Search

In the present manuscript, we describe how we successfully used ligand-based virtual screening (LBVS) to identify two small-molecule, drug-like hit classes with excellent ADMET profiles against the difficult to address microbial enzyme 1-deoxy-D-xylulose-5-phosphate synthase (DXPS). In the fight against antimicrobial resistance (AMR) it has become increasingly important to address novel targets such as DXPS, the first enzyme of the 2C-methyl-D-erythritol-4-phosphate (MEP) pathway, which affords the universal isoprenoid precursors. This pathway is absent in humans but essential for pathogens such as Mycobacterium tuberculosis, making it a rich source of drug targets for the development of novel anti-infectives. Standard computer-aided drug-design tools, frequently applied in other areas of drug development, often fail for targets with large, hydrophilic binding sites such as DXPS. Therefore, we introduce the concept of pseudo-inhibitors, combining the benefits of pseudo-ligands (defining a pharmacophore) and pseudo-receptors (defining anchor points in the binding site), for providing the basis to perform a LBVS against M. tuberculosis DXPS. Starting from a diverse set of reference ligands showing weak inhibition of the orthologue from Deinococcus radiodurans DXPS, we identified three structurally unrelated classes with promising in vitro (against M. tuberculosis DXPS) and whole-cell activity including extensively drug-resistant strains of M. tuberculosis. The hits were validated to be specific inhibitors of DXPS and to have a unique mechanism of inhibition. Furthermore, two of the hits have a balanced profile in terms of metabolic and plasma stability and display a low frequency of resistance development, making them ideal starting points for hit-to-lead optimization of antibiotics with an unprecedented mode of action.

The recent success of mRNA vaccines using lipid-based vectors highlights the importance of strategies for nucleotide delivery under the pandemic situation. Although current mRNA delivery is focused on lipid-based vectors, still they need to be optimized for increasing stability, targeting, and efficiency, and for reducing toxicity. In this regard, other vector systems featuring smart strategies such as pH-responsive degradability and endosomal escape ability hold the potential to overcome the current limitations. Here, we report pH-responsive polymeric nanorods made of amino acid-derivatives connected by dynamic covalent bonds called proteoid-biodynamers, as mRNA vectors. They show excellent biocompatibility due to the biodegradation, and outstanding transfection. The biodynamers of Lys, His, and Arg or monomer mixtures thereof were shown to form nanocomplexes with mRNA. They outperformed conventional transfection agents three times regarding transfection efficacy in three human cell lines, with 82-98% transfection in living cells. Also, we confirmed that the biodynamers disrupted the endosomes up to 10-fold more in number than the conventional vectors. We discuss here their outstanding performance with a thorough analysis of their nanorod structure changes in endosomal microenvironments.

International audience; The detailed structure of active polymer gels built by integrating light-driven rotary molecular motors as reticulation units in polymer networks is discussed as a function of gel composition. Upon light-irradiation, the collective rotation of molecular motors is translated into the macroscopic contraction of the gels through polymer chains twisting. The major role of the characteristic ratio c/c* (c* being the overlap concentration of the polymer-motor conjugates before crosslinking) on the contraction efficiency is exploited. Combined small-angle neutron and X-ray scattering experiments reveal the importance of heterogeneities in the macroscopic contraction process: the mesh size of the network increases under irradiation in the whole range of c/c*, an increase that is maximal for c/c*=1; i.e. at higher contraction efficiency. Furthermore, the mesh size of the network reaches equilibrium within a short period of time, while the heterogeneiteis increase in size untill the end of the contraction process. Finally, the significant motorized twisting of polymer chains within the network allows to foresee the design of new storage energy systems.

Polymerization of carbazole dicarboxaldehydes and lysine derivatives by imine and acylhydrazone formation afforded peptide-derived molecular biodynamers. Characterization of their physicochemical properties revealed an interesting morphology change upon polymerization from monomers forming submicrometer spherical micelles to nanometer-sized rigid-rod-shaped polymeric particles. A combination of light-scattering methods, small-angle neutron scattering, and transmission electron microscopy enabled a detailed investigation of this morphological change. Moreover, we investigated by dynamic and static light scattering how the pH affects the fluorescence and size of the biodynamers. These morphological and pH-dependent changes are expected to open the door to a myriad of applications of molecular biodynamers.

Ammonium lithocholate nanotubes (NH4LC) have been prepared in alkaline ammonia solutions and exhibited remarkable monodisperse cross-sectional dimensions (external diameter = 52 nm) as shown by cryo-transmission electron microscopy measurements. A classical electroless metallic replication method was used with a single poly(ethylene-imine) PEI layer coating the negatively charged NH4LC nanotubes. Short copper rods (external diameter ∼ 80 nm) were observed by scanning electron microscopy that corresponded to the original organic templates. The results obtained in acidic conditions are analyzed in terms of the lifetime of the self-assembled structures and formation of bundles of tubes. Dynamic light scattering measurements and optical observations show that the system in the presence of controlled amounts of hydrochloric acid is stable enough to account for a metallic replication in acidic conditions. An average apparent diffusion coefficient of the organic NH4LC assemblies is extracted (D ∼ 9.8 × 105 nm2 s−1) in homogeneous suspensions where bundles have been dispersed by the acidic additions.

