Controlling Protein Assembly with Superchaotropic Nano-Ions.

In living systems, protein assemblies have essential functions, serving as structural supports, transport highways for molecular cargo, and containers of genetic material. The construction of protein assemblies, which involves control over space and time, remains a significant challenge in biotechnology. Here, we show that anionic boron clusters, 3,3'-commo-bis[closo-1,2-dicarba-3-cobaltadodecaborane] (COSAN-), and halogenated closo-dodecarboranes (B12X122-, X = Η, Cl or I), described as super-chaotropic nano-ions, induce the formation of 2D assemblies of model proteins, myoglobin, carbonic anhydrase, and trypsin inhibitor. We found that the nano-ion concentration reversibly controls the size of the protein assemblies. Furthermore, the secondary structures of the proteins are only slightly affected by assembly formation. For myoglobin, the formation of these assemblies even prevents temperature denaturation, highlighting a preservation effect of nano-ions. Our study reveals that inorganic boron-based nano-ions act as a reversible molecular glue for proteins, providing a potential starting point for the further development of controlled protein assemblies.

Toward Distinguishing between the Superchaotropic and Hydrophobic Characters of Nanometric-Sized Ions in Interaction with PEGylated Surfaces.

In this study, we explore the superchaotropic effect of various polyoxometalate or boron cluster nano-ions on hydrophilic neutral surfaces. Nano-ions, characterized by low charge densities, exhibit strong adsorption on non-ionic hydrophilic surfaces like PEGylated micelles. This adsorption phenomenon was attributed to the enthalpically favorable dehydration of nano-ions, the so-called superchaotropic effect. Here, we investigate the adsorption of three nano-ions, α-SiW12O404-, α-PW12O403-, and B12I122-, with decreasing charge density or increasing superchaotropicity (or hydrophobicity), on hydrophilic solid surfaces, PEGylated gold nanoparticles, and PEGylated gold-coated quartz crystal. Solid surfaces are devoid of hydrophobic regions, enabling the study of the subtle nuance between hydrophobic and superchaotropic effects. Unlike adsorption on PEGylated micelles, the adsorption constant decreases with a reduced charge density, aligning with the well-established principle that hydrophobic ions do not adsorb on hydrophilic surfaces. This research improves our understanding of the subtle difference between superchaotropic and hydrophobic effects in nano-ion adsorption phenomena.

Cooperative Self-Assembly Process Involving Giant Toroidal Polyoxometalate as a Membrane Building Block in Nanoscale Vesicles.

The self-assembly of organic amphiphilic species into various aggregates such as spherical or elongated micelles and cylinders up to the formation of lyotropic hexagonal or lamellar phases results from cooperative processes orchestrated by the hydrophobic effect, while those involving ionic inorganic polynuclear entities and nonionic organic components are still intriguing. Herein, we report on the supramolecular behavior of giant toroidal molybdenum blue-type polyoxometalate, namely, the {Mo154} species in the presence of n-octyl-ß-glucoside (C8G1), widely used as a surfactant in biochemistry. Structural investigations were carried out using a set of complementary multiscale methods including single-crystal X-ray diffraction analysis supported by molecular modeling, small-angle X-ray scattering and cryo-TEM observations. In addition, liquid NMR, viscosimetry, surface tension measurement, and isothermal titration calorimetry provided further information to decipher the complex aggregation pathway. Elucidation of the assembly process reveals a rich scenario where the presence of the large {Mo154} anion disrupts the self-assembly of the C8G1, well-known to produce micelles, and induces striking successive phase transitions from fluid-to-gel and from gel-to-fluid. Herein, intimate organic-inorganic primary interactions arising from the superchaotropic nature of the {Mo154} lead to versatile nanoscopic hybrid C8G1-{Mo154} aggregates including crystalline discrete assemblies, smectic lamellar liquid crystals, and large uni- or multilamellar vesicles where the large torus {Mo154} acts a trans-membrane component.

Switchable Redox and Thermo-Responsive Supramolecular Polymers Based on Cyclodextrin-Polyoxometalate Tandem.

Supramolecular polymers built from stimuli-responsive host-guest interactions represent an attractive way of tailoring smart materials. Herein, we exploit the chaotropic effect of polyoxometalates and related host-guest properties to design unconventional polymer systems with reversible redox and thermo-responsive sol-gel transition. These supramolecular networks result from the association of cyclodextrin-based oligomers and Keggin-type POMs acting as electro-active crosslinking agents. The structure and the dynamics of such self-assembly systems have been investigated using a multiscale approach involving MALDI-TOF, viscosity measurements, cyclic voltammetry, 1H-NMR (1D and DOSY), and Small-Angle X-ray Scattering. Our results reveal that the chaotropic effect corresponds to a powerful and efficient force that can be used to induce responsiveness in hybrid supramolecular oligomeric systems.

