Amphiphilic nonionic block and gradient copoly(2-oxazoline)s based on 2-methyl-2-oxazoline and 2-phenyl-2-oxazoline as efficient stabilizers for the formulation of tailor-made emulsions.

HYPOTHESIS: Poly(2-alkyl/aryl-oxazoline)s (PAOx) have seen a resurgence of interest in the new millennium due to their biocompatibility, low toxicity, and higher tunability compared to poly(ethylene glycol)s (PEG)s. Due to the straightforward access to hydrophilic and hydrophobic PAOx, it was hypothesized that amphiphilic PAOx should be capable of stabilizing oil/water (O/W) interfaces. Furthermore, the control of their composition, chain length, and monomer distribution could suggest the formulation of tunable emulsions. Special emphasis was given to evaluate whether spontaneously formed amphiphilic gradient copolymer could stabilize O/W emulsions. EXPERIMENTS: We prepared a series of amphiphilic block and gradient copolymers based on 2-methyl-2-oxazoline and 2-phenyl-2-oxazoline with variable hydrophilic/lipophilic balance, degree of polymerization, and monomer distribution as basis to explore their ability to stabilize emulsions. Systematic granulometry, stability, and rheology studies were performed to characterize the final emulsions. FINDINGS: Remarkably, stable O/W emulsions are obtained with only 0.5 wt% of copolymers. The finer emulsions stabilized by the most hydrophilic copoly(2-oxazoline)s allow an adjustment of their texture, as well as the concentration increase and oil content. Importantly, emulsion properties prepared with gradient copolymers show similar behavior compared with their block counterparts offering easy access to new biocompatible emulsifiers as these gradient copolymers are spontaneously formed by statistical copolymerization.

A New Synergistic Strategy for Virus and Bacteria Eradication: Towards Universal Disinfectants.

In response to the COVID-19 and monkeypox outbreaks, we present the development of a universal disinfectant to avoid the spread of infectious viral diseases through contact with contaminated surfaces. The sanitizer, based on didecyldimethylammonium chloride (DDAC), N,N-bis(3-aminopropyl)dodecylamine (APDA) and γ-cyclodextrin (γ-CD), shows synergistic effects against non-enveloped viruses (poliovirus type 1 and murine norovirus) according to the EN 14476 standard (≥99.99% reduction of virus titer). When a disinfectant product is effective against them, it can be considered that it will be effective against all types of viruses, including enveloped viruses. Consequently, "general virucidal activity" can be claimed. Moreover, we have extended this synergistic action to bacteria (P. aeruginosa, EN 13727). Based on physicochemical investigations, we have proposed two independent mechanisms of action against bacteria and non-enveloped viruses, operating at sub- and super-micellar concentrations, respectively. This synergistic mixture could then be highly helpful as a universal disinfectant to avoid the spread of infectious viral or bacterial diseases in community settings, including COVID-19 and monkeypox (caused by enveloped viruses).

From polyethyleneimine hydrogels to Pickering-like smart "On/Off" emulgels switched by pH and temperature.

HYPOTHESIS: According to the so-called colloidal tectonic concept, we assumed that a single self-complementary polymer-based tecton could be used to design self-assembled emulsions. The polymer must be of high-molecular weight with balanced bipolar properties generating those of rigidity and flexibility. Linear polyethyleneimine (LPEI, 25 kDa) was used because it acts as a buffer by continuous protonation/deprotonation of the amine groups. EXPERIMENTS: The relationships between the physicochemical properties of LPEI (protonation, charge, size, aggregation and gelation) and emulsions (type, droplet size, rheological behavior and stability) were investigated to highlight the self-assembly and stabilization mechanisms during the construction events as well as the inherent properties of emulsions (responsiveness to external stimuli). FINDINGS: In aqueous solution, after a first heat and cool cycle, the adequate and spontaneous self-assembly of hydrophobic and hydrophilic sections leads to hydrogels by the formation of a 3D network where the crystallized hydrophobic domains act as knots. In the presence of various oils, the hydrogels provide long-term stable Pickering emulgels. The as-prepared emulsions are highly controllable due to their self-assembled nature (up to 10 consecutive runs). Consequently, this new approach provides a facile route to construct self-assembled, reversible and dynamics Pickering-like emulsions by simplifying the colloidal tectonics concept.