Mixing negatively charged polyelectrolyte (PEL) with positively charged gold nanoparticles (Au NPs) in aqueous solution results in electrostatics complexes of different shapes and compactness. Here, when complexing with a semirigid PEL hyaluronic acid (HA), we obtain crystals made of nanoparticles in a new region of the phase diagram, as evidenced by small-angle X-ray scattering (SAXS). The Au NPs were initially well dispersed in solution; their size distribution is well controlled but does not need to be extremely narrow. The bacterial hyaluronic acid, polydispersed, is commercially available. Such rather simple materials and mixing preparation produce a highly ordered crystalline phase of electrostatic complexes. The details of the interactions between spherical nanoparticles and linear polymer chains remain to be investigated. In practice, it opens a completely new and unexpected method of complexation. It has high potential, in particular because one can take advantage of the versatility of Au NPs associated with the specificity of biopolymers, varied due to natural biodiversity.

International audience; Dilute solutions of electronically active molecules capable of irradiation-driven supramolecular self-assembly are studied by dynamic light scattering. We detect unusual well-defined oscillations in the long time range of the homodyne intensity correlation function for all solutions that were irradiated with white light prior to the measurements. The oscillation effect is attributed to the local laser-induced heating of the samples due to strongly enhanced absorption manifested by the supramolecular filaments. It is found that the oscillation frequency depends on the irradiation time, solution concentration, and the incident laser power, but is independent of the scattering angle. These observations are explained with a semi-quantitative theory relating the oscillation effect to thermo-gravitational convection flows generated by laser beam. The results suggest that the presence of such homodyne oscillations could be a sensitive probe for aggregation in many complex systems.

A clickable fullerene hexa-adduct scaffold has been functionalized with twelve triarylamine subunits. The light-triggered self-assembly of this molecular unit leads to 3D honeycomb-like structures with inner pores of around 10 nm diameter. Multiple grafting of triarylamine subunits onto a hard-core C60 unit increases the dimensionality of the self-assembly process by reticulating the 1D nanowires typically obtained from the supramolecular polymerization of triarylamine monomers.

International audience; The implementation of molecular machines in polymer science is of high interest to transfer mechanical motions from nanoscale to macroscale in order to access new kinds of active devices and materials. Toward this objective, thermodynamic and topological aspects need to be explored for reaching efficient systems capable of producing a useful work. In this paper we describe the branched polymerization of pH-sensitive bistable [c2] daisy chain rotaxanes by using copper(I)-catalyzed Huisgen 1,3-dipolar cycloaddition (“click chemistry”). With this cross-linked topology, the corresponding materials in the form of chemical gels can be contracted and expanded over a large variation of volume (∼50%) by changing the protonation state of the system. HR-MAS 1H NMR and neutron scattering experiments reveal that this macroscopic response of the gels results from the synchronized actuation of the mechanical bonds at the molecular level.

The networking of individual artificial molecular motors into collective actuation systems is a promising approach for the design of active materials working out of thermodynamic equilibrium. Here, we report the first mechanical studies on active polymer gels built by integrating light-driven rotary molecular motors as reticulation units in polymer networks. We correlate the volume ratio before and after light irradiation with the change of the elastic modulus, and we reveal the universal maximum mechanical efficiency of such gels related to their critical overlap concentration before chemical reticulation. We also show the major importance of heterogeneities in the macroscopic contraction process and we confirm that these materials can increase their internal energy by the motorized winding of their polymer chains.

A range of doubly dynamic proteoid biodynamers based on the polycondensation of various categories of amino acid hydrazides with a dialdehyde have been generated through formation of two types of reversible C=N bonds (imine and acylhydrazone). Their structures and properties (rates of polymerization and dynamic character) have been characterized by NMR, small-angle neutron scattering, dynamic light scattering, and cryo-transmission-electron microscopy. Three types of structures (nanorods, globular nano-objects, oligomers) are obtained at different rates after polycondensation. Competitive polymerization shows that electrostatic effects markedly influence polymerizations when two oppositely charged monomers are used, and an exchange experiment demonstrates the preferential incorporation of a specific monomer in the biodynamer chain. Taken together, all our results show that the side chains of the amino acid hydrazides have a strong influence on the rates of polymerization, structures, and dynamic properties of the resulting biodynamers. The present study provides a basis for the rational design and synthesis of various types of well-ordered structures and adaptive materials, offering great potential for utilization in the field of biomaterials science.

