiral Trigonal Pd3L6 Macrotetracycles

Construction of structurally complex architectures using inherently chiral, asymmetric, or multi-heterotopic ligands is a major challenge in metallosupramolecular chemistry. Moreover, the hierarchical self-organization of such complexes is unique. Here, we introduce a water-soluble, facially amphiphilic, amphoteric, chiral, asymmetric, and hetero-tritopic ligand derived from natural bile acid, ursodeoxycholic acid. We show that via the supramolecular transmetalation reaction, using nitrates of Cu(II) or Fe(III), and subsequently Pd(II), a superchiral Pd 3 L 6 complex can be obtained. Even though several possible constitutional isomers of Pd 3 L 6 could be formed, because of the ligand asymmetry and relative flexibility of carbamate-pyridyl moieties attached to the steroid scaffold, only a single product with C 3 rotational symmetry was obtained. Finally, we demonstrate that these amphiphilic complexes can self-organize into hexagonal microparticles in aqueous media. This finding may lead to the development of novel self-assembled metal-organic functional materials made of natural, abundant, and relatively inexpensive steroidal compounds. Asymmetric, amphiphilic, chiral, and hetero-tritopic ligand from bile acid Supramolecular transmetalation self-assembly leads to symmetric superchiral complex Complexes self-organize in aqueous environment into hexagonal microparticles Materials with high density of chiral centers and optical activity are prepared Jurček et al. report an amphiphilic bile-acid-based ligand (L) used for the preparation of large hollow metallosupramolecular complex Pd 3 L 6 , accomplished via a supramolecular transmetalation process. The complexes prepared can self-organize into hexagonal microparticles upon contact with water.

Mechanistic Insight into Lipid Binding to Yeast Niemann Pick Type C2 Protein.

Niemann Pick type C2 (NPC2) is a small sterol binding protein in the lumen of late endosomes and lysosomes. We showed recently that the yeast homologue of NPC2 together with its binding partner NCR1 mediates integration of ergosterol, the main sterol in yeast, into the vacuolar membrane. Here, we study the binding specificity and the molecular details of lipid binding to yeast NPC2. We find that NPC2 binds fluorescence- and spin-labeled analogues of phosphatidylcholine (PC), phosphatidylserine, phosphatidylinositol (PI), and sphingomyelin. Spectroscopic experiments show that NPC2 binds lipid monomers in solution but can also interact with lipid analogues in membranes. We further identify ergosterol, PC, and PI as endogenous NPC2 ligands. Using molecular dynamics simulations, we show that NPC2's binding pocket can adapt to the ligand shape and closes around bound ergosterol. Hydrophobic interactions stabilize the binding of ergosterol, but binding of phospholipids is additionally stabilized by electrostatic interactions at the mouth of the binding site. Our work identifies key residues that are important in stabilizing the binding of a phospholipid to yeast NPC2, thereby rationalizing future mutagenesis studies. Our results suggest that yeast NPC2 functions as a general "lipid solubilizer" and binds a variety of amphiphilic lipid ligands, possibly to prevent lipid micelle formation inside the vacuole.

Evaluation and optimization of mixed-micelle mediated cloud point extraction of nickel(II) from concentrated chloride medium with Triton X-114-amphiphilic Schiff bases

ABSTRACT The extraction properties of original mixed micellar systems, Triton X-114/N-alkylsalicylideneimine type amphiphilic Schiff bases, have been investigated for removal of nickel(II) from aqueous solutions. The acid-base behavior of chelating Schiff bases in aqueous micellar solution was first studied, and their acidity constants were determined. The phase diagram of Triton X-114/water micellar system was then established, The cloud point extraction of nickel(II) by mixed micelles Triton X-114/amphiphilic Schiff base ligand was studied in a concentrated chloride medium, as function of pH, extractant and surfactant concentrations, temperature and time. The stoichiometry of the extracted Ni(II)-complexes was finally determined.