Multiphase Microreactors Based on Liquid-Liquid and Gas-Liquid Dispersions Stabilized by Colloidal Catalytic Particles.

Pickering emulsions, foams, bubbles, and marbles are dispersions of two immiscible liquids or of a liquid and a gas stabilized by surface-active colloidal particles. These systems can be used for engineering liquid-liquid-solid and gas-liquid-solid microreactors for multiphase reactions. They constitute original platforms for reengineering multiphase reactors towards a higher degree of sustainability. This Review provides a systematic overview on the recent progress of liquid-liquid and gas-liquid dispersions stabilized by solid particles as microreactors for engineering eco-efficient reactions, with emphasis on biobased reagents. Physicochemical driving parameters, challenges, and strategies to (de)stabilize dispersions for product recovery/catalyst recycling are discussed. Advanced concepts such as cascade and continuous flow reactions, compartmentalization of incompatible reagents, and multiscale computational methods for accelerating particle discovery are also addressed.

Highly Active, Entirely Biobased Antimicrobial Pickering Emulsions.

We present the development of surfactant-free, silica-free and fully biobased oil-in-water antimicrobial Pickering emulsions, based on the self-assembly of ß-cyclodextrin and phytoantimicrobial oils (terpinen-4-ol or carvacrol). Undecylenic acid (UA), derived from castor oil, can be used as bio-based drug to treat fungal infection, but is less effective than petroleum-based drugs as azole derivatives. To maximize its antifungal potential, we have incorporated UA in fully biobased Pickering emulsions. These emulsions are effective against fungi, Gram-positive and Gram-negative bacteria. The carvacrol emulsion charged with UA is +390 % and +165 % more potent against methicillin-resistant S. aureus (MRSA), compared to UA and azole-based commercial formulations. Moreover, this emulsion is up to +480 % more efficient that UA ointment against C. albicans. Finally, remarkable eradication of E. coli and MRSA biofilms was obtained with this environmental-friendly emulsion.

How to improve the chemical disinfection of contaminated surfaces by viruses, bacteria and fungus?

In response to the current pandemic situation, we present the development of an effective virucidal and biocidal solution to prevent from the spread of infectious diseases through contact with contaminated surfaces. The disinfectants, based on equimolar mixtures of didecyldimethylammonium chloride ([DiC10][Cl]), dodecyloctaglycol (C12E8), and cyclodextrin (CD), show synergistic effects against enveloped viruses (RSV, HSV-1, VACV) and fungi (C. albicans), and additive responses against bacteria (P. aeruginosa). These synergistic mixtures could then be highly helpful for prevention of respiratory illnesses, since a boosted activity allows: (i) a faster eradication of pathogens, (ii) a shorter contact time, and (iii) a complete and broad-spectrum eradication to avoid spread of resistant strains (including bacteria and fungi).

Phytochemical- and Cyclodextrin-Based Pickering Emulsions: Natural Potentiators of Antibacterial, Antifungal, and Antibiofilm Activity.

We present self-assembled Pickering emulsions containing biocidal phytochemical oils (carvacrol and terpinen-4-ol) and ß-cyclodextrin able to potentiate the antimicrobial and antibiofilm activity of miconazoctylium bromide. The carvacrol-containing emulsion is 2-fold more sensitive against C. albicans and S. aureus and highly active against E. coli, compared to the commercial cream containing miconazole nitrate. Moreover, this emulsion shows a synergistic effect against fungi, additive responses against bacteria, and remarkable staphylococcal biofilm eradication. These results are associated with membrane permeabilization, enzymes inhibition, and the accumulation of reactive oxygen species in microorganisms.

Colloidal tectonics for tandem synergistic Pickering interfacial catalysis: oxidative cleavage of cyclohexene oxide into adipic acid.