An acid-base switchable [c2]daisy chain rotaxane terminated with two 2,6-diacetylamino pyridine units has been self-assembled with a bis(uracil) linker. The complementary hydrogen-bond recognition patterns, together with lateral van der Waals aggregations, result in the hierarchical formation of unidimensional supramolecular polymers associated in bundles of muscle-like fibers. Microscopic and scattering techniques reveal that the mesoscopic structure of these bundles depends on the extended or contracted states that the rotaxanes show within individual polymer chains. The observed local dynamics span over several length scales because of a combination of supramolecular and mechanical bonds. This work illustrates the possibility to modify the hierarchical mesoscopic structuring of large polymeric systems by the integrated actuation of individual molecular machines.

The condensation of aldehydes and amines in water to give amphiphilic imines can lead to a particular autocatalytic behavior known as autopoiesis, in which the closed micellar structure made by the amphiphile at the mesoscale can accelerate the condensation of its constituents. Herein, through a combination of analytical tools, including diffusion ordered spectroscopy (DOSY) as well as light, neutron, and X-ray scattering techniques, the thermodynamic and kinetic parameters were probed at both the level of dynamic covalent imine bond formation and the level of the resulting micellar self-assemblies. It was found that the autopoietic behavior was the result of a combination of several parameters, including solubilization of hydrophobic building blocks, template effect at the core-shell interface, and growth/division cycles of the micellar objects.

Dynamic proteoids are dynamic covalent analogues of proteins which are generated through the reversible polymerization of amino-acid- or peptide-derived monomers. The authors design and prepare a series of dynamic proteoids based on the reversible polycondensation of six types of dipeptide hydrazides bearing different categories of side chains. The polymerization and structures of biodynamers generated by 1 H-NMR spectroscopy, light scattering and cryo-transmission-electron microscopy are studied. This study shows that the presence of aromatic rings in the side chains plays the most essential role in determining the extent of the polymerization and organization into resultant nanostructures through π-π-stacking interactions, hydroxyl groups have a less favorable influence via hydrogen bonds, whereas a high density of positive charge blocks the generation of biodynamers due to electrostatic repulsions. These findings set the stage for the rational design and synthesis of dynamic proteoids as novel biofunctional materials.

Chemistry - a European journal 24(4), 798-802 (2018). doi:10.1002/chem.201705206, Published by Wiley-VCH, Weinheim

We study for the first time the structure of stable finite size clusters (i.e., colloidal molecules) obtained by self-assembly of cationic gold nanoparticles (i.e., atoms) mediated by a flexible polyanion. We reveal with nondenaturizing techniques a striking structural transition from 1D small chains of 12 gold nanoparticles (AuNPs) with a self-avoiding conformation to 3D fractal clusters of 130 AuNPs with short-range ordering around the charge inversion threshold. Interestingly, these well-defined structures are obtained by simple mixing in water without anisotropic functionalization or external forces. As a preliminary step, we introduce a new synthesis pathway leading to well-defined cationic AuNPs of controllable size that can be dispersed in H2O or D2O without aggregation and ligands' self-assemblies. On this occasion, we point for the first time that usual procedures do not enable to eliminate cationic ligands' self-assemblies that could play an undesired role in AuNPs' self-assembly through electrostatic interactions.

International audience; The implementation of artificial molecular machines in polymer science is an important objective that challenges chemists and physicists in order to access an entirely new class of smart materials. To design such systems, the amplification of a mechanical actuation from the nanoscale up to a macroscopic response in the bulk material is a central issue. In this article we show that bistable [c2]daisy chain rotaxanes (i.e. molecular muscles) can be linked into mainchain Upy-based supramolecular polymers. We then reveal by an in depth quantitative study that the pH actuation of the mechanically active rotaxane at the nanoscale influences the physical reticulation of the polymer chains by changing the supramolecular behavior of the Upy units. This nano-actuation within the local structure of the main chain polymer results in a mechanically controlled sol-gel transition at the macroscopic level.

International audience; In this article, the dynamic structure of complex supramolecular polymers composed of bistable [c2]daisy chain rotaxanes as molecular machines that are linked by ureidopyrimidinones (Upy) as recognition moieties was studied. pH actuation of the integrated mechanically active rotaxanes controls the contraction/extension of the polymer chains as well as their physical reticulation. Small-angle neutron and X-ray scattering were used to study in-depth the nanostructure of the contracted and extended polymer aggregates in toluene solution. The supramolecular polymers comprising contracted nanomachines were found to be equilibrium polymers with a mass that is concentration dependent in dilute and semidilute regimes. Surprisingly, the extended polymers form a gel network with a crystal-like internal structure that is independent of concentration and reminiscent of a pearl-necklace network.