Amphiphilic silver nanoclusters show active nano\u2013bio interaction with compelling antibacterial activity against multidrug-resistant bacteria

Multidrug resistance represents a growing threat to human beings, and alternative antimicrobial regimens to conventional antibiotic paradigms are being extensively searched to fight against multidrug-resistant bacteria (MDRB). Although the antimicrobial potency of silver nanomaterials (AgNMs) has been previously elaborated, their efficacy against MDRB still remains to be strengthened. Here, our data revealed that small-sized silver nanoclusters (AgNCs) are superior to conventional silver nanoparticles (AgNPs) as robust antimicrobials against multidrug-resistant (MDR) Pseudomonas aeruginosa (P. aeruginosa). The core structure and surface ligands of AgNCs are crucial for the outstanding antibacterial activity of AgNCs. On the one hand, due to the presence of amphiphilic ligands, AgNCs are relatively prone to associate with the cell membrane and partake in endocytosis with targeted bacterial cells. Molecular dynamics simulations also corroborated this finding. On the other hand, the nanocluster structure of AgNCs led to strong peroxidase-like activity associated with massive production of reactive oxygen species (ROS), which contributes to their overall bactericidal potency. These outstanding features of AgNCs result in elevated bacterial killing efficacy by impairing the cell wall/membrane, promoting oxidative stress and attenuating pivotal cellular processes, e.g., ATP synthesis. Notably, AgNCs manifested great efficacy in treating P. aeruginosa-generated pneumonia in mice and increased the survival of infected animals, as well as exhibited excellent biocompatibility. Taken together, the results of this study pinpoint the great promise of AgNCs as new alternative therapeutics against MDR P. aeruginosa.

Investigations on the unusual aggregation behaviour of tetra(2-ethyhexyl)diglycolamide in n-dodecane medium upon gamma irradiation

The limit of reverse micellar aggregation of amphiphilic ligands in n-dodecane medium, known as the third phase formation, is an undesirable event during the course of solvent extraction. The tetraalkyl diglycolamide (DGA) in n-dodecane (n-DD) is a promising solvent medium for the extraction of trivalent actinides from high-level nuclear waste, but it is susceptible to third phase formation. The DGAs in n-dodecane medium undergo a number of chemical transformations in organic phase, known as the radiolytic degradation products, when it was contacted with nuclear waste. While the effect of radiolytic degradation products on the solvent extraction behaviour of actinides was reasonably understood, the third phase formation and reverse micellar aggregation behaviour of the radiolytically degraded DGAs/n-DD has been not explored so far and unfamiliar to the solvent extraction community. To unravel the effect of radiolytic degradation on the aggregation behaviour(third phase formation) of DGAs in n-DD, the following categories of liquids comprising of (1) 0.2 M solution of tetra(2-ethylhexyl)diglycolamide (TEHDGA) present in n-DD, (2) TEHDGA alone, (3) n-dodecane alone, and (4) 0.2 M TEHDGA/n-DD in the presence of extracted nitric acid, were irradiated to a specified absorbed dose levels (10 kGy to 500 kGy) in a 60Co gamma irradiator. The irradiated liquids were made to a solution of 0.2 M TEHDGA in n-dodecane, if required, and the extraction behaviour of nitric acid in the irradiated organic phase was studied. The organic phase obtained after extraction was subjected to dynamic light scattering studies to explore the aggregation behaviour of TEHDGA in organic phase and compared with those obtained before extraction and irradiation. The results revealed that the formation of polar degradation products upon irradiation minimized the aggregation, and the production of higher homologs of n-paraffins enhanced aggregation. In reality, the formation of nitration and other polar radiolytic degradation products in organic phase, confirmed by FTIR spectroscopy, minimized the aggregation and therefore prevented the third phase formation to a significant extent in the present system.