Supramolecular preorganization and interfacial recognition can provide useful architectures for colloidal building. To this aim, a novel approach, based on colloidal tectonics involving two surface-active particles containing both recognition and catalytic sites, has been developed for controlling the formation and the properties of Pickering emulsions. This was illustrated by the combination of dodecyltrimethylammonium phosphotungstate nanoparticles, [C12]3[PW12O40], and silica particles functionalized with alkyl and sulfonic acid groups, [C n /SO3H]@SiO2. The interfacial self-assembly occurs by the penetration of the alkyl chains of [C n /SO3H]@SiO2 into the [C12]3[PW12O40] supramolecular porous structure constituted of polar and apolar regions. The emulsions were used as a non-nitric acid route for adipic acid synthesis from the one-pot oxidative cleavage of cyclohexene oxide with aqueous H2O2. The catalytic performance was significantly boosted due to the synergistic interactions between the particles.

Hybrid Core-Shell Nanoparticles by "Plug and Play" Self-Assembly.

Supramolecular hybrid functional nanoparticles (NPs) can be obtained via the colloidal tectonics approach provided that multiple interactive molecular tectons are used. Herein, the programmable synthesis of novel hybrid core-shell nanoparticles via the following sequential steps is reported: (i) complexation of 1-decanol by the ß-cyclodextrin (ß-CD), (ii) spontaneous self-assembly into CD NPs, (iii) adsorption of polyoxometalate anions, PW12 O40 3- , on the polar neutral interface of the CD NPs. Such an approach paves the way for the design of novel and original materials and systems.

Get Beyond Limits: From Colloidal Tectonics Concept to the Engineering of Eco-Friendly Catalytic Systems.

The interactions between two or more molecules or colloidal particles can be used to obtain a variety of self-assembled systems called supramolecules or supracolloids. There is a clear, but neglected, convergence between these two fields. Indeed, the packing of molecules into colloidal or supracolloidal particles emerges as a smart solution to build an infinite variety of reversible systems with predictable properties. In this respect, the molecular building blocks are called "tectons" whereas "colloidal tectonics" describes the spontaneous formation of (supra)colloidal structures using tectonic subunits. As a consequence, a bottom-up edification is allowed from tectons into (supra)colloidal particles with higher degrees of organization (Graphical Abstract). These (supra)colloidal systems can be very useful to obtain catalysts with tunable amphiphilic properties. In this perspective, an overview of colloidal tectonics concept is presented as well as its use for the design of new, smart, and flexible catalytic systems. Finally, the advantages of these catalytic devices are discussed and the perspective of future developments is addressed especially in the context of "green chemistry."

Supramolecular "Big Bang" in a Single-Ionic Surfactant/Water System Driven by Electrostatic Repulsion: From Vesicles to Micelles.

In aqueous solution, dimethyldi-n-octylammonium chloride, [DiC8][Cl], spontaneously forms dimers at low concentrations (1-10 mM) to decrease the strength of the hydrophobic-water contact. Dimers represent ideal building blocks for the abrupt edification of vesicles at 10 mM. These vesicles are fully characterized by dynamic and static light scattering, self-diffusion nuclear magnetic resonance, and freeze-fracture transmission electron microscopy. An increase in concentration leads to electrostatic repulsion between vesicles that explode into small micelles at 30 mM. These transitions are detected by means of surface tension, conductivity, and solubility of hydrophobic solutes as well as by isothermal titration microcalorimetry. These unusual supramolecular transitions emerge from the surfactant chemical structure that combines two contradictory features: (i) the double-chain structure tending to form low planar aggregates with low water solubility and (ii) the relatively short chains giving high hydrophilicity. The well-balanced hydrophilic-hydrophobic character of [DiC8][Cl] is then believed to be at the origin of the unusual supramolecular sequence offering new opportunities for drug delivery systems.

Supramolecular assistance between cyclodextrins and didecyldimethylammonium chloride against enveloped viruses: Toward eco-biocidal formulations.

Nosocomial infections have emerged as important causes of morbidity and mortality in immunocompromised individuals. In this respect, biocides are widely used in hospitals leading to resistant microorganisms. We show here that cyclodextrins can remarkably boost the virucidal activity of di-n-decyldimethylammonium chloride. These oligosaccharides synergistically work with the biocide affording a noticeable reduction of the active virucide concentration between 40 and 85%. Partial replacement of a significant amount of the biocide by eco- and bio-compatible cyclodextrins whilst maintaining the same activity is of great interest as it allows the reduction of the toxicological drawbacks of classical biocide mixtures.