Multiplication of functional units through self-assembly is a powerful way to new properties and functions. In particular, self-organization of components decorated with recognition groups leads to multivalent entities, amenable to strong and selective binding with multivalent targets, such as protein receptors. Here we describe an efficient, supramolecular, one-pot valency multiplication process proceeding through self-organization of monovalent components into well-defined, grid-shaped [2×2] tetranuclear complexes bearing eight sugar residues for multivalent interaction with the tetrameric lectin, concanavalin A (Con A). The grids are stable in water under physiological pH at a relatively high concentration, but dissociate readily at slightly more acidic pH or upon dilution below a certain threshold, in a type of on-off behavior. The carbohydrate-decorated grids interact strongly and selectively with Con A forming triply supramolecular bio-hybrid polymeric networks, which lead to a highly specific phase-separation and quasi-quantitative precipitation of Con A out of solution. Dramatic effects of valency number on agglutination properties were demonstrated by comparison of grids with divalent carbohydrates of covalent and non-covalent (L-shaped, mononuclear zinc complex) scaffolds. The results presented here provide prototypical illustration of the power of multivalency generation by self-assembly leading to defined arrays of functional groups and binding patterns.

Self-healing polymers are a class of functional polymers that, by the virtue of the presence of certain dynamic chemical linkages, may undergo self-repair at a mechanically cut surface. Herein we report the synthesis of a self-healing polymer giving access to double dynamicity within the polymer network by making use simultaneously of reversible covalent bonds and dynamic non-covalent hydrogen bonding interactions. These features are provided, respectively, by doubly dynamic cassettes comprising chemically reversible imine linkages and multiply hydrogen-bonded urea groups, connected by a siloxane-based backbone that imparts softness to the material. Such a system can be envisaged to give access to a broad spectrum of functional materials, which can be tuned by convenient modulation of the structural motifs of the polymer. © 2013 Society of Chemical Industry

Materials of supramolecular nature have attracted much attention owing to their interesting features, such as self-reparability and material robustness, that are imparted by noncovalent interactions to synthetic materials. Among the various structures and synthetic methodologies that may be considered for this purpose, the introduction of extensive arrays of multiple hydrogen bonds allows for the formation of supramolecular materials that may, in principle, present self-healing behavior. Hydrogen bonded networks implement dynamic noncovalent interactions. Suitable selection of structural units gives access to novel dynamic self-repairing materials by incrementing the number of hydrogen-bonding sites present within a molecular framework. Herein, we describe the formation of a tris-urea based motif giving access to six hydrogen-bonding sites, easily accessible through reaction of carbohydrazide with an isocyanate derivative. Extension towards the synthesis of multiply hydrogen-bonded supramolecular materials has been achieved by polycondensation of carbohydrazide with a bis-isocyanate component derived from poly-dimethylsiloxane chains. Such materials underwent self-repair at a mechanically cut surface. This approach gives access to a broad spectrum of materials of varying flexibility by appropriate selection of the bis-isocyanate component that forms the polymer backbone.

International audience; PACS 62.23.St Complex nanostructures, including patterned or assembled PACS 82.35.Rs Polyelectrolytes PACS 83.85.Hf X-ray and neutron scattering Abstract. Aggregation of nanoparticles of given size R induced by addition of a polymer strongly depends on its degree of rigidity. This is shown here on a large variety of silica nanoparticle self-assemblies obtained by electrostatic complexation with carefully selected oppositely charged bio-polyelectrolytes of different rigidity. The effective rigidity is quantified by the total persistence length L T representing the sum of the intrinsic (L p) and electrostatic (L e) polyelectrolyte persistence length, which depends on the screening, i.e., on ionic strength due to counterions and external salt concentrations. We experimentally show for the first time that the ratio L T /R is the main tuning parameter that controls the fractal dimension D f of the nanoparticles self-assemblies, which is determined using small-angle neutron scattering: (i) For L T /R1, L e is strongly increased due to the absence of salt and repulsions between nanoparticles cannot be compensated by the polyelectrolyte wrapping, which allow a spacing between nanoparticles and the formation of one dimensional pearl necklace complexes. (iv) Finally, electrostatic 2 screening, i.e. ionic strength, turned out to be a reliable way of controlling D f and the phase diagram behavior. It finely tunes the short-range interparticle potential, resulting in larger fractal dimensions at higher ionic strength.

The dependence between the size of gold nanoparticle (AuNP) and the citrate to gold molar ratio (X) is still a matter of debate 65years after the seminal work by Turkevich et al. for high X values. We assume that this dispersion of results is due to the variation of certain parameters that are often not mentioned in the protocols, and to the use of a single characterization technique (dynamic light scattering (DLS) or transmission electron microscopy (TEM)). To adress definitely the question of this dependence, we have synthesized AuNPs with very precise protocols ensuring that the only parameters to be modified are X and the sequence of reagent addition. We have then studied, for the first time, the dependence of the size with X quantitatively with a multimodal approach (UV-Visible spectroscopy, DLS and TEM) for 2 synthetic routes differing only by the sequence of reagent addition. We show unambiguously that AuNPs' size decay monotonically, with X whatever the order of reagent addition. It allows us to exclude the occurrence of a measurable discontinuity for a peculiar value of X that prompted some authors to postulate the existence of two different reaction pathways when the citrate to gold molar ratio is around this value. In contrast, our result is in line with one reaction pathway, likely a "seed-mediated" growth mechanism, which should leads to monotonic size decrease. Also, we note that our result agrees with the sole available theoretical prediction (Kumar et al., 2007) on the whole range of X. Despite this apparent agreement, we point some contradictions between recent experimental results and basal hypothesis of this model.