Ultrahigh energy-density flexible dielectric films achieved by self-bundled polymer nanocluster in necklace-like arrangement

Flexible dielectric materials with ultrahigh energy density (Ue) is of critical importance to reduce the size of dielectric capacitors, which has recently drawn ever-increasing attention. Herein, different from the incorporation of traditional 1D/2D inorganic nanofiller into single/multi-layer polymer matrix, a multifunctional poly (p-phenylene terephthalamide) (PPTA)-based derivative fluxible polymer (f-PPTA) nanocluster is selected and introduced to typical ferroelectric poly (vinylidene fluoride) (PVDF) matrix. As a novel polymer-based nanofiller, the f-PPTA nanocluster consists of self-bundled parallel sulfonated PPTA skeleton and grafted with octadecylamine polyoxyethylene ether amphiphilic (PEGO) amine ligand through ionic interaction. In the multi-arm amphiphilic PEGO, one alkyl chain with the length of 15 carbon atoms provides similar hydrophobic nature to that of PVDF, which contributes to improving the interfacial compatibility between polymer nanocluster and matrix. Furthermore, the relatively short hydrophilic chain with the length of 8 carbon atoms induces a specific necklace-like arrangement of the f-PPTA nanoclusters in PVDF matrix during film fabrication spontaneously. Consequently, an ultrahigh Ue ~ 22.5 J•cm−3 of the dielectric film is acquired at 600 MV•m−1 electric field. This value is the highest reported so far among all the poly (vinylidene fluoride) (PVDF)-based dielectric nanocomposites to the best of our knowledge. In addition, the elongation at break of the film can be increased to 390%, which is over 9 times that of pure PVDF sample. This work provides a new route to PVDF-based polymer nanocomposites with ultrahigh Ue and highly stretchable performance.

Preparation of pH-Responsive Doxorubicin Nanocapsules by Combining High-gravity Antisolvent Precipitation with In-situ Polymerization for Intracellular Anticancer Drug Delivery

Owing to the low pH value in tumor and cancer cells, drug delivery systems based on pH-responsive polymer nanocarriers have been extensively explored for anticancer chemotherapy. Herein, we developed a pH-responsive doxorubicin(DOX) nanocapsule(named as DNanoCapsule) prepared by combining in-situ polymerization technique with high-gravity antisolvent precipitation technique through an amphiphilic polymerized surface ligand. DNanoCapsules show an obvious spherical core-shell structure with a single DOX nanoparticle encapsulated in the polymer layer. Dissolution rate studies prove that the DNanoCapsules have robust drug-release profiles under acidic environments due to the division of the pH-sensitive cross-linker, which triggers the collapse of the polymer layer. The in vitro investigations demonstrated that the DNanoCapsules exhibited high cellular uptake efficiency and cytotoxicity for both HeLa and MCF-7 cancer cells. Therefore, this work may provide a promising strategy to design and develop various stimuli-responsive drug nanocapsules for the treatment of cancer or other diseases.

Amphiphilic Oxo-Bridged Ruthenium "Green Dimer" for Water Oxidation.

SummaryIn 1982, an oxo-bridged dinuclear ruthenium(III) complex, known as “blue dimer,” was discovered to be active for water oxidation. In this work, a new amphiphilic ruthenium “green dimer” 2, obtained from an amphiphilic mononuclear Ru(bda) (N-OTEG) (L1) (1; N-OTEG = 4-(2-(2-(2-methoxyethoxy)ethoxy)ethoxy)-pyridine; L1 = vinylpyridine) is reported. An array of mechanistic studies identifies “green dimer” 2 as a mixed valence of RuII-O-RuIII oxo-bridged structure. Bearing the same bda2- and amphiphilic axial ligands, monomer 1 and green dimer 2 can be reversibly converted by ascorbic acid and oxygen, respectively, in aqueous solution. More importantly, the oxo-bridged “green dimer” 2 was found to take water nucleophilic attack for oxygen evolution, in contrast to monomer 1 via radical coupling pathway for O-O bond formation. This is the first report of an amphiphilic oxo-bridged catalyst, which possesses a new oxygen evolution pathway of Ru-bda catalysts.

