Supramolecular Large Nanosheets Assembled at Air/Water Interfaces and in Solution from Amphiphilic Heptagon-Containing Nanographenes.

We report the synthesis of a new set of amphiphilic saddle-shaped heptagon-containing polycyclic aromatic hydrocarbons (PAHs) functionalized with tetraethylene glycol chains and their self-assembly into large two-dimensional (2D) polymers. An in-depth analysis of the self-assembly mechanism at the air/water interface has been carried out, and the proposed arrangement models are in good agreement with the molecular dynamics simulations. Quite remarkably, the number and disposition of the tetraethylene glycol chains significantly influence the disposition of the PAHs at the interface and conditionate their packing under pressure. For the three compounds studied, we observed three different behaviors in which the aromatic core is parallel, perpendicular, and tilted with respect to the water surface. We also show that these curved PAHs are able to self-assemble in solution into remarkably large sheets of up to 150 µm2. These results show the relationship, within a family of curved nanographenes, between the monomer configuration and their self-assembly capacity in air/water interfaces and organic-water mixtures.

Amphiphilic polymers for aggregation-induced emission at air/liquid interfaces.

Polymersomes and related self-assembled nanostructures displaying Aggregation-Induced Emission (AIE) are highly relevant for plenty of applications in imaging, biology and functional devices. Experimentally simple, scalable and universal strategies for on-demand self-assembly of polymers rendering well-defined nanostructures are highly desirable. A purposefully designed combination of amphiphilic block copolymers including tunable lengths of hydrophilic polyethylene glycol (PEGm) and hydrophobic AIE polymer poly(tetraphenylethylene-trimethylenecarbonate) (P(TPE-TMC)n) has been studied at the air/liquid interface. The unique 2D assembly properties have been analyzed by thermodynamic measurements, UV-vis reflection spectroscopy and photoluminescence in combination with molecular dynamics simulations. The (PEG)m-b-P(TPE-TMC)n monolayers formed tunable 2D nanostructures self-assembled on demand by adjusting the available surface area. Tuning of the PEG length allows to modification of the area per polymer molecule at the air/liquid interface. Molecular detail on the arrangement of the polymer molecules and relevant molecular interactions has been convincingly described. AIE fluorescence at the air/liquid interface has been successfully achieved by the (PEG)m-b-P(TPE-TMC)n nanostructures. An experimentally simple 2D to 3D transition allowed to obtain 3D polymersomes in solution. This work suggests that engineered amphiphilic polymers for AIE may be suitable for selective 2D and 3D self-assembly for imaging and technological applications.

Optimization of Amino Acid Sequence of Fmoc-Dipeptides for Interaction with Lipid Membranes.

Fmoc-dipeptides appear as highly relevant building blocks in smart hydrogels and nanovehicles for biological applications. The interactions of the Fmoc-dipeptides with the cell membrane determine the efficiency of the nanomaterials based on the Fmoc-dipeptides' internalization of nanovehicles for drug delivery. Here, we aim to understand the interplay of the interactions between the Fmoc-dipeptides and a phospholipid surface as a function of the amino acid sequence. The DMPA (1,2-dimyristoyl- sn-glycero-3-phosphate) phospholipid in Langmuir monolayers was used as a model cell surface. A set of seven derivatives of Fmoc-dipeptides with a broad range of hydrophobicity were included. Mixed monolayers composed of DMPA/Fmoc-dipeptides in an equimolar ratio were built and characterized in situ at the air/water interface. Surface pressure-molecular area isotherms (π- A), Brewster angle microscopy (BAM), and UV-vis reflection spectroscopy (Δ R) were combined to provide a holistic picture of the interactions of the Fmoc-dipeptide with the phospholipid molecules. An increase in the hydrophobicity led to enhanced interaction of the Fmoc-dipeptide and DMPA molecules. The compression of the mixed monolayer could displace a significant fraction of the Fmoc-dipeptide from the monolayer. High hydrophobicity promoted self-assembly of the Fmoc-dipeptides over interaction with the phospholipid surface. The interplay of these two phenomena was analyzed as a function of the amino acid sequence of the Fmoc-dipeptides. The toxicity effect of Fmoc-FF could be observed and detailed at the molecular level. This study suggests that the adjustment of the hydrophobicity of the Fmoc-dipeptides within a defined range might optimize their efficiency for interaction with the lipid membranes. A semiquantitative guide for the chemical design of Fmoc-dipeptides for biological applications is proposed herein.