Polypeptide-type dynamic biopolymers (bio-dynamers) have been generated by polycondensation via acylhydrazone and imine formation of amino-acid-derived components that polymerize driven by self-organization. They have been characterized as globular particles, reminiscent of folded proteins, by cryo-TEM, LS, DOSY NMR, and SANS studies. The reversible polymers obtained show remarkably low dispersity and feature double covalent dynamics allowing for fine-tuning of both exchange and incorporation processes through pH control. In the course of build-up, they perform a selection of the most suitable building block, as indicated by the preferential incorporation of the more hydrophobic amino-acid component with increased rate and higher molecular weight of the polymer formed. The system described displays nucleation-elongation behavior driven by hydrophobic effects and represents a model for the operation of adaptation processes in the evolution of complex matter.

International audience; Supramolecular self-assembly is a multiple length-scale and time-dependent process involving many coexisting components. Such complexity requires suitable strategies to extract quantitative dynamical and structural information on all involved species. Here, we detail an original light scattering method to study the kinetics of tailored triarylamine molecules capable of self-assembling in supramolecular highly conductive nanowires upon light exposure. These micrometric assemblies cause the emergence of intermittences in the scattered intensity and the construction of a predominant slow mode in the correlation function making separation between small-and large-size species impossible using conventional treatments. Our strategy is based on the time monitoring of intermittences and allows us to determine the fraction of nanowires as well as those of small critical nuclei and triarylamine building blocks as a function of time and light exposure, in good agreement with recent theoretical predictions.

We have investigated the self-assembly in water of molecules having a single hydrophobic bis-urea domain linked to different hydrophilic functional side chains, i.e., bioactive peptidic residues and fluorescent cyanine dyes. By using a combination of spectroscopy, scattering, and microscopy techniques, we show that each one of these molecules can individually produce well-defined nanostructures such as twisted ribbons, two-dimensional plates, or branched fibers. Interestingly, when these monomers of different functionalities are mixed in an equimolar ratio, supramolecular copolymers are preferred to narcissistic segregation. Radiation scattering and imaging techniques demonstrate that one of the molecular units dictates the formation of a preferential nanostructure, and optical spectroscopies reveal the alternated nature of the copolymerization process. This work illustrates how social self-sorting in H-bond supramolecular polymers can give straightforward access to multifunctional supramolecular copolymers.

The structural and dynamic properties of low ionic strength micellar solutions of the cationic surfactant perfluorooctylbutane trimethylammonium bromide have been investigated by cryo-TEM, small-angle neutron scattering, small-angle X-ray scattering, T-jump and rheological experiments. The surfactant molecules self-assemble into narrow ribbons with average dimensions on the order of 4 nm x 3 nm, either under salt-free conditions or in the presence of up to 30 mM KBr or NaF. Cryo-TEM also reveals in the salt-free systems the presence of networks of multiconnected micelles. Rheological experiments showed that these surfactant systems exhibit a strong shear-thickening effect even in the presence of up to 30 mM KBr. The T-jump response of the micellar solutions was found to be multiexponential. This observation rules out the presence of only linear micelles with an exponential length distribution and suggests more complex topologies of the micellar aggregates. The relaxation time associated with the predominant process in the T-jump relaxation is strongly correlated to the critical shear rate beyond which shear thickening occurs, thus indicating that this critical shear rate is controlled by the micellar kinetics.

In this study, we have directly determined for the first time the structure and the chain conformation of hyaluronan, a model semirigid polyelectrolyte polysaccharide. At high ionic strength, detailed information on the chain flexibility has been obtained from combined light and small-angle neutron scattering experiments by applying different fitting methods based upon expressions for a single-chain scattering function of a wormlike chain without excluded volume. Particular attention has been given to the determination of the intrinsic persistence length, L0, and a value close to 90 A was found using the different fitting procedures. Without screening (i.e., at low ionic strength), the measured total persistence length appears increased by at least the amount predicted by Odijk for the electrostatic contribution, Le (∼κ-2, square of the Debye−Huckel screening length). This would mean this model was checked using classical polyelectrolytes. At high ionic strength the scattered intensity crosses over, with ...

Microtubule assembly from purified tubulin preparations involves both microtubule nucleation and elongation. Whereas elongation is well documented, microtubule nucleation remains poorly understood because of difficulties in isolating molecular intermediates between tubulin dimers and microtubules. Based on kinetic studies, we have previously proposed that the basic building blocks of microtubule nuclei are persistent tubulin oligomers, present at the onset of tubulin assembly. Here we have tested this model directly by isolating nucleation-competent cross-linked tubulin oligomers. We show that such oligomers are composed of 10-15 laterally associated tubulin dimers. In the presence of added free tubulin dimers, several oligomers combine to form microtubule nuclei competent for elongation. We provide evidence that these nuclei have heterogeneous structures, indicating unexpected flexibility in nucleation pathways. Our results suggest that microtubule nucleation in purified tubulin solution is mechanistically similar to that templated by gamma-tubulin ring complexes with the exception that in the absence of gamma-tubulin complexes the production of productive microtubule seeds from tubulin oligomers involves trial and error and a selection process.

