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.

Femtosecond Laser-Controlled Tip-to-Tip Assembly and Welding of Gold Nanorods.

Directed assembly of gold nanorods through the use of dithiolated molecular linkers is one of the most efficient methodologies for the morphologically controlled tip-to-tip assembly of this type of anisotropic nanocrystals. However, in a direct analogy to molecular polymerization synthesis, this process is characterized by difficulties in chain-growth control over nanoparticle oligomers. In particular, it is nearly impossible to favor the formation of one type of oligomer, making the methodology hard to use for actual applications in nanoplasmonics. We propose here a light-controlled synthetic procedure that allows obtaining selected plasmonic oligomers in high yield and with reaction times in the scale of minutes by irradiation with low fluence near-infrared (NIR) femtosecond laser pulses. Selective inhibition of the formation of gold nanorod n-mers (trimers) with a longitudinal localized surface plasmon in resonance with a 800 nm Ti:sapphire laser, allowed efficient trapping of the (n - 1)-mers (dimers) by hot spot mediated photothermal decomposition of the interparticle molecular linkers. Laser irradiation at higher energies produced near-field enhancement at the interparticle gaps, which is large enough to melt gold nanorod tips, offering a new pathway toward tip-to-tip welding of gold nanorod oligomers with a plasmonic response at the NIR. Thorough optical and electron microscopy characterization indicates that plasmonic oligomers can be selectively trapped and welded, which has been analyzed in terms of a model that predicts with reasonable accuracy the relative concentrations of the main plasmonic species.

Nucleation of Amyloid Oligomers by RepA-WH1-Prionoid-Functionalized Gold Nanorods.

Understanding protein amyloidogenesis is an important topic in protein science, fueled by the role of amyloid aggregates, especially oligomers, in the etiology of a number of devastating human degenerative diseases. However, the mechanisms that determine the formation of amyloid oligomers remain elusive due to the high complexity of the amyloidogenesis process. For instance, gold nanoparticles promote or inhibit amyloid fibrillation. We have functionalized gold nanorods with a metal-chelating group to selectively immobilize soluble RepA-WH1, a model synthetic bacterial prionoid, using a hexa-histidine tag (H6). H6-RepA-WH1 undergoes stable amyloid oligomerization in the presence of catalytic concentrations of anisotropic nanoparticles. Then, in a physically separated event, such oligomers promote the growth of amyloid fibers of untagged RepA-WH1. SERS spectral changes of H6-RepA-WH1 on spherical citrate-AuNP substrates provide evidence for structural modifications in the protein, which are compatible with a gradual increase in ß-sheet structure, as expected in amyloid oligomerization.

Using inclusion complexes with cyclodextrins to explore the aggregation behavior of a ruthenium metallosurfactant.

The aggregation behavior of a chiral metallosurfactant, bis(2,2'-bipyridine)(4,4'-ditridecyl-2,2'-bipyridine)ruthenium(II) dichloride (Ru2(4)C13), synthesized as a racemic mixture was characterized by small-angle neutron scattering, light scattering, NMR, and electronic spectroscopies. The analysis of the SANS data indicates that micelles are prolate ellipsoids over the range of concentrations studied, with a relatively low aggregation number, and the micellization takes place gradually with increasing concentration. The presence of cyclodextrins (ß-CD and γ-CD) induces the breakup of the micelles and helps to establish that micellization occurs at a very slow exchange rate compared to the NMR time scale. The open structure of this metallosurfactant enables the formation of very stable complexes of 3:1 stoichiometry, in which one CD threads one of the hydrocarbon tails and two CDs the other, in close contact with the polar head. The complex formed with ß-CD, more stable than the one formed with the wider γ-CD, is capable of resolving the Δ and Λ enantiomers at high CD/surfactant molar ratios. The chiral recognition is possible due to the very specific interactions taking place when the ß-CD covers-via its secondary rim-part of the diimine moiety connected to the hydrophobic tails. A SANS model comprising a binary mixture of hard spheres (complex + micelles) was successfully used to study quantitatively the effect of the CDs on the aggregation of the surfactant.

σ-Hole···π and lone pair···π interactions in benzylic halides.