Foam Flotation of Clay Particles Using a Bifunctional Amine Surfactant.

Understanding clay flotation mechanisms has become a major concern because of the increasing level of environmental contamination of soil and ground water by heavy metals and radionuclides. Clays are often used as sorbents for extracting metals in indirect flotation processes but can function simultaneously as defoamers. However, how foam generation and stability depend on the molecular interactions between the clays and surfactant is still controversial. In the present study, an amine polyethoxylated surfactant was used as a bifunctional surfactant that collected clay particles and acted as a foaming agent in the flotation process. The pH conditions strongly affected the surfactant physicochemical properties, allowing the clay extraction efficiency to be tuned. The interfacial recovery factor of the clays almost reached 100% under acidic (pH < 6) and neutral (pH 6-10) conditions, whereas it was negative under alkaline conditions (pH > 10), contrary to expectations. To elucidate the mechanisms involved in the particle flotation process for each of the pH conditions, the bulk and foam phases were analyzed. The effects of electrostatic interactions between the solutes and multiscale structure on the clay extraction behavior were investigated by electrophoretic measurements, dynamic light scattering, small-angle neutron scattering, and image analysis. Based on these results, three flotation processes were found depending on pH range: surfactant foam fractionation at pH > 10; clay particle foam flotation at pH 6-10; and particle froth flotation at pH < 6.

When Ions Defy Electrostatics: The Case of Superchaotropic Nanoion Adsorption.

Nanometer-sized anions, like polyoxometalates and borate clusters, bind to nonionic hydrated matter driven by the chaotropic effect, which arises from the favorable dehydration of the ions. Herein, we evaluate the adsorption and activity coefficient of the superchaotropic Keggin polyoxometalate SiW12O404- (SiW) on nonionic surfactant (C8E4) micelles by modeling small-angle X-ray and neutron-scattering spectra. Neither hard sphere nor electrostatic repulsion models reproduce the experimental activity coefficient of adsorbed SiW ions on the micelles. However, the activity and binding of SiW on the micelles is well-described by a Langmuir adsorption isotherm. These results imply that adsorbed SiW ions are non-interacting and "create" around themselves adsorption sites on the micelle. The temperature dependence of the adsorption constant showed that the SiW adsorption is enthalpically driven and entropically unfavorable, in line with the typical chaotropic thermochemical signature. The adsorption enthalpy can be split into an electrostatic term and a water-recovery term to evaluate and qualitatively predict the superchaotropicity of a nanoion.

Repulsive, but sticky - Insights into the non-ionic foam stabilization mechanism by superchaotropic nano-ions.

HYPOTHESIS: The superchaotropic Keggin polyoxometalate α-SiW12O404- (SiW) was recently shown to stabilize non-ionic surfactant (C18:1E10) foams owing to electrostatic repulsion that arises from the adsorption of SiW-ions to the foam interfaces. The precise mechanism of foam stabilization by SiW however remained unsolved. EXPERIMENTS: Imaging and conductimetry were used on macroscopic foams to monitor the foam collapse under free drainage and small angle neutron scattering (SANS) at a given foam height allowed for the tracking of the evolution of film thickness under quasi-stationary conditions. Thin film pressure balance (TFPB) measurements enabled to quantify the resistance of single foam films to external pressure and to identify intra-film forces. FINDINGS: At low SiW/surfactant ratios, the adsorption of SiW induces electrostatic repulsion within foam films. Above a concentration threshold corresponding to an adsorption saturation, excess of SiW screens the electrostatic repulsion that leads to thinner foam films. Despite screened electrostatics, the foam and single foam films remain very stable caused by an additional steric stabilizing force consistent with the presence of trapped micelles inside the foam films that bridge between the interfaces. These trapped micelles can serve as a surfactant reservoir, which promotes self-healing of the interface leading to much more resilient foam films in comparison to bare surfactant foams/films.

Aqueous solubilization of hydrophobic compounds by inorganic nano-ions: An unconventional mechanism.