Amphiphilic ligand modified gold nanocarriers to amplify lanthanide loading for ultrasensitive DELFIA detection of Cronobacter.

Conventional dissociation-enhanced lanthanide (Ln3+) fluoroimmunoassays (DELFIAs) using Ln3+ chelate-labeled antibodies as molecular probes exhibit limited sensitivity because of their relatively low Ln3+ labeling ratio per biomolecule. Herein, we applied gold nanoflowers (AuNFs) as amplified nanocarriers to increase the Ln3+ labeling ratio in a single molecular binding event for improving the sensitivity of traditional DELFIA. Two thiolated amphiphilic ligands (thiolated ethylenediaminetetraacetic acid (EDTA) and thiolated acylhydrazine-terminated ligands), consisting of a hydrophobic alkane chain, oligo(ethylene glycol) unit, and functional terminal of the EDTA or acylhydrazine group, were designed for the surface modification of AuNFs. The resultant ligand-coated AuNFs exhibited dual functions of Ln3+ chelation via the EDTA group and oriented attachment of antibodies via the acylhydrazine group. By utilizing 80 nm AuNFs as amplified carriers, we demonstrated that the maximum Eu3+ loading amount reached 1.07 × 104 Eu3+ ions per AuNF, which is approximately two to three orders of magnitude higher than that of traditional molecular probes, thereby amplifying the luminescence signal and enhancing the sensitivity of DELFIA. By combining a magnetic-mediated sandwich-type DELFIA method, the designed amplified AuNF nanoprobes achieved an ultrasensitive luminescence detection of Cronobacter muytjensii with a limit of detection (LOD) of 1.2 × 102 cfu mL-1 in a powdered infant formula. This LOD value was ca. 230-fold lower than that of the traditional colorimetric immunoassay. The designed signal amplification strategy using bifunctional ligand-modified AuNFs as enhanced Ln3+ nanocarriers provided a huge potential for building various ultrasensitive luminescence immunoassays for in vitro biodetection.

Binding Energetics of Charged Amphiphilic Ligands to Thermoresponsive Biodegradable Poly(methoxyethylaminophosphazene) Hydrogels.

Changes in the affinity of the swollen and collapsed forms of a thermoresponsive polymer gel for targeted ligands can be directly estimated using a thermodynamic approach based on high-sensitivity differential scanning calorimetry (HS-DSC). For macromolecular ligands (proteins) bound to the gel, this method provides information on changes in their conformational stability, which is of crucial importance for the biological or pharmaceutical activity of the protein. We used HS-DSC for the study of interactions of two widely administrated drugs-gemfibrozil and ibuprofen-and two globular proteins-α-lactalbumin and BSA-with hydrogels of the cross-linked poly(methoxyethylaminophosphazene). The gel collapse resulted in a substantial increase in the gel affinity for the drugs. We obtained quantitative estimations of the affinity of the collapsed gels depending on the gel structure, pH, concentration of NaCl, and phosphate buffer (an inductor of the thermoresponsivity). The gels retained a high affinity for the drugs in the near-physiological conditions (ionic composition and pH). The binding curves of globular proteins to the gels in the swollen and collapsed states were obtained. The different proteins demonstrated the preferential binding to the swollen or collapsed state of the gels, presumably depending on the protein surface hydrophobicity. The proteins bound to the gel subchains retain their native tertiary structure and, therefore, maintain their functionality when immobilized in the polyphosphazene hydrogels.

Mannose-Coated Fluorescent Lipid Microparticles for Specific Cellular Targeting and Internalization via Glycoreceptor-Induced Phagocytosis.

