Polyplexes prepared from DNA and globular compact polycationic derivatives constructed around a fullerene hexakis-adduct core have shown remarkable gene delivery capabilities.

Cationic surfactants easily interact with plasmid DNA to form small lipoplexes. However, their detergent behavior and associated biological toxicity limit their use as gene delivery vectors. We have incorporated a diacetylene motif in the hydrophobic chain of cationic surfactants. By using UV irradiation, the small cationic micelles (9 nm) obtained with diacetylenic detergents were photopolymerized into 40 nm spheres. Electrostatic interactions with plasmid DNA led to the formation of 45 nm lipoplexes at N/P = 5 ratio. In vitro transfection of the pCMV-Luciferase plasmid resulted in gene expression (>10(10) RLU/mg protein) at the same ratio, comparable with the commercially available JetSi-ENDO gene delivery system. This new and versatile class of molecules could lead to a new generation of in vivo gene delivery vectors.

Iron chelation in tumoral cells has been reported as potentially useful during antitumoral treatment. Our aim was to develop new polyaminoquinoline iron chelators targeting tumoral cells. For this purpose, we designed, synthesized, and evaluated the biological activity of a new generation of iron chelators, which we named Quilamines, based on an 8-hydroxyquinoline (8-HQ) scaffold linked to linear polyamine vectors. These were designed to target tumor cells expressing an overactive polyamine transport system (PTS). A set of Quilamines bearing variable polyamine chains was designed and assessed for their ability to interact with iron. Quilamines were also screened for their cytostatic/cytotoxic effects and their selective uptake by the PTS in the CHO cell line. Our results show that both the 8-HQ moiety and the polyamine part participate in the iron coordination. HQ1-44, the most promising Quilamine identified, presents a homospermidine moiety and was shown to be highly taken up by the PTS and to display an efficient antiproliferative activity that occurred in the micromolar range. In addition, cytotoxicity was only observed at concentrations higher than 100 μM. We also demonstrated the high complexation capacity of HQ1-44 with iron while much weaker complexes were formed with other cations, indicative of a high selectivity. We applied the density functional theory to study the binding energy and the electronic structure of prototypical iron(III)-Quilamine complexes. On the basis of these calculations, Quilamine HQ1-44 is a strong tridentate ligand for iron(III) especially in the form of a 1:2 complex.

We describe a general user-friendly platform for fine-tuning the drug release properties of low-molecular-weight hydrogels by a combination of supramolecular co-assembly of complementary molecular structures and controlled photochemical thiol-ene cross-linking.Other critical features such as thermomechanical stability and morphology of the nanostructured hydrogels are also tailored by this approach.Molecular functional gels able to immobilize a large number of solvent molecules have been a subject of study for well over a century. 1 These hierarchical, self-assembled, and viscoelastic materials may be considered to be either hard or soft based on their rheological characteristics, 2 and can be categorized into two major types according to their driving forces for molecular aggregation: chemical gels, 3 based on covalent bonds, and physical gels, 1,4 based on non-covalent bonds. 'Bottom-up' processing of stable and stimuliresponsive gels has allowed their use in important applications (e.g. regenerative medicine, sensors, nanoelectronics, etc.). 5 Nevertheless, the search for a universal platform to fine-tune their functional properties, especially in the case of gels made of low-molecularweight-gelators (LMWGs), continues being a great scientific challenge for the creation of shape-controlled and robust functional soft-materials. 6-8 On the other hand, Sharpless and co-workers introduced, early in this decade, the valuable concept of 'click' chemistry, 9 exemplified by the copper(I)-catalyzed azide-alkyne cycloaddition (CuAAC). 10 After the first 'boom' caused by the versatility of the CuAAC, 11 the century-old thiol-ene coupling (TEC) 12 has emerged as a competitive orthogonal strategy for the high-yield synthesis of complex functional networks under mild conditions. 13,14 In this communication, we report the supramolecular co-assembly (SMCA) of complementary structures followed by controlled TEC as a new user-friendly strategy for fine-tuning the drug release kinetics of self-assembled hydrogels made of LMWGs. In addition, its effect on the sol-to-gel transition temperature (T gel ) and morphology of the materials is also described.The hydrogelation ability of LMW hydrogelator dibenzoyl-L-cystine (1) at very low concentrations (0.2 wt%) was already noted in 1892 15 and revisited by Menger and Caran in the late 90's. 16 The gelation phenomenon is driven here by a favorable backbone orientation (CH 2 -S-S-CH 2 dihedral angle $87 to 99 ) enhanced by cooperative hydrogen-bonding and p-p stacking interactions (Fig. 1). Inspired by our previous studies directed towards the mechanical stabilization of organogels via CuAAC, 17 pseudocomplementary compounds 2-4 were synthesized by incorporation of terminal alkene units. 18 In contrast to other LMWGs, 19 the simple co-assembly process of LMWG 1 at 0.2 wt% in water with the corresponding alkene-containing analogues 2, 3 or 4 (under optimized molar ratio 1 : (2-4) ¼ 10 : 1) did not improve the mechanical strength of the fragile original hydrogel. 18 The stability of the h...

N-Methyl-N-(pentacosa-10,12-diyn)-propargylamine organizes itself into an unusual supramolecular pH- and thermo-responsive system. Studies have showed that submillimetric length hollow laths form this unique structure in the presence of hydrochloric acid. Specific chemical modifications on the initial molecule and small-angle neutron scattering experiments were performed to understand the structure of this system. Our results allow us to suggest a possible structure of the laths.

Amphiphiles are known to be suitable molecules to disperse carbon nanotubes (CNTs) in water by shielding their highly hydrophobic surfaces. Herein, we describe tailored anionic, nonionic, and cationic photopolymerizable synthetic amphiphiles that are designed to achieve programmed pH-dependent dispersions of CNTs. The reported process involves (1) the assessment of the amphiphiles’ ability to form micelles in given buffer solutions, (2) the equilibrated self-assembly of the amphiphiles into hemimicellar structures on the hydrophobic surface of the CNTs, (3) the stabilization of these labile supramolecular assemblies by photopolymerization, (4) the purification of the obtained CNTs/photopolymerized lipidic assemblies (PLA) constructs, and (5) the characterization of the CNTs/PLA constructs pH dependant dispersion. In conclusion, we demonstrate that CNTs/PLA constructs with specific pH-dependent dispersion properties can easily be prepared. The constructs appear quite robust because they can withstand several cycles of precipitation and redispersion, and interestingly, they demonstrate the same pH-dependency as the amphiphiles used in the coating process.