HYPOTHESIS: Solubilization of hydrophobic compounds in water is commonly performed by using organic solubilizers such as hydrotropes, surfactants, co-solvents, and macrocycles to form host-guest complexes. 3,3'-commo-bis[closo-1,2-dicarba-3-cobaltadodecaborane] derivatives (COSANs) are fully inorganic and non-amphiphilic ionic boron clusters with nanometric size (nano-ions) showing superchaotropic properties as they strongly bind to neutral organic molecules. Therefore, we expect COSANs to act as solubilizers of sparingly water-soluble molecules, but with a mechanism different from all other organic solubilizers known so far. EXPERIMENTS: The aqueous solubilization efficiency of COSANs towards butanol was evaluated by determining phase diagrams and comparing them to classical solubilizers. Nanostructuration of the mixture was studied using UV spectroscopy, small-angle X-ray, and neutron scattering with contrast variation. FINDINGS: COSANs act as efficient aqueous solubilizers of medium-chain alcohols (0.6 < log P < 1.5). Unlike surfactants, COSAN is an efficient solubilizer in its monomeric state, at concentrations well below its critical aggregation concentration. Solubilization by COSAN takes place with a bi-dimensional anisotropic growth of COSAN/butanol co-assemblies, whereas solubilization by surfactant occurs via an isotropic swelling of micelles. Appealingly, COSANs/2-butanol co-assemblies efficiently solubilize more hydrophobic compounds with log P values up to around 6, offering new opportunities in many applied fields.

Superchaotropic Nano-ion Binding as a Gelation Motif in Cellulose Ether Solutions.

Nanometer-sized anions (nano-ions) like polyoxometalates and boron clusters exhibit so-called superchaotropic behavior, which describes their strong binding to hydrated non-ionic matter in water. We show here that nano-ions, at millimolar concentrations, dramatically enhance the viscosity and induce gelation of aqueous solutions of non-ionic cellulose ethers (CEs), a class of widely utilized polymers known for their thickening and gel-forming ability. These phenomena arise from an interplay of attractive forces and repulsive electrostatic forces between CE-chains upon nano-ion binding. The attractive forces manifest themselves as aggregation of CE-chains into a physically crosslinked polymer network (gel). In turn, the electrostatic repulsions hamper the viscosity increase and gelation. Superchaotropic nano-ion binding emerges as a novel and general physical crosslinking motif for CE-solutions and exceeds by far the conventional thickening effects of classical salts and ionic surfactants.

Probing foams from the nanometer to the millimeter scale by coupling small-angle neutron scattering, imaging, and electrical conductivity measurements.

Liquid foams are multi-scale structures whose structural characterization requires the combination of very different techniques. This inherently complex task is made more difficult by the fact that foams are also intrinsically unstable systems and that their properties are highly dependent on the production protocol and sample container. To tackle these issues, a new device has been developed that enables the simultaneous time-resolved investigation of foams by small-angle neutron scattering (SANS), electrical conductivity, and bubbles imaging. This device allows the characterization of the foam and its aging from nanometer up to centimeter scale in a single experiment. A specific SANS model was developed to quantitatively adjust the scattering intensity from the dry foam. Structural features such as the liquid fraction, specific surface area of the Plateau borders and inter-bubble films, and thin film thickness were deduced from this analysis, and some of these values were compared with values extracted from the other applied techniques. This approach has been applied to a surfactant-stabilized liquid foam under free drainage and the underlying foam destabilization mechanisms were discussed with unprecedented detail. For example, the information extracted from the image analysis and SANS data allows for the first time to determine the disjoining pressure vs. thickness isotherm in a real, draining foam.

Superchaotropic nano-ions as foam stabilizers.

HYPOTHESIS: Weakly hydrated nanometric ions, called superchaotropes, were recently shown to adsorb strongly to non-ionic surfaces affecting drastically the surface's physical-chemical properties due to a charging effect. Superchaotropic ions could serve as stabilizing agents for non-ionic colloidal systems, such as non-ionic surfactant foams. EXPERIMENTS: We study foams of the non-ionic surfactant BrijO10 (C18:1E10) without and in presence of the superchaotropic Keggin-ion SiW12O404- (SiW). The foams are investigated under free drainage conditions by image analysis and conductimetry to reveal the effect of SiW on the foam stability, liquid drainage, and bubble size. Additionally, small angle neutron scattering on the same foams, but in a dry quasi-stationary state, provides insight into effects of SiW on the foam films. FINDINGS: SiW strongly stabilizes non-ionic surfactant foams at millimolar concentrations by inducing electrostatic repulsions between foam film interfaces resulting in thicker and monodisperse foam films. A similar effect is observed with the ionic surfactant sodium dodecylsulfate (SDS) but to a lesser extent and with a different mechanism. At the foam films' interface, SiW adsorbs to the polar non-ionic surfactant heads driven by the superchaotropic effect whereas DS- anchors between non-ionic surfactant alkyl chains by the hydrophobic effect. The potential of superchaotropic ions as foam stabilizers is herein demonstrated.