Mimicking the bioelectrocatalytic function of recombinant CotA laccase through electrostatically self-assembled bioconjugates.

Unprecedented 3D nanobiosystems composed of recombinant CotA laccases and citrate-stabilised gold nanoparticles have been successfully achieved by an electrostatic self-assembly strategy. The bioelectrochemical reduction of O2 driven by CotA laccase at the spore coat was mimicked. Consequently key insights into its bioelectrocatalytic function were unravelled.

Subtle chemical modification for enrichment of Fmoc-amino acid at a phospholipid interface.

Amino acids including the Fmoc group (9-fluorenylmethyloxycarbonyl) are bioinspired molecules that display intriguing features in self-assembly and biological applications. The influence of a delicate chemical modification between Fmoc-F and Fmoc-Y on the interaction with a phospholipid surface was analyzed. Langmuir monolayers of the 1,2-dimyristoyl-sn-glycero-3-phosphate (DMPA) phospholipid were used to mimic the eukaryotic cell membrane. In situ Brewster angle microscopy and UV-vis reflection spectroscopy provided insights on the effect of the Fmoc-amino acid derivatives on the DMPA phospholipid. The formation of H-bonds between the Fmoc-Y and the DMPA molecules was assessed, demonstrating the crucial role of the hydroxyl group of Fmoc-Y in enhancing the interaction with biosurfaces.

Fluorinated CdSe/ZnS quantum dots: Interactions with cell membrane.

Fluorescent inorganic quantum dots are highly promising for biomedical applications as sensing and imaging agents. However, the low internalization of the quantum dots, as well as for most of the nanoparticles, by living cells is a critical issue which should be solved for success in translational research. In order to increase the internalization rate of inorganic CdSe/ZnS quantum dots, they were functionalized with a fluorinated organic ligand. The fluorinated quantum dots displayed an enhanced surface activity, leading to a significant cell uptake as demonstrated by in vitro experiments with HeLa cells. We combined the experimental and computational results of Langmuir monolayers of the DPPC phospholipid as a model cell membrane with in vitro experiments for analyzing the mechanism of internalization of the fluorinated CdSe/ZnS quantum dots. Surface pressure-molecular area isotherms suggested that the physical state of the DPPC molecules was greatly affected by the quantum dots. UV-vis reflection spectroscopy and Brewster Angle Microscopy as in situ experimental techniques further confirmed the significant surface concentration of quantum dots. The disruption of the ordering of the DPPC molecules was assessed. Computer simulations offered detailed insights in the interaction between the quantum dots and the phospholipid, pointing to a significant modification of the physical state of the hydrophobic region of the phospholipid molecules. This phenomenon appeared as the most relevant step in the internalization mechanism of the fluorinated quantum dots by cells. Thus, this work sheds light on the role of fluorine on the surface of inorganic nanoparticles for enhancing their cellular uptake.

Surface-Active Fluorinated Quantum Dots for Enhanced Cellular Uptake.

Fluorescent nanoparticles, such as quantum dots, hold great potential for biomedical applications, mainly sensing and bioimaging. However, the inefficient cell uptake of some nanoparticles hampers their application in clinical practice. Here, the effect of the modification of the quantum dot surface with fluorinated ligands to increase their surface activity and, thus, enhance their cellular uptake was explored.

Unravelling the 2D self-assembly of Fmoc-dipeptides at fluid interfaces.

Dipeptides self-assemble into supramolecular structures showing plenty of applications in the nanotechnology and biomedical fields. A set of Fmoc-dipeptides with different aminoacid sequences has been synthesized and their self-assembly at fluid interfaces has been assessed. The relevant molecular parameters for achieving an efficient 2D self-assembly process have been established. The self-assembled nanostructures of Fmoc-dipeptides displayed significant chirality and retained the chemical functionality of the aminoacids. The impact of the sequence on the final supramolecular structure has been evaluated in detail using in situ characterization techniques at air/water interfaces. This study provides a general route for the 2D self-assembly of Fmoc-dipeptides.

Organization and structure of mixed Langmuir films composed of polydiacetylene and hemicyanine.