Aqueous solutions of didecyldimethylammonium chloride and octaethylene glycol monododecyl ether: Toward synergistic formulations against enveloped viruses.

Micellization of di-n-decyldimethylammonium chloride, [DiC10][Cl], and octaethylene glycol monododecyl ether, C12E8, mixtures have been investigated by surface tension and conductivity measurements. From these results, various physicochemical and thermodynamic key parameters (e.g. micellar mole fraction of [DiC10][Cl], interaction parameter, free energy of micellization, etc.) have been evaluated and discussed in detail. The results prove high synergistic effect between the two surfactants. Based on these results, the virucidal activity of an equimolar mixture of [DiC10][Cl] and C12E8 has been investigated. A marked synergism was observed on lipid-containing deoxyribonucleic and ribonucleic acid viruses, such as herpes virus, respiratory syncytial virus, and vaccinia viruses. In contrast, Coxsackievirus (non-enveloped virus) was not inactivated. These results support that the mechanism is based on the extraction of lipids and/or proteins from the envelope inside the mixed micelles. This extraction creates "holes" the size of which increases with concentration up to a specific value which triggers the virus inactivation. Such a mixture could be used to extend the spectrum of virucidal activity of the amphiphiles virucides commonly employed in numerous disinfectant solutions.

Interactions between cyclodextrins and cellular components: Towards greener medical applications?

In the field of host-guest chemistry, some of the most widely used hosts are probably cyclodextrins (CDs). As CDs are able to increase the water solubility of numerous drugs by inclusion into their hydrophobic cavity, they have been widespread used to develop numerous pharmaceutical formulations. Nevertheless, CDs are also able to interact with endogenous substances that originate from an organism, tissue or cell. These interactions can be useful for a vast array of topics including cholesterol manipulation, treatment of Alzheimer's disease, control of pathogens, etc. In addition, the use of natural CDs offers the great advantage of avoiding or reducing the use of common petroleum-sourced drugs. In this paper, the general features and applications of CDs have been reviewed as well as their interactions with isolated biomolecules leading to the formation of inclusion or exclusion complexes. Finally, some potential medical applications are highlighted throughout several examples.

[Guislain Decrombecque (1797-1870) and Alfred Wagon (1849-1928) originally of Auguste Béhal career (1859-1941)?]

Auguste Béhal (1859-1941), Maître de Conférences (Assistant Professor) at the Sorbonne then Full Professor at the School of Pharmacy (Paris), leads many vocations among these students (Blaise, Delaby, Delepine, Detoeuf, Fourneau, Sommelet, Tiffeneau, Valeur, etc.). However, why is he embraced the vocation chemist organic chemist ? This choice is undoubtedly dictated by the meeting of Adolphe Wurtz (1817-1884) and Charles Friedel (1832-1899) who made mature in him a passion for chemical research during his formation. Nevertheless, the historical context of the city of Lens, a modest city of 2.500 inhabitants in the north of France, and the influence of two other characters : Guislain Decrombecque (1797-1870), agronomist, and Alfred Wagon (1849-1928), 2nd class pharmacist, are also noteworthy. We will outline how these two people have directly and indirectly contributed to the Béhal career.

Pickering emulsions based on cyclodextrins: A smart solution for antifungal azole derivatives topical delivery.

Surfactants are usually used for the preparation of emulsions. Potential drawbacks on the human body or on the environment can be observed for some of them(e.g. skin irritation, hemolysis, protein denaturation, etc.). However, it is possible to use biocompatible emulsifiers such as native cyclodextrins (CDs). The mixture of oil (paraffin oil or isopropyl myristate), water and native CDs results in the formation of Pickering emulsions. The emulsion properties were investigated by ternary phase diagrams elaboration, multiple light scattering, optical and transmission microscopies. The results prove that these Pickering emulsions were very stable against coalescence due to the dense film format the oil/water interface. The rheological behavior has shown that these emulsions remain compatible for topical applications. This kind of emulsions (biocompatibility, stability and surfactant free) has been used to obtain sustainable formulations for antifungal econazole derivatives delivery. Our results prove that these new formulations are at least as active as commercially available formulations.