"Host in Host" Supramolecular Core-Shell Type Systems Based on Giant Ring-Shaped Polyoxometalates.

Herein, we show how the chaotropic effect arising from reduced molybdate ions in acidified aqueous solution is able to amplify drastically weak supramolecular interactions. Time-resolved Small Angle X-ray Scattering (SAXS) analysis suggests that molybdenum-blue oligomeric species form huge aggregates in the presence of γ-cyclodextrin (γ-CD) which results in the fast formation of nanoscopic {Mo154 }-based host-guest species, while X-ray diffraction analysis reveals that the ending-point of the scenario results in an unprecedented three-component well-ordered core-shell-like motif. A similar arrangement was found by using preformed hexarhenium chalcogenide-type cluster [Re6 Te8 (CN)6 ]4- as exogenous guest. This seminal work brings better understanding of the self-assembly processes in general and gives new opportunities for practical applications in the design of complex multicomponent materials via the simplicity of the non-covalent chemistry.

Self-assembly of a short amphiphile in water controlled by superchaotropic polyoxometalates: H4SiW12O40 vs. H3PW12O40.

Nanometric ions, such as polyoxometalates (POMs) or ionic boron clusters, with low charge density have previously shown a strong propensity to bind to macrocycles and to adsorb to neutral surfaces: micellar, surfactant covered water-air and polymer surfaces. These association phenomena were shown to arise from a solvent-mediated effect called the (super-)chaotropic effect. We show here by combining cloud point (CP) measurements, scattering (SAXS/SANS) and spectroscopic techniques (NMR) that Keggin POMs: H4SiW12O40 (SiW) and H3PW12O40 (PW), induce the self-assembly of an organic solvent: dipropylene glycol n-propylether (C3P2), in water. The strong interaction between SiW/PW with C3P2 leads to a drastic increase in the CP, and aqueous solubility, of C3P2, e.g. SiW enables reaching full water-C3P2 co-miscibility at room temperature. At high POM concentrations, SiW leads to a continuous increase of the CP, forming SiW-[C3P2]1-2 complexes, whereas PW produces a decrease in the CP attributed to the formation of nearly "dry" spherical [PW]n[C3P2]m colloids, with n ~ 4 and m ~ 30. At high C3P2/PW contents, the [PW]n[C3P2]m colloids turn into large interconnected structures, delimiting two pseudo-phases: a PW-C3P2-rich phase and a water-rich phase. It is proposed that the stronger electrostatic repulsions between SiW (4-), compared to PW (3-), prevents the formation of mesoscopic colloids.

Highlights on the Binding of Cobalta-Bis-(Dicarbollide) with Glucose Units.

Metalla-bis-dicarbollides, such as the cobalta-bis-dicarbollide (COSAN) anion [Co(C2 B9 H11 )2 ]- , have attracted much attention in biology but a deep understanding of their interactions with cell components is still missing. For this purpose, we studied the interactions of COSAN with the glucose moiety, which is ubiquitous at biological interfaces. Octyl-glucopyranoside surfactant (C8G1) was chosen as a model as it self-assembles in water and creates a hydrated glucose-covered interface. At low COSAN content and below the critical micellar concentration (CMC) of C8G1, COSAN binds to C8G1 monomers through the hydrophobic effect. Above the CMC of C8G1, COSAN adsorbs onto C8G1 micelles through the superchaotropic effect. At high COSAN concentrations, COSAN disrupts C8G1 micelles and the assemblies become similar to COSAN micelles but with a small amount of solubilized C8G1. Therefore, COSAN binds in a versatile way to C8G1 through either the hydrophobic or superchaotropic effect depending on their relative concentrations.

How Nano-Ions Act Like Ionic Surfactants.

Recently, nanometric ions were shown to adsorb to hydrated neutral surfaces and to bind to the cavities of macrocyclic molecules with an unexpectedly strong affinity arising from a solvent-mediated effect named superchaotropicity. We show here that nano-ions at low concentrations (µm range), similarly to anionic surfactants, induce the spontaneous transformation of a swollen lyotropic lamellar phase of non-ionic surfactant into a vesicle phase. This transition occurs when the neutral lamellae acquire charges, either by adsorption of the nano-ions onto, or by anchoring of the ionic surfactant into the lamellae. In contrast to ionic surfactants, nano-ions strongly dehydrate the neutral surfactant assemblies. As a conclusion, these purely inorganic nanometric ions act as alternatives to the widely used organic ionic surfactants.