Mixed Langmuir monolayers of 10,12-Pentacosadiynoic acid (DA) monomer and an amphiphilic Hemicyanine dye derivative have been formed at the air/water interface. Two derivatives of docosylpyridinium have been used, with either one included in the monolayer in 1:1molar ratio. The DA monomers within the mixed monolayers have been polymerized in situ at the air/water interface. The crystalline structure of the monolayer and the kinetics of polymerization have been probed by grazing incidence X-ray diffraction (GIXD). The polymerization of DA proceeds with no phase segregation, exclusively leading to the red polydiacetylene form. The kinetics of polymerization at the air/water interface has been monitored in situ by GIXD. The experimental results have been combined with Molecular Mechanics computer simulations, revealing that DA molecules are sequentially arranged with molecules of Hemicyanine dye in alternating rows. The hydrophobic chains of the dye molecules act as spacers between the DA monomers. Surprisingly, such molecular arrangement does not hinder the in situ photopolymerization of DA. The mechanism of polymerization of DA within the mixed Langmuir monolayers has been convincingly described in molecular detail. This approach for interfacial polymerization of DA holds great potential for optically active devices and nanostructures comprising self-assembled thin films based in polydiacetylene.

Tailoring a compact and stable Langmuir bi-dimensional PbX-based layered perovskite film at the air-water interface and on solid support.

The present work studies the stability of Langmuir organic-inorganic superlattice materials thin films consisting of layered perovskite-based films with controlled 2D framework as well as to design experimental conditions for increasing the efficiency of the organic-inorganic perovskite motif by mechanical stimulus. Therefore, a whole covering of the air/water interface by a compact and stable lead-based layered perovskite structure is pursued. A 2D layered perovskite-type hybrid structure of the form [(CH3(CH2)19NH3)2(PbX4)], X=Cl, and Br, in which, two-dimensional sheets stabilized by a inner bilayer of organic monoammonium cation matrix, is mechanically tailored by successive compression-expansion cycles. The formation of 2D molecular patterns has been characterized by ΔR, BAM, XRD and XPS.

Mechanosensitive Gold Colloidal Membranes Mediated by Supramolecular Interfacial Self-Assembly.

The ability to respond toward mechanical stimuli is a fundamental property of biological organisms at both the macroscopic and cellular levels, yet it has been considerably less observed in artificial supramolecular and colloidal homologues. An archetypal example in this regard is cellular mechanosensation, a process by which mechanical forces applied on the cell membrane are converted into biochemical or electrical signals through nanometer-scale changes in molecular conformations. In this article, we report an artificial gold nanoparticle (Au NP)-discrete π-conjugated molecule hybrid system that mimics the mechanical behavior of biological membranes and is able to self-assemble into colloidal gold nanoclusters or membranes in a controlled and reversible fashion by changing the concentration or the mechanical force (pressure) applied. This has been achieved by rational design of a small π-conjugated thiolated molecule that controls, to a great extent, the hierarchy levels involved in Au NP clustering by enabling reversible, cooperative non-covalent (π-π, solvophobic, and hydrogen bonding) interactions. In addition, the Au NP membranes have the ability to entrap and release aromatic guest molecules reversibly (Kb = 5.0 × 105 M-1) for several cycles when subjected to compression-expansion experiments, in close analogy to the behavior of cellular mechanosensitive channels. Not only does our hybrid system represent the first example of a reversible colloidal membrane, but it also can be controlled by a dynamic mechanical stimulus using a new supramolecular surface-pressure-controlled strategy. This approach holds great potential for the development of multiple colloidal assemblies within different research fields.

Octadecyl-viologen Photooxidation in Surface Films: Macroscopic Contraction of Langmuir Monolayer by UV Irradiation.

The effects of UV radiation on a viologen derivative, octadecylviologen (OV), in Langmuir monolayers at the air-aqueous solution interface and in Langmuir-Blodgett (LB) films have been investigated. Langmuir monolayers suffer a sharp contraction after UV irradiation, clearly visible by the drop in surface pressure or the loss of surface area observed in the surface pressure-area isotherms. The UV-vis reflection measurements reveal a deep change in the OV monolayer caused by a photochemical reaction, which suggests the pyridones formation as photoreaction products. LB films (Z type), before and after being irradiated with UV light, have been studied by using UV-vis absorption and infrared and X-ray photoelectron spectroscopy. The results confirm that after the photodegradation of the viologen films, the presence of oxygen results in the appearance of pyridones as reaction products. This article demonstrates that, in the absence of catalysts, the photooxidation of viologen surface films occurs only under a particular molecular organization imposed by the air-water interface.

UV-Vis Reflection-Absorption Spectroscopy at air-liquid interfaces.