Self-assembled polyoxometalates nanoparticles as pickering emulsion stabilizers.

We easily produced a series of polyoxometalate (POM) nanoparticles by taking benefit from electrostatic attractions between various POMs and alkylammonium cations. These self-assembled supramolecular nanoparticles are fully characterized in terms of shape, nanostructure, and physicochemical properties. The nanoparticle differences are discussed on the basis of the chemical composition of the initial POM. Moreover, such particles have the ability to stabilize water-in-oil Pickering emulsions. Using a gel-trapping technique coupled to atomic force microscopy (AFM) observations, we determined their affinity toward oil by the contact angle of adsorbed nanoparticles. We show that the emulsion droplet size and stability can be directly linked to the nanoparticle hydrophobicity, which is tuned by the charge localization and molecular packing of POMs with the ammonium cations. Such particles are of special interest as they open large possibilities for Pickering interfacial catalysis.

Pickering interfacial catalysis for biphasic systems: from emulsion design to green reactions.

Pickering emulsions are surfactant-free dispersions of two immiscible fluids that are kinetically stabilized by colloidal particles. For ecological reasons, these systems have undergone a resurgence of interest to mitigate the use of synthetic surfactants and solvents. Moreover, the use of colloidal particles as stabilizers provides emulsions with original properties compared to surfactant-stabilized emulsions, microemulsions, and micellar systems. Despite these specific advantages, the application of Pickering emulsions to catalysis has been rarely explored. This Minireview describes very recent examples of hybrid and composite amphiphilic materials for the design of interfacial catalysts in Pickering emulsions with special emphasis on their assets and challenges for industrially relevant biphasic reactions in fine chemistry, biofuel upgrading, and depollution.

Supramolecular colloidosomes based on tri(dodecyltrimethylammonium) phosphotungstate: a bottom-up approach.

Hybrid tri(dodecyldimethylammonium) phosphotungstate ([C12]3[PW12O40]) amphiphilic nanoparticles self-assemble in situ at the water/toluene interface to form stable water-in-oil (W/O) Pickering emulsions (droplet size ≈ 20 µm). These emulsions are used as a template for the preparation of colloidosomes (ϕ ≈ 5 µm), which are produced solely through the self-assembly properties of the [C12]3[PW12O40] nanoparticles into a "fused" phase on the water-drop surface in contact with toluene. The structure of the emulsions has been determined using optical and cross-polarized light microscopy, while the colloidosomes have been characterized by scanning electron microscopy (SEM). The structure as well as the aggregation behavior of these nanoparticles has been investigated. Small- and wide-angle X-ray scattering (SWAXS) and transmission electron microscopy (TEM) experiments have revealed a lamellar organization of the inorganic polyoxometalate anions because of the van der Waals interactions between the alkyl chains of the organic cations. According to the solvent, the internal molecular arrangement inside the nanoparticles can be modified: in water, the nanoparticles tend to aggregate in a lamellar structure, whereas in toluene, the nanoparticles are "fused" or coagulated.

Encapsulation of biocides by cyclodextrins: toward synergistic effects against pathogens.

Host-guest chemistry is useful for the construction of nanosized objects. Some of the widely used hosts are probably the cyclodextrins (CDs). CDs can form water-soluble complexes with numerous hydrophobic compounds. They have been widespread used in medicine, drug delivery and are of interest for the biocides encapsulation. Indeed, this enables the development of more or less complex systems that release antimicrobial agents with time. In this paper, the general features of CDs and their applications in the field of biocides have been reviewed. As the key point is the formation of biocide-CD inclusion complexes, this review deals with this in depth and the advantages of biocide encapsulation are highlighted throughout several examples from the literature. Finally, some future directions of investigation have been proposed. We hope that scientists studying biocide applications receive inspiration from this review to exploit the opportunities offered by CDs in their respective research areas.