Dynamic and static light scattering experiments were performed on 0.1 M NaCl aqueous solutions of semirigid hyaluronan and rigid xanthan in the dilute and semidilute regime. In the dilute regime, typical good solvent behavior is found, and the intrinsic persistence length of hyaluronan (≈100 A) and xanthan (≈1000 A) is determined. However, in the semidilute regime the time autocorrelation function of the scattered electric field is found to be bimodal for hyaluronan and xanthan solutions. The short time relaxation has a typical q-2 dependence and is attributed to the relaxation of concentration fluctuations characterized by a cooperative diffusion mechanism. The long time relaxation has a q-3 dependence, characteristic of intraparticle dynamics. This behavior is not consistent with predicted semidilute, good solvent system behavior but instead indicates the presence of associations or microgels. The corresponding slow relaxation times appear to be related to the macroscopic viscosity of the surrounding po...

The structural and dynamic properties of low ionic strength micellar solutions of the cationic surfactant perfluorooctylbutane trimethylammonium bromide have been investigated by means of dynamic and static light scattering and rheological experiments. In the range of concentration extending from the critical micelle concentration to about the overlap concentration, the surfactant self-assembles into micellar aggregates with sizes of the order of 100 nm. At higher concentrations, the system is characterized by a single correlation length consistent with the formation of a transient network of wormlike micelles. In the dilute regime, the solutions exhibit a very large shear thickening effect (up to 50) and a very slow recovery (hours) after a thermal or mechanical perturbation. The extent of consistency of the dynamical observations with the various possible structures inferred from the scattering data has been discussed. Some arguments are in favor of the presence of interlinked micellar rings in the quie...

By using a combination of experimental and theoretical tools, we elucidate unique physical characteristics of supramolecular triarylamine nanowires (STANWs), their packed structure, as well as the entire kinetics of the associated radical-controlled supramolecular polymerization process. AFM, small-angle X-ray scattering, and all-atomic computer modeling reveal the two-columnar "snowflake" internal structure of the fibers involving the π-stacking of triarylamines with alternating handedness. The polymerization process and the kinetics of triarylammonium radicals formation and decay are studied by UV-vis spectroscopy, nuclear magnetic resonance and electronic paramagnetic resonance. We fully describe these experimental data with theoretical models demonstrating that the supramolecular self-assembly starts by the production of radicals that are required for nucleation of double-columnar fibrils followed by their growth in double-strand filaments. We also elucidate nontrivial kinetics of this self-assembly process revealing sigmoid time dependency and complex self-replicating behavior. The hierarchical approach and other ideas proposed here provide a general tool to study kinetics in a large number of self-assembling fibrillar systems.

Dynamic covalent surfactants have been obtained by the reversible condensation of a hydrophobic aldehyde (ended by an ionic tip) with various neutral polyethylene glycol based hydrophilic amines. In water, the duality between the two hydrophilic domains (charged and neutral) leads to their segregation when the surfactants are self-assembled within micelles. Depending on the number of polyethylene glycol units, a core–shell inversion leading to a switching orientation of the ionic tips from the inside to the outside of the micelles has been demonstrated by a combination of scattering techniques. In competition experiments, when several amines of different pKas and hydrophilic polyethylene glycol chains are competing for the same aldehyde, it becomes possible to trigger this core–shell inversion by pH modulation and associated dynamic constitutional reorganization.

Dynamic and static light-scattering experiments were performed on aqueous solutions of the highly charged semiflexible polyelectrolyte chitosan in the dilute and the semidilute regime. In the dilute regime, typical good solvent behavior is found. However, in the overlapped regime the time autocorrelation function of the scattered electric field is found to be bimodal. The short time relaxation has a typical q2 dependence, characteristic of diffusion, and the long time relaxation an approximately q2 dependence, where q is the scattering wave vector. Static and dynamic light-scattering experiments were carried out to analyze the two modes. The fast mode is attributed to the relaxation of concentration fluctuations characterized by a cooperative diffusion mechanism of the polymer network meshes. The slow relaxation time appears to be related to the diffusion of polymer associations. The effect of the excess of salt concentration and polymer concentration was investigated.