Intermolecular and intramolecular halogen···π interactions in benzylic halides (Ph-CR2-X; X = F, Cl, Br and I) derived from 7-phenylnorbornane were investigated. The imposed geometry of the 7-arylnorbornane moiety prevents the participation of intramolecular attractive interactions between the σ-hole region of the halogen atom and the π electrons of the aromatic ring. Crystallographic data show intermolecular halogen bonds in iodide 1 and bromide 2 in the solid state. On the other hand, both UV-Vis and D-NMR data suggest the occurrence of intramolecular interactions between the halogen atoms and the phenyl rings in these compounds in solution. To provide more insight into the nature of the observed stabilizing interactions, density functional calculations were also carried out. These computations confirm the presence of genuine lone pairπ intramolecular interactions which strongly affect the stability and the electronic structure of these species.

Polyrotaxane-mediated self-assembly of gold nanospheres into fully reversible supercrystals.

The use of a thiol-functionalized nonionic surfactant to stabilize spherical gold nanoparticles in water induces the spontaneous formation of polyrotaxanes at the nanoparticle surface in the presence of the macrocycle α-cyclodextrin. Whereas using an excess of surfactant an amorphous gold nanocomposite is obtained, under controlled drying conditions the self-assembly between the surface supramolecules provides large and homogenous supercrystals with hexagonal close packing of nanoparticles. Once formed, the self-assembled supercrystals can be fully redispersed in water. The reversibility of the crystallization process may offer an excellent reusable material to prepare gold nanoparticle inks and optical sensors with the potential to be recovered after use.

The impact of dihydrogen phosphate anions on the excited-state proton transfer of harmane. Effect of ß-cyclodextrin on these photoreactions.

Photoinduced proton transfer reactions of harmane (1-methyl-9H-pyrido[3,4-b]indole) (HAR) in the presence of a proton donor/acceptor such as dihydrogen phosphate anions in aqueous solution have been studied by stationary and time-resolved fluorescence spectroscopy. The presence of high amounts of dihydrogen phosphate ions modifies the acid/base properties of this alkaloid. Thus, by keeping the pH constant at pH 8.8 and by increasing the amount of NaH(2)PO(4) in the solution, it is possible to reproduce the same spectral profiles as those obtained in high alkaline solutions (pH >12) in the absence of NaH(2)PO(4). Under these conditions, a new fluorescence profile appears at around 520 nm. This result could be related to the results of a recent investigation which suggests that a high intake of phosphates may promote skin tumorigenesis. The presence of ß-cyclodextrin (ß-CD) avoids the proton transfer reactions in this alkaloid by means the formation of an inclusion complex between ß-CD and HAR. The formation of this complex originates a remarkable enhancement of the emission intensity from the neutral form in contrast to the cationic and zwitterionic forms. A new lifetime was obtained at 360 nm (2.5 ns), which was associated with the emission of this inclusion complex. At this wavelength, the fluorescence intensity decay of HAR can be described by a linear combination of two exponentials. From the ratio between the pre-exponential factors, we have obtained a value of K = 501 M for the equilibrium of formation of this complex.

On the connection between the complexation and aggregation thermodynamics of oxyethylene nonionic surfactants.

Density and sound velocity data for aqueous solutions containing nonionic surfactants of the homologue series of polyoxyethylene(n) nonyl phenyl ethers (NPEn, n = 5 and 40) were analyzed in the absence and presence of beta-cyclodextrin (beta-CD) at 298 K. Thus, the critical micelle concentration of the surfactants and their apparent and partial molar volumes and compressibilities were measured. From a pseudophase separation model, the partial molar volumes and compressibilities of both pure surfactants in the micelle state and those of NPE40 in the monomer phase have been determined directly. For the ternary systems, increases of the molar volumes and compressibilities of NPE5 and NPE40 at infinite dilution and shifts of the cmc were observed compared to the binary systems. Luminescent measurements of the complexation process between NPE40 and beta-CD showed 1:1 + 1:2 (NPEn/2 beta-CD) stoichiometries for the complexes, with thermodynamic equilibrium constants that were in good agreement with previous results for NPE5 in the presence of beta-CD. This resemblance allowed us to use these results to indirectly determine the molar partial properties of NPE5 in the monomer state and understand the changes in the thermodynamic properties of NPE5 due to aggregation. From the aggregation and complexation data, a folding of the surfactants at the monomer state, in which the hydrophobic moieties of NPEn are surrounded by the EO chain, has been found. The oxyethylene group contributions at the monomer and micelle state of the NPEn homologue series have been estimated. The values of the transfer thermodynamic properties of both surfactants and beta-CD at infinite dilution conditions have been discussed in terms of a new extended model, in which the balance between the released water from the cavities of two beta-CDs and the different hydrophobic moieties of the surfactant that enter the macrocycle was considered.

Complexation and chiral drug recognition of an amphiphilic phenothiazine derivative with beta-cyclodextrin.