UV-Visible Reflection-Absorption Spectroscopy (UVRAS) technique is reviewed with a general perspective on fundamental and applications. UVRAS is formally identical to IR Reflection-Absorption Spectroscopy (IRRAS), and therefore, the methodology developed for this IR technique can be applied in the UV-visible region. UVRAS can be applied to air-solid, air-liquid or liquid-liquid interfaces. This review focuses on the use of UVRAS for studying Langmuir monolayers. We introduce the theoretical framework for a successful understanding of the UVRAS data, and we illustrate the usage of this data treatment to a previous study from our group comprising an amphiphilic porphyrin. For ultrathin films with a thickness of few nm, UVRAS produces positive or negative bands when p-polarized radiation is used, depending on the incidence angle and the orientation of dipole absorption. UVRAS technique provides highly valuable information on tilt of chromophores at the air-liquid interface, and moreover allows the determination of optical parameters. We propose UVRAS as a powerful technique to investigate the in situ optical properties of Langmuir monolayers.

Direct observation by using Brewster angle microscopy of the diacetylene polimerization in mixed Langmuir film.

Mixed Langmuir monolayers of 10,12-Pentacosadiynoic acid (DA) and amphiphilic hemicyanine (HSP) have been fabricated at the air-water interface. The mixed monolayer has been proved to be completely homogeneous. The DA molecules are arranged in a single monolayer within the mixed Langmuir monolayer, as opposed to the typical trilayer architecture for the pure DA film. Brewster angle microscopy has been used to reveal the mesoscopic structure of the mixed Langmuir monolayer. Flower shape domains with internal anisotropy due the ordered alignment of hemicyanine groups have been observed. Given the absorption features of the hemicyanine groups at the wavelength used in the BAM experiments, the enhancement of reflection provoked by the absorption process leads to the observed anisotropy. The ordering of such groups is promoted by their strong self-aggregation tendency. Under UV irradiation at the air-water interface, polydiacetylene (PDA) has been fabricated. In spite a significant increase in the domains reflectivity has been observed owing to the modification in the mentioned enhanced reflection, the texture of the domains remains equal. The PDA polymer chain therefore grows in the same direction in which the HSP molecules are aligned. This study is expected to enrich the understanding and design of fabrication of PDA at interfaces.

Diacetylene mixed Langmuir monolayers for interfacial polymerization.

Polydiacetylene (PDA) and its derivatives are promising materials for applications in a vast number of fields, from organic electronics to biosensing. PDA is obtained through polymerization of diacetylene (DA) monomers, typically using UV irradiation. DA polymerization is a 1-4 addition reaction with both initiation and growth steps with topochemical control, leading to the "blue" polymer form as primary reaction product in bulk and at interfaces. Herein, the diacetylene monomer 10,12-pentacosadiynoic acid (DA) and the amphiphilic cationic N,N'-dioctadecylthiapentacarbocyanine (OTCC) have been used to build a mixed Langmuir monolayer. The presence of OTCC imposes a monolayer supramolecular structure instead of the typical trilayer of pure DA. Surface pressure, Brewster angle microscopy, and UV-vis reflection spectroscopy measurements, as well as computer simulations, have been used to assess in detail the supramolecular structure of the DA:OTCC Langmuir monolayer. Our experimental results indicate that the DA and OTCC molecules are sequentially arranged, with the two OTCC alkyl chains acting as spacing diacetylene units. Despite this configuration is expected to prevent photopolymerization of DA, the polymerization takes place without phase segregation, thus exclusively leading to the red polydiacetylene form. We propose a simple model for the initial formation of the "blue" or "red" PDA forms as a function of the relative orientation of the DA units. The structural insights and the proposed model concerning the supramolecular structure of the "blue" and "red" forms of the PDA are aimed at the understanding of the relation between the molecular and macroscopical features of PDAs.

UV-Vis reflection spectroscopy under variable angle incidence at the air-liquid interface.

The UV-Vis reflection spectroscopy (UV-Vis-RS) in situ at the air-liquid interface provides information about tilt and aggregation of chromophores in Langmuir monolayers. This information is particularly important given in most cases the chromophore is located at the polar region of the Langmuir monolayer. This region of the Langmuir monolayers has been hardly accessible by other experimental techniques. In spite of its enormous potential, the application of UV-Vis-RS has been limited mainly to reflection measurements under light normal incidence or at lower incidence angles than the Brewster angle. Remarkably, this technique is quite sensitive to the tilt of the chromophores at values of incidence angles close to or larger than the Brewster angle. Therefore, a novel method to obtain the order parameter of the chromophores at the air-liquid interface by using s- and p-polarized radiation at different incidence angles is proposed. This method allowed for the first time the experimental observation of the two components with different polarization properties of a single UV-Vis band at the air-liquid interface. The method of UV-Vis spectroscopy under variable angle incidence is presented as a new tool for obtaining rich detailed information on Langmuir monolayers.