The behavior of polymeric surfactant polyvinyl acetate (PVAC)-b-poly(1,1,2,2-tetrahydroperfluorooctyl acrylate) (PTAN) in supercritical carbon dioxide (CO2) was investigated using static and dynamic light scattering. We observed three regions on the phase diagram of the copolymer in supercritical CO2: (i) two-phase region at low CO2 density; (ii) solutions of spherical micelles at intermediate CO2 densities; (iii) solutions of unimers (individual copolymer chains) at high CO2 densities. The aggregation number (the number of copolymer chains in a micelle) decreases with an increasing density of supercritical CO2 in region (ii). An increase of the CO2 density corresponds to the improvement of solvent quality for both blocks of the copolymer (PVAC and PTAN). The hydrodynamic radius of micelles and unimers was measured using dynamic light scattering in regions (ii) and (iii), respectively. This light-scattering study is the first one reporting a solvent density-induced transition between spherical micelles a...

International audience; The electrostatic complexation between model negatively charged silica nanoparticles (NPs) with radius R~10 nm and chitosan, a natural polyelectrolyte bearing positive charges with a semi-rigid backbone of persistence length of Lp~9 nm, was studied by a combination of SANS, SAXS, light scattering, and cryo-TEM. In this system, corresponding to Lp/R~1, we observe the formation of (i) randomly branched complexes in the presence of an excess of chitosan chains and (ii) well-defined single-strand nanorods in 10 the presence of an excess of nanoparticles. We also observe no formation of nanorods for NPs with poly-L-lysine, a flexible polyelectrolyte, corresponding to Lp/R~0.1, suggesting a key role played by this ratio Lp/R. In the intermediate range of nanoparticles concentrations, we observe an associative phase separation (complex coacervation) leading to more compact complexes in both supernatant and coacervate phases. This method might open the door to a greater degree of control of nanoparticles self-15 assembly into larger nanostructures, through molecular structural parameters like Lp/R, combined with polyelectrolytes/nanoparticles ratio.

Double-dynamic polymers, incorporating both molecular and supramolecular dynamic features (“double dynamers”) have been generated, where these functions are present in a nonstoichiometric ratio in the main chain of the polymer. It has been achieved by (1) the formation of covalent oligo-dynamers in which the monomers are connected by reversible covalent interactions and (2) the association of these oligomers through supramolecular interactions (hydrogen bonding). This procedure leads to the formation of an entity that can be seen as a supramolecular polymer of molecular oligo-dynamers. It thus combines two types of dynamic processes that do not simply alternate in the polymeric chain but may be incorporated in various ratios. These non-alternating double dynamic polymers have been generated by sequential construction and the different steps have been characterized by NMR spectroscopy, mass spectrometry and light scattering.

Light scattering experiments were carried out on aqueous micellar solutions of cetylpyridinium chlorate (CPClO3) in the presence of sodium chlorate (NaClO3) as a function of surfactant concentration. The time autocorrelation function of the scattered field is found to be bimodal. The slow relaxation time, that is assumed to be the terminal time of the stress relaxation, is a decreasing function of the surfactant concentration. The behaviour of the plateau modulus obtained by combining measurements of the slow relaxation time and of the zero-shear viscosity suggests the presence of entanglements in these highly fluid micellar systems.

Pumping iron: Double-threaded rotaxanes can be linked to coordination units and polymerized in the presence of iron or zinc ions. pH modulation triggers cooperative contractions (or extensions) of the individual rotaxanes, thus resulting in an amplified motion of the muscle-like supramolecular chains with changes of their contour lengths of several micrometers (see picture).

Times Cited: 1; International audience; Interactions of plant tannins with polysaccharide hyaluronan are studied by means of light scattering and small-angle X-ray scattering (SAXS). In this paper, we show that (1) the tannin–polysaccharide complexes remain stable in colloidal suspension; (2) the masses and structures of colloidal tannin–polysaccharide objects depend on the tannin degree of polymerization; and (3) the densities of tannin–polysaccharide aggregates are about 7 times lower than the density of a single solvated polysaccharide molecule. Short tannins and polysaccharides are aggregated in loose oligomeric structures whose sizes are comparable to a single polysaccharide molecule. Tannins longer than 10 nm and polysaccharides are aggregated in larger microgel-like particles whose sizes exceed 200 nm.

International audience; In this paper we report the influence of biopolymer folding on nanoparticle spatial distribution in two typical bio-nanocomposite hydrogels. These systems consist of negatively charged nanosized fillers (polyoxotungstate clusters and silica particles, 2.2 nm and 23.0 nm in diameter, respectively) dispersed at low volume fractions in a positively charged gelatin hydrogel. The filler state of dispersion is investigated during triple helix folding by combining small-angle neutron scattering (SANS) and polarimetry experiments. Neutron contrast matching/polarimetry correlations indicate that the nanoparticle spatial distribution is clearly modified during triple helix folding for the two systems. In the first case, polyoxotungstate clusters are initially arranged in small finite size aggregates that grow with increasing triple helix rate: ΔRG ≈ +150% and ΔI(q → 0) ≈ +250% for Δ[helix] ≈ +40%. In the second case, silica particles initially form a connected network that undergoes a significant densification through gelatin conformational transition. In the two cases, the kinetics of triple helix folding is only slightly affected by the presence of the nanoparticles and their state of dispersion. In our experimental conditions, these two processes are almost thermo-reversible following triple helix unfolding.