Promethazine hydrochloride (PTZ) is an amphiphilic drug derived from the phenothiazine structure that possesses a charged aliphatic chain with a chiral carbon. In the presence of beta-cyclodextrin (beta-CD), this drug undergoes significant changes of its photophysical properties in aqueous solution. Fluorescence spectroscopy measurements show the formation of a 1:1 stoichiometry complex with quantum yield lower than that of the pure PTZ, and two fluorescence lifetimes, which can be assigned to the free and complexed forms of the drug. In addition, (1)H NMR spectra, and 2D rotating-frame Overhauser enhancement spectroscopy (ROESY) were used to characterize the drug and the complex, and to determine the effects of the complexation on the aggregation. For the drug binary system, a noncooperative association process is observed, and in the presence of macrocycle, the chemical shifts reveal a chiral resolution of the drug enantiomers, with different stability constants of the complexes. beta-CD modifies the aggregation of PTZ in an extension that confirms the formation of a 1:1 complex. ROE enhancements and molecular modeling strategies show the most likely structure of the complex in solution, in which one of the phenyl rings is buried into the CD cavity, with a slight inclusion of the aliphatic part.

Supramolecular Control over the Interparticle Distance in Gold Nanoparticle Arrays by Cyclodextrin Polyrotaxanes.

Amphiphilic nonionic ligands, synthesized with a fixed hydrophobic moiety formed by a thiolated alkyl chain and an aromatic ring, and with a hydrophilic tail composed of a variable number of oxyethylene units, were used to functionalize spherical gold nanoparticles (AuNPs) in water. Steady-state and time-resolved fluorescence measurements of the AuNPs in the presence of α-cyclodextrin (α-CD) revealed the formation of supramolecular complexes between the ligand and macrocycle at the surface of the nanocrystals. The addition of α-CD induced the formation of inclusion complexes with a high apparent binding constant that decreased with the increasing oxyethylene chain length. The formation of polyrotaxanes at the surface of AuNPs, in which many α-CDs are trapped as hosts on the long and linear ligands, was demonstrated by the formation of large and homogeneous arrays of self-assembled AuNPs with hexagonal close packing, where the interparticle distance increased with the length of the oxyethylene chain. The estimated number of α-CDs per polyrotaxane suggests a high rigidization of the ligand upon complexation, allowing for nearly perfect control of the interparticle distance in the arrays. This degree of supramolecular control was extended to arrays formed by AuNPs stabilized with polyethylene glycol and even to binary arrays. Electromagnetic simulations showed that the enhancement and distribution of the electric field can be finely controlled in these plasmonic arrays.

Study of the interaction between a nonyl phenyl ether and beta-cyclodextrin: declouding nonionic surfactant solutions by complexation.

Absorption and fluorescence measurements for aqueous solutions at 298 K containing pentaoxyethylene nonyl phenyl ether (NPE5), in the absence and presence of beta-cyclodextrin (beta-CD), were analyzed to determine the effect of the complexation on the aggregation of the surfactant. For the binary system, the appearance of a new emission band and the presence of an isoemissive point in the emission spectra at the time and frequency domains indicate the formation of an excimer within the micellar core. The addition of beta-CD induces the formation of an inclusion complex strong enough to break the aggregates and avoid the excimer formation. For the ternary system, the increase in fluorescence has been used to assess the binding constants of 1:1 + 2:1 stoichiometries. Static light scattering, 1H NMR diffusion-ordered spectroscopy (DOSY), and two-dimensional rotating-frame Overhauser enhancement spectroscopy (ROESY) experiments were used to characterize the cloud point of NPE5 at 298 K, and to ascertain the effects of complexation on the clouding process. In the presence of beta-CD, the analysis of the 1H NMR spectra and the self-diffusion coefficients reveal the existence of interactions between the beta-CD and the aggregates that increase the cloud-point concentration more than expected. Under conditions of excess of beta-CD, ROE enhancements point to a complex of dominant 2:1 stoichiometry (beta-CD:NPE5) in which the hydrophobic moiety of the surfactant threads two beta-CDs.

Femtosecond laser reshaping yields gold nanorods with ultranarrow surface plasmon resonances.