Self-Assembly of Short Chain Poly- N-isopropylacrylamid Induced by Superchaotropic Keggin Polyoxometalates: From Globules to Sheets.

We show here for the first time that short chain poly( N-isopropylacrylamide) (PNIPAM), one of the most famous thermoresponsive polymers, self-assembles in water to form (i) discrete nanometer-globules and (ii) micrometric sheets with nm-thickness upon addition of the well-known Keggin-type polyoxometalate (POM) H3PW12O40 (PW). The type of self-assembly is controlled by PW concentration: at low PW concentrations, PW adsorbs on PNIPAM chains to form globules consisting of homogeneously distributed PWs in PNIPAM droplets of several nm in size. Upon further addition of PW, a phase transition from globules to micrometric sheets is observed for PNIPAMs above a polymer critical chain length, between 18 and 44 repeating units. The thickness of the sheets is controlled by the PNIPAM chain length, here from 44 to 88 repeating units. The PNIPAM sheets are electrostatically stabilized PWs accumulated on each side of the sheets. The shortest PNIPAM chain with 18 repeating units produces PNIPAM/PW globules with 5-20 nm size but no sheets. The PW/PNIPAM self-assembly arises from a solvent mediated mechanism associated with the partial dehydration of PW and of the PNIPAM, which is related to the general propensity of POMs to adsorb on neutral hydrated surfaces. This effect, known as superchaotropy, is further highlighted by the significant increase in the lower critical solubilization temperature (LCST) of PNIPAM observed upon the addition of PW in the mM range. The influence of the POM nature on the self-assembly of PNIPAM was also investigated by using H4SiW12O40 (SiW) and H3PMo12O40 (PMo), i.e. changing the POM's charge density or polarizability in order to get deeper understanding on the role of electrostatics and polarizability in the PNIPAM self-assembly process. We show here that the superchaotropic behavior of POMs with PNIPAM polymers enables the formation and the shape control of supramolecular organic-inorganic hybrids.

Ab initio prediction of structuring/mesoscale inhomogeneities in surfactant-free microemulsions and hydrogen-bonding-free microemulsions.

In this paper, we consider the influence of H-bond donor and acceptor functionalities on the formation of mesoscale inhomogeneities in ternary systems. It was found that hydrogen-bonding re-enforces such structures, but is not necessarily a prerequisite for the occurrence of mesoscale, microemulsion-like structuring in ternary surfactant-free microemulsions (SFME) and consequently, hydrogen-bonding-free microemulsions (HBFME) exist. The evaluated ternary systems were investigated by means of dynamic light scattering (DLS) and computer-based calculation methods. Theoretical COSMO-RS based calculations were applied to provide an explanation for different hydrotropic efficiencies, and COSMOplex calculations were used to predict and evaluate the propensity of the molecules to form mesoscale structures in SFME and HBFME. Microemulsion-like fluctuations could be observed in the COSMOplex simulations and correlate fairly well with the appearance of mesoscopic structures observed in SFME and HBFME, although the free energy differences in the formation of aggregate structures in the investigated systems are very small, in the range of 0.05 kcal mol-1.

Enzyme activity of horseradish peroxidase in surfactant-free microemulsions.

In the present contribution, we investigated the influence of the structuring of surfactant-free microemulsions (SFME) (water/1-propanol/limonene and water/tert-butanol/limonene) on the enzyme activity of horseradish peroxidase (HRP). To this purpose, the oxidation of 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) diammonium salt (ABTS) with hydrogen peroxide was chosen as a model reaction. Enzymatic activities in SFMEs of varying compositions were investigated by UV-Vis spectroscopy and compared to the enzyme activity in pure buffer solution. Dynamic light, small-angle-X-ray scattering and conductivity measurements were performed in order to obtain structural information on the used SFMEs. Findings presented in this study revealed that the ability of short-chain alcohols to form mesostructures (aqueous aggregates in oil) has a crucial effect on the enzyme activity in SFMEs. Mesoscale structuring with 1-propanol (NPA) was found to be more pronounced than for the more hydrophobic tert-butanol (TBA). It was concluded that the most pronounced mesoscale-structured SFMEs lead to the highest enzymatic activities.

Polyoxometalates in the Hofmeister series.

We propose a simple experimental procedure based on the cloud point measurement of a non-ionic surfactant as a tool for (i) estimating the super-chaotropic behaviour of polyoxometalates (POMs) and for (ii) establishing a classification of POMs according to their affinity towards polar surfaces.