International audience; We show by combining small-angle X-ray scattering (SAXS) and cryo-transmission electron microscopy (cryo-TEM) that anionic silica nanoparticles (SiNPs) assemble into well-defined 1D cluster when mixed with a dilute solution of semiflexible chitosan polycation. The nanorods are stable in excess of SiNPs and composed of 10 SiNPs well-ordered into straight single strands with length Lrod ≈ 184.0 nm and radius Rrod = 9.2 nm = RSiNPs. We point out that the ratio between the chitosan persistence length and the SiNP radius, which is here equal to 1, can be the determining condition to obtain such original objects.

International audience; We study by Small Angle Neutron Scattering (SANS) the structure of Hyaluronan -Lysozyme complexes. Hyaluronan (HA) is a polysaccharide of 9 nm intrinsic persistence length that bears one negative charge per disaccharide monomer (Mmol = 401.3 g/mol); two molecular weights, Mw = 6000 and 500 000 Da were used. The pH was adjusted at 4.7 and 7.4 so that lysozyme has a global charge of +10 and + 8 respectively. The lysozyme concentration was varied from 3 to 40 g/L, at constant HA concentration (10 g/L). At low protein concentration, samples are monophasic and SANS experiments reveal only fluctuations of concentration although, at high protein concentration, clusters are observed by SANS in the dense phase of the diphasic samples. In between, close to the onset of the phase separation, a distinct original scattering is observed. It is characteristic of a rod-like shape, which could characterize "single" complexes involving one or a few polymer chains. For the large molecular weight (500 000) the rodlike rigid domains extend to much larger length scale than the persistence length of the HA chain alone in solution and the range of the SANS investigation. They can be described as a necklace of proteins attached along a backbone of diameter one or a few HA chains. For the short chains (Mw ~ 6000), the rod length of the complexes is close to the chain contour length (~ 15 nm).

The structural variations of dynamic combinatorial mesophases are investigated in dilute aqueous solutions by a combination of small-angle-neutron, X-ray, and light scattering. The supramolecular structures are composed of self-assembled dynamic covalent hydrophobic and hydrophilic blocks (Dynablocks), linked together by reversible and pH-dependent imine bonds. When several Dynablocks compete from a set of constituents, it is possible to tune their molecular associations by pH modulation, which results in structuring variations of the supramolecular self-assemblies. We here demonstrate that even complex supramolecular mixtures of micellar and vesicular Dynablocks libraries can be quantitatively characterized by the complementarity of these three scattering techniques. It becomes thus envisageable for chemists to design very elaborated stimuli-responsive mesophases based on these objects which represent a new class of “smart” soft materials.

A set of carbazole- and benzene-derived di(aldehyde) and di(acylhydrazine) monomers containing hexaglyme groups to impart water solubility has been synthesized. Mixing a given di(aldehyde) and di(acylhydrazine) pair in acidic aqueous solution causes polymerization through reversible acylhydrazone condensation. The structures of the resultant amphiphilic polyacylhydrazones have been studied using 1H NMR spectroscopy, matrix-assisted laser desorption ionization mass spectrometry, small-angle neutron scattering, transmission electron microscopy, size exclusion chromatography/multi-angle laser light scattering (SEC-MALLS) and UV-visible and fluorescence spectrophotometries. All the available data support the existence of structurally related rod-like nanostructures of variable lengths and constant diameters of approximately 5 nm in all cases, which are interpreted as corresponding to individually folded polymer chains. On the basis of these studies, molecular models are proposed in which the hydrophobic, aromatic polymer backbones assume helical conformations allowing for hydrophobically driven π-stacking, while exposing the hydrophilic hexaglyme groups to the solvent. The molecular models are in agreement with the observed physical dimensions of the nanostructures, and are further supported by the observation of strong hypochromic effects on changing the solvent from dimethylformamide to water. Additionally, the reversible polymerization process is found to be cooperative. 1H NMR and SEC-MALLS studies reveal severe deviations from statistically predicted product distributions under imbalanced stoichiometry, which are characteristic of nucleation–elongation behaviour. Copyright © 2010 Society of Chemical Industry

International audience; Let there be more light: Triarylamine-based building blocks respond to visible-light exposure by the formation of cationic radicals that hierarchically self-assemble into molecular wires, which in turn combine within larger fibers (see picture). The stimuli-responsive supramolecular scaffold, which is created by charge transfer and reversibly broken up by heating, prevents the quenching of holes within the wires.

International audience; Dynamic glycopolymers have been generated by polycondensation through acylhydrazone formation between components bearing lateral bioactive oligosaccharide chains. They have been characterized as bottlebrush type by cryo-TEM and SANS studies. They present remarkable fluorescence properties whose emission wavelengths depend on the constitution of the polymer and are tunable by constitutional modification through exchange/incorporation of components, thus also demonstrating their dynamic character. Constitution-dependent binding of these glycodynamers to a lectin, peanut agglutinin, has been demonstrated.