From two-dimensional to three-dimensional at the air/water interface: the self-aggregation of the acridine dye in mixed monolayers.

The formation of well-defined supramolecular structures on the nanoscopic scale is a fundamental step in nanotechnology. The fine control of the layer-by-layer growth of the supramolecular assemblies at interfaces is most desirable. The collapse of a mixed monolayer composed of two surfactants in an equimolar ratio (the organic dye N-10-dodecyl acridine (DAO) and stearic acid (SA)) is analyzed herein. The collapse process of the DAO/SA mixed monolayer has been monitored using surface pressure-molecular area (π-A) and surface potential isotherms, UV-visible reflection spectroscopy, polarization-modulated infrared reflection-absorption spectroscopy (PM-IRRAS), Brewster angle microscopy (BAM), and synchrotron-based in situ X-ray reflectivity (XRR) measurements. The collapse of the DAO/SA mixed monolayer leads to an ordered trilayer. The growth of anisotropic 2D domains of micrometric size is observed during the formation of the trilayer, related to the ordering of the acridine polar headgroups. The trilayer is organized with the first and third monolayers displaying the polar headgroups pointing to the aqueous subphase, whereas the intermediate layer displays the polar headgroups pointing to the air. The trilayer is stabilized by the strong self-aggregation acridine dye group of the DAO molecule. The controlled transition from a monolayer to a trilayer described herein is proposed as a model for further interfacial supramolecular structures of tunable thickness comprising organic dyes.

Molecular interaction of Rifabutin on model lung surfactant monolayers.

Tuberculosis is one of the most relevant problems for global health care. The design of new drugs against tuberculosis is aimed at maximizing impact against the disease, as well as minimizing the toxicological effect on the lung surfactant. In this work, the antituberculosis drug Rifabutin is studied in combination with phospholipid Langmuir monolayers as models of the lung surfactant monolayer. The zwitterionic 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC) and the anionic 1,2-dipalmitoyl-sn-glycero-3-phospho-(1'-rac-glycerol) (DPPG) were used as model phospholipids. A combination of in situ experimental techniques of Brewster angle microscopy, polarization-modulated infrared reflection-absorption spectroscopy, and UV-vis reflection spectroscopy with computer simulations has been used. The interactions between Rifabutin and the DPPC and DPPG Langmuir monolayers were described as the formation of an inclusion complex. The phospholipid-Rifabutin inclusion complex prevents the penetration of the Rifabutin into the alkyl chain region of the phospholipids, leading to a disruption of the monolayer structure and a possible toxicological effect.

Revisiting the Brewster Angle Microscopy: the relevance of the polar headgroup.

The Brewster Angle Microscopy (BAM) is a powerful microscopy technique allowing the in situ visualization of the morphology of Langmuir monolayers at the air/water interface. The use of the BAM for attaining structural insights in the molecular arrangement of the Langmuir monolayers is widespread. In this review, we examine the reflection of a Langmuir monolayer under a rather different perspective than classical: the influence of the polar headgroup of the amphiphiles in the BAM images is taken into account. The relevance of the polar headgroup as the main cause of the BAM features has been the focus of a reduced number of BAM studies. An emerging experimental and theoretical framework from recent bibliography is discussed. Different theoretical scenarios are considered, concerning the size and absorption of radiation of the polar headgroup. Two qualitative examples showing physical phenomena regarding the reflectivity changes in a BAM experiments are discussed. The anisotropy in the BAM images as inner textures is of special interest. Quantitative structural information of the molecular arrangement of the monolayer is obtained by simulating the textures of the domains observed. The quantitative assessment of the detailed molecular arrangement of the polar headgroup by BAM is highly valuable, as this information can hardly be obtained from other experimental techniques. The procedure for extracting quantitative structural data from the experimental BAM pictures is revised in detail from the recent bibliography for further application of this model to different Langmuir monolayers.

Chiral textures inside 2D achiral domains.

Chiral interfaces are of capital importance for biorecognition processes and nanotechnology. In this work, a mixed Langmuir monolayer was built using a surface-active dye and a phospholipid. The monolayer displayed optical activity. The driving force for the formation of the supramolecular chirality is the self-assembly of the polar headgroups of the dye. The existence of supramolecular chirality inside nonchirally-shaped domains is shown.