The irradiation of gold nanorod colloids with a femtosecond laser can be tuned to induce controlled nanorod reshaping, yielding colloids with exceptionally narrow localized surface plasmon resonance bands. The process relies on a regime characterized by a gentle multishot reduction of the aspect ratio, whereas the rod shape and volume are barely affected. Successful reshaping can only occur within a narrow window of the heat dissipation rate: Low cooling rates lead to drastic morphological changes, and fast cooling has nearly no effect. Hence, a delicate balance must be achieved between irradiation fluence and surface density of the surfactant on the nanorods. This perfection process is appealing because it provides a simple, fast, reproducible, and scalable route toward gold nanorods with an optical response of exceptional quality, near the theoretical limit.

Inclusion complexes between beta-cyclodextrin and a Gemini surfactant in aqueous solution: an NMR study.

(1)H NMR spectra, diffusion-ordered NMR (DOSY), and 2D rotating-frame Overhauser enhancement spectroscopy (ROESY) experiments for aqueous solutions at 298 K containing the gemini surfactant, bis (dodecyl dimethylammonium)diethyl ether dibromide (12-EO(1)-12), in the absence and presence of beta-cyclodextrin (beta-CD) were used to characterize the surfactant and to determine the effects of the complexation in the micellization. For the binary system, the critical micelle concentration (cmc), the aggregation number, the stepwise micellization constant, and the size of the monomer have been obtained by studying the dependence of the chemical shifts and the self-diffusion coefficients with the concentration of surfactant. For the ternary system, the analysis of the (1)H NMR spectra and the self-diffusion coefficients reveal the formation of complexes of 1:1 and 2:1 stoichiometry (beta-CD:gemini), with a calculated stability constant for the second binding step higher than that of the first. The values of the hydrodynamic radii of the complexes were obtained from the calculated diffusion coefficients. The presence of beta-CD modifies the cmc in an extension that indicates mainly the formation of a 2:1 complex. The analysis of the chemical shifts of the surfactant indicates the nonparticipation of the complexes into the micelles. ROE enhancements depend substantially on the amount of the macrocycle added and therefore on the stoichiometry; at low concentrations of beta-CD, one of the hydrocarbon chains binds favorably with the cavity whereas the other interacts with the outer face. By contrast, at higher concentrations of beta-CD, the two hydrocarbon tails are included in two different macrocycles.

Intracellular pH-Induced Tip-to-Tip Assembly of Gold Nanorods for Enhanced Plasmonic Photothermal Therapy.

The search for efficient plasmonic photothermal therapies using nonharmful pulse laser irradiation at the near-infrared (NIR) is fundamental for biomedical cancer research. Therefore, the development of novel assembled plasmonic gold nanostructures with the aim of reducing the applied laser power density to a minimum through hot-spot-mediated cell photothermolysis is an ongoing challenge. We demonstrate that gold nanorods (Au NRs) functionalized at their tips with a pH-sensitive ligand assemble into oligomers within cell lysosomes through hydrogen-bonding attractive interactions. The unique intracellular features of the plasmonic oligomers allow us to significantly reduce the femtosecond laser power density and Au NR dose while still achieving excellent cell killing rates. The formation of gold tip-to-tip oligomers with longitudinal localized surface plasmon resonance bands at the NIR, obtained from low-aspect-ratio Au NRs close in resonance with 800 nm Ti:sapphire 90 fs laser pulses, was found to be the key parameter for realizing the enhanced plasmonic photothermal therapy.

Cooperative Self-Assembly Transfer from Hierarchical Supramolecular Polymers to Gold Nanoparticles.

The transfer of information encoded by molecular subcomponents is a key phenomenon that regulates the biological inheritance in living organisms, yet there is a lack of understanding of related transfer mechanisms at the supramolecular level in artificial multicomponent systems. Our contribution to tackle this challenge has focused on the design of a thiolated π-conjugated linking unit, whose hierarchical, cooperative self-assembly in nonpolar media can be efficiently transferred from the molecular to the nanoscopic level, thereby enabling the reversible self-assembly of gold nanoparticle (AuNP) clusters. The transfer of supramolecular information by the linking π-system can only take place when a specific cooperative nucleation-elongation mechanism is operative, whereas low-ordered noncooperative assemblies formed below a critical concentration do not suffice to extend the order to the AuNP level. To the best of our knowledge, our approach has allowed for the first time a deep analysis of the hierarchy levels and thermodynamics involved in the self-assembly of AuNPs.

Enhancement of the chemiluminescence of two isoluminol derivatives by nanoencapsulation with natural cyclodextrins.

