Synergistic topological and supramolecular control of Diels-Alder reactivity based on a tunable self-complexing hos-guest molecular switch

International audienceCompartmentalization and binding‐triggered conformational change regulate many metabolic processes in living matter. Here, we have synergistically combined these two biorelevant processes to tune the Diels‐Alder (DA) reactivity of a synthetic self‐complexing host‐guest molecular switch CBPQT4+‐Fu, consisting of an electron‐rich furan unit covalently attached to the electron‐deficient cyclobis(paraquat‐p‐phenylene) tetrachloride (CBPQT4+, 4Cl‐) host. This design allows CBPQT4+‐Fu to efficiently compartmentalize the furan ring inside its host cavity in water, thereby protecting it from the DA reaction with maleimide. Remarkably, the self‐complexed CBPQT4+‐Fu can undergo a conformational change through intramolecular decomplexation upon the addition of a stronger binding molecular naphthalene derivative as a competitive guest, triggering the DA reaction upon addition of a chemical regulator. Remarkably, connecting the guest onto a thermoresponsive lower critical solution temperature (LCST) copolymer regulator controls the DA reaction on command upon heating and cooling the reaction media beyond and below the cloud point temperature of the copolymer, representing a rare example of decreased reactivity upon increasing temperature. Altogether, this work opens up new avenues towards combined topological and supramolecular control over reactivity in synthetic constructs enabling control over reactivity through molecular regulators or even mild temperature variations

Copolymers based on azidopentyl-2-oxazoline: Synthesis, characterization and LCST behavior

International audienceReactive polymers based on 2-(5-azidopenty1)-2-oxazoline (N(3)PentOx) were prepared. This N3PentOx monomer should be used to create a platform for the design of polyoxazoline based polymers with original architecture or polymer drug conjugates. The poly(2-(5-azido penty1)-2-oxazoline) were synthesized by cationic ring-opening polymerization (CROP). A kinetic study was performed to demonstrate a good control over the polymerization of this functional oxazoline monomer. The polymerization constant was comparable to those reported for 2-methyl-2-oxazoline (PMeOx). Well-defined poly(2-methy1-2-oxazoline-co-2-(5-azidopenty1)-2-oxazoline) with low dispersity were prepared and characterized by FTIR spectroscopy, NMR spectroscopy and size exclusion chromatography. The reactivity ratios (T-MeOx.= 1.73 and rN(3PentOx) = 0.71) of each monomer were determined, indicating a slight compositional heterogeneity in the synthesized quasi-statistical copolymers. Although PMeOx is known to have no LCST, the copolymers with small amount of N(3)PentOx presented a lower critical solution temperature (LCST) behavior depending on molecular weights and composition of the copolymers

Self-assembly of poly(2-alkyl-2-oxazoline-)-g-poly(d,l-lactide) copolymers

International audienceIn this article, is reported for the first time the preparation of nanoparticles from graft copolymer composed of a hydrophilic backbone made of poly(2-methyl-2-oxazoline-co-2-pentyl-2-oxazoline) and hydrophobic poly(d,l-lactide) grafts. The copolymers were synthesized by the grafting-onto approach through the Huisgen 1,3-dipolar cycloaddition reaction. The success of the reaction was confirmed by H-1 NMR, FTIR and thermogravimetric analysis (TGA). Different copolymers were prepared from two molecular weight backbones (5.7 x 10(3) and 14.2 x 10(3) g mo1(-1)) giving graft copolymers with molecular weight in the range of 3.7 x 10(4) to 113 x 10(4) g mo1(-1). These copolymers self-assembled to form nanoparticles in water. Nanoparticles of spherical shape and various morphologies, going from polymersomes to core-shell and homogenous spherical nano-objects, were imaged by cryo-transmission electron microscopy (cryo-TEM) and analyzed by dynamic light scattering (DLS) and small -angle neutron scattering (SANS

Amphiphilic diblock and triblock copolymers based on poly(2-methyl-2-oxazoline) and poly(D,L-lactide): Synthesis, physicochemical characterizations and self-assembly properties

International audienceA range of amphiphilic diblock and triblock copolymers based on poly (2-methyl-2-oxazoline) (PMeOx) and poly (D, L-lactide) (PLA) with various compositions and molecular masses were prepared combining cationic ringopening polymerization and click chemistry. Their hydrophilic weight ratios (f) covered a wide range of composition (21-77%). In water, these amphiphilic copolymers self-assembled to form, in the case of diblock copolymers, core-shell micellar structures with a dense PLA core and a hydrated PMeOx shell in the whole range of f values. The triblock copolymers formed micellar aggregates of finite sizes made of bridged micelles, the micelles being connected by some of the PLA end-blocks. Moreover, the micelles displayed original core-multishell nanostructures in a specific range of f values (48%), never reported for this kind of triblock copolymers. The amphiphilic copolymers of this study displayed a rich variety of controlled self-assembled morphologies which could be promising candidates for drug delivery applications

Self-Assembly of Stimuli-Responsive Biohybrid Synthetic-b-Recombinant Block Copolypeptides