In this work, we report on the development of mannose-coated fluorescent lipid microparticles to study the role of C-type lectin membrane receptors in phagocytosis. The micrometric droplets of soybean oil-in-water emulsion were functionalized with a tailor-made fluorescent mannolipid. The amphiphilic ligand was built from a mannose unit, a lipid C11 spacer, and a naphthalimide fluorophore. The functionalization of the droplets was monitored by fluorescence microscopy as well as their interaction with concanavalin A, which was used as a model lectin in vitro. The use of a monovalent ligand on the surface of emulsion droplets yielded particles with an affinity approximately 40 times higher than that of free mannose. In cellulo, the coated droplets were shown to be specifically internalized by macrophages in a receptor-dependent phagocytic pathway. The naked droplets, on the other hand, displayed very little internalization because of their low immunogenicity. This work thus brings evidence that C-type lectin membrane receptors may act as phagocytic receptors. The functionalization of the droplets with the tailored amphiphilic fluorescent ligand also provides insights into the development of organic fluorescent particles that may prove useful for developing targeted imaging and delivery tools.

Salen-Based Amphiphiles: Directing Self-Assembly in Water by Metal Complexation.

Tuning morphologies of self‐assembled structures in water is a major challenge. Herein we present a salen‐based amphiphile which, using complexation with distinct transition metal ions, allows to control effectively the self‐assembly morphology in water, as observed by Cryo‐TEM and confirmed by DLS measurements. Applying this strategy with various metal ions gives a broad spectrum of self‐assembled structures starting from the same amphiphilic ligand (from cubic structures to vesicles and micelles). Thermogravimetric analysis and electric conductivity measurements reveal a key role for water coordination apparently being responsible for the distinct assembly behavior.

Copper(II) complexes with spherical morphology generated in one step by amphiphilic ligands: in situ view of the self-assembling, characterization, catalytic activity

Cyclotri- and tetrasiloxanes having a methyl group and a carboxylic acid coupled through thioether bridge at each silicon atom were used to coordinate copper(II). The amphiphilic character conferred by the co-existence of the two moieties with opposite behaviour on the silicon atom gives the molecule the ability to form aggregates in solution. When copper salt is added, the metal is quickly coordinated by carboxyl groups within these aggregates, as in situ taken microscopy images and video reveal, forming blue spheres. This morphology was confirmed by scanning and transmission electron microscopy, while the coordinating structures and their compositions were estimated by IR spectroscopy and UV–Vis diffuse reflectance spectroscopy, wide angle X-ray diffraction and energy-dispersive X-ray analysis. The wetting tests and moisture sorption analysis indicate hydrophobic materials, while thermal analysis shows a thermal stability of at least up to 180 °C. The compounds catalyze the decomposition of H2O2 in alkaline medium, the values found for the rate constant being between 0.8 and 3.8 × 10−3s-1.

Design of Small Nanoparticles Decorated with Amphiphilic Ligands: Self-Preservation Effect and Translocation into a Plasma Membrane.

Design of nanoparticles (NPs) for biomedical applications requires a thorough understanding of cascades of nano-bio interactions at different interfaces. Here, we take into account the cascading effect of NP functionalization on interactions with target cell membranes by determining coatings of biomolecules in biological media. Cell culture experiments show that NPs with more hydrophobic surfaces are heavily ingested by cells in both the A549 and HEK293 cell lines. However, before reaching the target cell, both the identity and amount of recruited biomolecules can be influenced by the pristine NPs' hydrophobicity. Dissipative particle dynamics (DPD) simulations show that hydrophobic NPs acquire coatings of more biomolecules, which may conceal the properties of the as-engineered NPs and impact the targeting specificity. Based on these results, we propose an amphiphilic ligand coating on NPs. DPD simulations reveal the design principle, following which the amphiphilic ligands first curl in solvent to reduce the surface hydrophobicity, thus suppressing the assemblage of biomolecules. Upon attaching to the membrane, the curled ligands extend and rearrange to gain contacts with lipid tails, thus dragging NPs into the membrane for translocation. Three NP-membrane interaction states are identified that are found to depend on the NP size and membrane surface tension. These results can provide useful guidelines to fabricate ligand-coated NPs for practical use in targeted drug delivery, and motivate further studies of nano-bio-interactions with more consideration of cascading effects.