The chemiluminescence (CL) yield of two isoluminol derivatives, N-(4-aminobutyl)-N-ethylisoluminol (ABEI) and N-(6-aminohexyl)-N-ethylisoluminol (AHEI), is remarkably increased in the presence of natural cyclodextrins (CDs). The most notable effect is produced by the addition of gamma-CD that produces enhancements up to 15-fold in the light emission of both compounds. Although proton nuclear magnetic resonance ((1)H NMR) measurements prove the encapsulation of these luminescent reagents in the CDs, with more stable associations by decreasing the width of the CD cavity, the improvement in the light emission of ABEI and AHEI is mainly due to the topology of the complexes. Evaluation of the rotating frame Overhauser effect spectroscopy (ROESY) spectra cross-peaks combined with semirigid-docking simulations has been used to gather information about the spatial conformation of the guest molecules into the CDs. These calculations have shown that a deeper inclusion in the CD cavity of the heterocyclic moiety of the luminescent molecules is directly related with a higher enhancement in the CL. The augment of the CL by natural CDs is of interest for increasing the detection limit in biochemical assays or liquid chromatography, for example, in which the CL of these compounds serves to quantify other molecular species that may take part, direct or indirectly, in the luminescent reaction.

Natural cyclodextrins as efficient boosters of the chemiluminescence of luminol and isoluminol: exploration of potential applications.

The chemiluminescent oxidation of luminol (LUM) and isoluminol (ISOL) is notably enhanced, both in intensity and duration, in the presence of natural cyclodextrins (alpha-, beta-, gamma-CD). The experiments have considered some of the most widespread applications of these compounds: the determination of metal cations and the revealing of bloodstains by oxidation with hydrogen peroxide in alkaline solution in the presence of Co(II), Fe(III), human hemoglobin, and blood, in order to explore potential applications. The largest enhancement in the emitted intensity occurs for the reaction of LUM with Co(II) in the presence of beta-CD. The use of the more soluble gamma-CD permits to expand the range of concentration and obtain more intense emission, although soluble derivatives of the beta-CD (methyl, hydroxypropyl-beta-CD, and a soluble cross-linked epichlorhydrin polymer) do not improve the chemiluminescence (CL) yield. In the case of hemoglobin and diluted human blood, the CDs aid in producing more light but only at high concentration of CDs, with a more lasting luminescence, up to three times longer. The changes in CL when glucose is used instead, much lower than with any of the CDs, imply that the cyclic structure of these oligosaccharides plays a key factor in the boosting of the emission. The results are explained in terms of the binding between the luminescent intermediate of the reaction, 3-aminophthalate (3-AP) and the CD, rather than to the luminescent reactant itself. The association constants obtained by steady-state fluorescence by assuming 1:1 stoichiometries reveal that the most stable association occurs between beta-CD and the intermediate, in accordance with the trend in the chemiluminescence. The topology of the complex deduced via ROESY experiments confirms a shallow inclusion of the double-charged intermediate by the primary rim of the CD, which accounts for the low stability of the complexes.

Solid crystal network of self-assembled cyclodextrin and nonionic surfactant pseudorotaxanes.

The title system allows the straightforward formation of three-dimensional crystals of self-assembled pseudorotaxanes formed by the nonionic surfactant Igepal CO-520 and beta-cyclodextrin (beta-CD) in aqueous solution. The work involves a combination of X-ray powder diffraction, high resolution electron transmission microscopy, and (13)C CP/MAS NMR studies of the solid crystal, supported by single crystal structural analysis. The results indicate a lamellar self-assembly of pseudorotaxanes with preferential orientation and disorder in the structure. For the single crystal, the unit cell was found to be triclinic (P1) and contains a beta-CD dimer. The surfactant molecules are located in the channel formed by these dimers along the c axis of the crystal network. The individual pseudorotaxane structure is formed by a dimer of beta-CDs threaded by the oxyethylene hydrophilic segment of Igepal CO-520, and a beta-CD dimer that binds the hydrophobic region of the surfactant. Thus, as in a CD polyrotaxane structure, this system results in an ordered self-assembly of pseudorotaxanes through the formation of a network of hydrogen bonds between head-to-head beta-CD dimers. Moreover, the analysis of the (1)H NMR spectra in solutions of pseudorotaxanes formed by beta-CD and Igepals with different lengths of the hydrophilic tails indicates equal stoichiometry patterns of both oxyethyelene and hydrophobic regions for the different supramolecules. Whereas the common hydrophobic moiety threads two macrocycles, the ratio between complexed oxyehtlyene segments and beta-CD is 2.5 for the hydrophilic tails. All these results show that nonionic surfactants can be used as alternative and effective linear threads to polymers and copolymers in the synthesis of supramolecular polyrotaxane solid crystals with CDs.