The synthesis and original thermoresponsive behavior of hybrid diblock copolypeptides composed of synthetic and recombinant polypeptides are herein reported. A thermoresponsive recombinant elastin-like polypeptide was used as a macroinitiator to synthesize a range of poly(L-glutamic acid)-block-elastin-like polypeptide (PGlu-b-ELP) diblock copoly-peptides with variable PGlu block lengths. Their temperature-triggered self-assembly in water and in phosphate-buffered saline (PBS) was investigated at the macroscopic scale using complementary techniques such as turbidimetry, dynamic and static light scattering, small-angle neutron scattering, and at the molecular scale by 1 H NMR and circular dichroism (CD). In deionized water, PGlu-b-ELP copolypeptides showed one transition from free soluble chains below the transition temperature (Tt) of the ELP block to macroscopic aggregates above the Tt. In contrast, in PBS, four successive regimes were observed upon increasing temperature: below the Tt , copolypeptides were soluble, above the Tt , large aggregates appeared and fell apart into discrete and defined spherical nanoparticles at a temperature named critical micellization temperature (CMT), before finally reaching an equilibrium. During the last regime, neutron scattering experiments revealed that the micelle-like structures underwent a densification step and expelled water from their core. In addition, 1H NMR and CD experiments revealed, in deionized water, the formation of type II β-turns into the ELP block upon temperature increase. These β-turns are known to participate in the intrinsic thermoresponsive behavior of the ELPs. In contrast, in PBS, circular dichroism measurements showed an attenuation of folded structure during the self-assembly phase, leading to less cohesive aggregates able to reorganize into nanoparticles at the CMT

An Efficient Thiol-Ene Chemistry for the Preparation of Amphiphilic PHA-Based Graft Copolymers

International audienceWe present a straightforward method to prepare amphiphilic graft copolymers consisting of hydrophobic poly(3-hydroxyalkanoates) (PHAs) backbone and hydrophilic a-amino-?-methoxy poly(oxyethylene-co-oxypropylene) (Jeffamine (R)) units. Poly(3-hydroxyoctanoate)-co-(3-hydroxyundecenoate) (PHOU) was first methanolyzed to obtain the desired molar mass. The amino end groups of Jeffamine were converted into thiol by a reaction with N-acetylhomocysteine thiolactone and subsequently photografted. This one-pot functionalization prevents from arduous and time-consuming functionalization of the hydrophilic precursor or tedious modifications of PHAs, thus simplifying the process. The amphiphilic nature of modified PHAs leads to water-soluble copolymers exhibiting thermoresponsive behavior

Chemo-enzymatic synthesis of glycolipids, their polymerization and self-assembly

This paper describes the synthesis of bio-based methacrylated 12-hydroxystearate glucose (MASG), and its (co)polymerization with methyl methacrylate (MMA) by either free-or RAFT radical polymerizations. The obtained amphiphilic p(MMA-MASG) copolymers self-assembled in water into various morphologies depending on the MASG unit content and glycopolymer crystallinity. Finally, as a proof of concept, a hydrophobic dye, Nile Red, was entrapped by co-nanoprecipitation into p(MMA-MASG) nanoparticles, showing their loading capacity and thus demonstrating the potential of such amphiphilic glycolipid-based copolymers in hydrophobic compound encapsulation applications

Robust Polyion Complex Vesicles (PICsomes) Based on PEO-b-poly(amino acid) Copolymers Combining Electrostatic and Hydrophobic Interactions: Formation, siRNA Loading and Intracellular Delivery

Two pairs of oppositely charged PEO-b-poly(amino acid) copolymers with neutral poly(ethylene oxide) block and polypeptide block composed of the hydrophobic l-phenylalanine (Phe) amino acid mixed with either negative l-glutamic acid (Glu) or positive l-lysine (Lys) units are synthesized. N-carboxyanhydride (NCA) ring opening polymerization is performed with either PEO46-NH2 or PEO114-NH2 macroinitiators, leading respectively to PEO46-b-P(Glu100-co-Phe65) and PEO46-b-P(Lys100-co-Phe65), and PEO114-b-P(Glu60-co-Phe40) and PEO114-b-P(Lys60-co-Phe40). Polyion complexes (PIC) formed at near charge equilibrium led to vesicle formation (PICsomes), as shown by DLS, zetametry, and TEM. The good stability of PICsomes, even in high salinity media, is interpreted by π π stacking hydrophobic interactions between the Phe residues, playing the role of “physical cross-linking”. These PICsomes are successfully loaded with small interfering ribonucleic acid (siRNA) directed against firefly luciferase enzyme expression. They also exhibit minimal cell cytotoxicity while superior silencing efficacy is shown by cell bioluminescence assay as compared to free siRNA and a standard lipofectamine-siRNA complex. As such, self-assembly of oppositely charged PEO-b-poly(amino acids) block copolymers enables forming PICsomes of high stability thanks to π π interactions of the Phe co-monomer in the polypeptide block, with high potential as biocompatible nanocarriers for RNA interference

Light sensitive synthesis of 2D COF imine particles

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Synergetic synthesis of colloidal “Covalent Organic Frameworks-Polymers”

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