Amphiphilic ligands for Cu-catalyzed aerobic oxidation to synthesize 9-fluorenones in water

A series of amphiphilic PEG-functionalized nitrogen ligands were developed for the highly efficient copper-catalyzed aerobic oxidation of 9-fluorenes, with molecular oxygen as the sole oxidant in neat water. A broad range of functional groups are well tolerated and thus offer the opportunity for further functionalization.

Mixed Fluorinated/Hydrogenated Self-Assembled Monolayer-Protected Gold Nanoparticles: In Silico and In Vitro Behavior.

Gold nanoparticles (AuNPs) covered with mixtures of immiscible ligands present potentially anisotropic surfaces that can modulate their interactions at complex nano-bio interfaces. Mixed, self-assembled, monolayer (SAM)-protected AuNPs, prepared with incompatible hydrocarbon and fluorocarbon amphiphilic ligands, are used here to probe the molecular basis of surface phase separation and disclose the role of fluorinated ligands on the interaction with lipid model membranes and cells, by integrating in silico and experimental approaches. These results indicate that the presence of fluorinated amphiphilic ligands enhances the membrane binding ability and cellular uptake of gold nanoparticles with respect to those coated only with hydrogenated amphiphilic ligands. For mixed monolayers, computational results suggest that ligand phase separation occurs on the gold surface, and the resulting anisotropy affects the number of contacts and adhesion energies with a membrane bilayer. This reflects in a diverse membrane interaction for NPs with different surface morphologies, as determined by surface plasmon resonance, as well as differential effects on cells, as observed by flow cytometry and confocal microscopy. Overall, limited changes in monolayer features can significantly affect NP surface interfacial properties, which, in turn, affect the interaction of SAM-AuNPs with cellular membranes and subsequent effects on cells.

Confined Complexation Reaction of Metal Ions with a Lipophilic Surfactant at the Water/Air Interface: A New Understanding Based on Surface Experiments and Molecular Dynamics Simulations.

Understanding the fundamentals of confined chemical reaction was an important subject in various heterogeneous physicochemical processes. Here, we investigated the orientation behavior of an amphiphilic ligand, the tri- n-octylphosphine oxide (TOPO), in a compressed monolayer at the air/water interface and its impact on the complexation reactivity of TOPO molecules with chromate ions at the interface. The analysis of sum frequency generation and polarization modulation infrared reflection absorption spectroscopy experiments combined with surface pressure measurements reveals a significant dependence of the adsorption rate and saturated concentration of chromate ions on the orientation of TOPO molecules during the increase of the surface pressure. In parallel, the analysis of molecular dynamics simulations indicates that the interaction energy between TOPO molecules and chromate ions is strongly sensitive to the orientation of TOPO molecules confined at the water/air interface. The present work provides a novel insight into the unique chemical reactivity of molecules in a confined microenvironment, and it provides a basis for further progresses in improving chemical reactivity and selectivity of molecules in a confined environment by regulating confinement of molecules.

Bionanomaterials for the Delivery of Cancer Immunotherapy.

Prof. Bourquin and her group focus on novel bioinspired strategies for the targeting of the immune system to treat cancer. The group investigates how nanoparticles of different types can be used to mimic bacteria or viruses in order to trigger immunity in cancer patients. The nanoparticles are first screened for potential toxicity or functional effects on immune cells. They are then loaded with immune-modulating drugs and selected for their capacity to trigger immune responses. Finally, their potential to block tumor growth is examined. This article describes how bioengineered particles made from spider silk can serve as vaccine, how gold nanoparticles coated with an amphiphilic ligand shell can transport highly effective immunomodulatory molecules to the tumor-draining lymph nodes, and how to screen particle interactions with immune cells in a standardized manner.