Cyril Bourgogne

Mesomorphic imidazolium salts: new vectors for efficient siRNA transfection.

The preparation of chloride (1(n)) and bromide (2(n)) derivatives of 1-methyl-3-[3,4-bis(alkoxy)benzyl]-4H-imidazolium with n = 6, 12, 16, 18 is described. The two series of salts possess a rich thermotropic mesomorphism, chain-length dependent. Thus, a lamellar smectic A phase, a bicontinuous cubic Ia3d phase, and a columnar hexagonal liquid crystalline mesophase are induced as a function of increasing chain length. The mesomorphic properties were studied by polarizing optical microscopy, differential scanning calorimetry, and X-ray diffraction, and with the support of dilatometry and molecular dynamics, models for the various supramolecular arrangements of the salts are proposed. Such cationic amphiphiles were expected to be candidate molecules to design a new delivery reagent for nucleic acid transfection, particularly for short interfering RNA (siRNA). The use of an RNA interference mechanism, by introduction into cells by transfection of chemically synthesized siRNAs, is a powerful method for gene silencing studies. To exploit the potential of these amphilic imidazolium salts, these molecules were formulated with cohelper lipids and tested for their efficacy to deliver active siRNAs. Our results show high transfection efficacy of our formulated compounds and high silencing efficiency with more than 80% inhibition of the targeted gene at 10 nM siRNA concentration. Taken together our results show the potency of amphiphilic imidazolium salts as a new generation of transfection reagents for RNA interference.

Molecular Engineering of Photoremovable Protecting Groups for Two-Photon Uncaging†

The photochemical release of theactive molecule is usually induced by an initial one-photonabsorption process, leading to a limited spatial localization ofthe released substance. To overcome this obstacle, two-photon (TP) excitation has recently emerged as a verypromising technique to obtain spatial control.

A supramolecular cup-and-ball C60-porphyrin conjugate system

In addition to the ammonium-crown ether recognition, pi-stacking interactions between the C60 sphere and the porphyrin moiety have been evidenced in a supramolecular complex obtained from a porphyrin-crown ether conjugate and a fullerene derivative bearing an ammonium unit.

A fullerene core to probe dendritic shielding effects

Abstract Dendrimers with a C 60 core have been obtained by cyclization of dendritic bis-malonate derivatives at the carbon sphere. The resulting bis-methanofullerene derivatives have been characterised by electrospray (ES) and/or MALDI-TOF mass spectrometries. UV–VIS absorption spectra, fluorescence spectra, and fullerene singlet excited state lifetimes have been determined in solvents of different polarity (toluene, dichloromethane, acetonitrile). These data suggest a tighter core/periphery contact upon increase of solvent polarity and dendrimer size. In all the investigated solvents, the fullerene triplet lifetimes are steadily increased with the dendrimer volume, reflecting lower diffusion rates of O 2 inside the dendrimers along the series. Measurements of quantum yields of singlet oxygen sensitization indicate that longer lived triplet states generate lower amounts of singlet oxygen ( 1 O 2 ∗ ) in dichloromethane but not in apolar toluene suggesting a tighter contact between the dendritic branches and the fullerene core in CH 2 Cl 2 . In acetonitrile, the trend in singlet oxygen production is peculiar. Effectively, enhanced singlet oxygen production is monitored for the largest dendrimer. This reflects specific interactions of excited 1 O 2 ∗ molecules with the dendritic wedges, as probed by singlet oxygen lifetime measurements, possibly as a consequence of trapping effects.

Liquid-crystalline cholesterol-based [60]fullerene hexaadducts

Two novel cholesterol-based [60]fullerene hexaadducts 1 and 2 bearing respectively 12 and 10 mesogenic cholesterol moieties were prepared following Hirschs methodology. Both hexaadducts 1 and 2 showed a smectic A phase from slightly above room temperature up to 165 °C for 1 and 180 °C for 2, whereas the malonate mesogenic promoter 5 displayed two monotropic unidentified phases at 41 °C and 67 °C and a chiral nematic phase between 67 °C and 88 °C. An increase of the mesophase stability of about 100 °C as well as a near room temperature mesomorphism was thus obtained through C60-grafting. The design consisting of the polyaddition of cholesterol moieties on the carbon truncated icosahedron used as a spherical template to create new 3D architectures, appears then to be a method of choice to obtain stable anisotropic materials and to prevent the C60 aggregation tendency. As deduced by X-ray diffraction studies, and supported by molecular modelling calculations, the two supermolecules 1 and 2 self-organize into bi-layer structures which consist of a median C60-rich slab, sandwiched between cholesteryl-containing outer layers.

A nematic [60]fullerene supermolecule: when polyaddition leads to supramolecular self-organization at room temperature

The synthesis, liquid-crystalline properties and supramolecular organization of a [60]fullerene-based supermolecule are described, and the great potential of the spherical carbonated polyhedron to produce new materials through its multiple and addressable regioselective functionalization is emphasized. Indeed, hexaaddition on the carbon sphere has allowed the preparation, in 50% yield, of the first room-temperature enantiotropic nematic C60-based material, even though the promoter was not mesomorphic. Despite the high molecular weight of such a supermolecule, the resulting material was revealed to be easily oriented in its mesophase by a magnetic field; this has allowed, by small angle X-ray diffraction investigations, a fine description of the molecular organization and of the corresponding relevant interactions involved. These results open the way to multifuntional materials that can take advantage of such an easy orientation of the grafted active chromophores (donor and acceptor) to be particularly efficient (for example in the design of photovoltaic materials).

Boron Containing Two-Photon Absorbing Chromophores. 2. Fine Tuning of the One- and Two-Photon Photophysical Properties of Pyrazabole Based Fluorescent Bioprobes

New boron containing two-photon absorbing fluorophores have been prepared. Centered on a pyrazabole central core, various conjugated systems and end groups were investigated to modulate their physicochemical properties (alkoxy, diphenylamino, and boron dipyromethene groups). One and two-photon photophysical characterizations were performed, showing efficient fluorescence in organic solvents. High two-photon absorption cross sections were determined in the 500-800 nm range. Two-photon excited microscopy images were also obtained with these new boron containing fluorescent bioprobes with laser intensities in the milliwatt range.

Self-assembly and liquid-crystalline supramolecular organizations of semifluorinated block co-dendritic supermolecules

The synthesis and self-organizing behaviour into liquid-crystalline mesophases of two libraries of segmented block co-dendrimers are described. The overall structure of the dendritic supermolecules consists of two chemically incompatible molecular moieties, covalently connected by combinatory cross-coupling reactions. One block is composed of linear perfluorinated segments (2 generations, defining the two libraries), and the bulky dendritic compartment is formed by a lipophilic poly(benzyl ether)-based dendron (3 generations). The mesomorphic properties were studied as a function of the respective generations of both blocks and of the peripheral alkyl chains’ substitution pattern. The results of these investigations reveal the formation of unusual and highly segregated supramolecular liquid-crystalline mesophases, whose arrangements are subtly controlled by the lipophilic/fluorophobic balance and dendritic connectivity.

Perfect layered arrangement of ion-paired chromophores in a crystalline non-linear optical organic salt: 2-amino-3-nitropyridinium chloride

2-Amino-3-nitropyridinium chloride is reported as a new crystalline non-linear optical organic salt, built around a two-dimensional hyperpolarisable cationic chromophore. Its crystal structure (space groupP2 1 ) reveals a quasi-perfect layered arrangement of the cations and the anions. Within each layer the chromophores are arranged in a herringbone structure and strong hydrogen bonds are present. The first hyperpolarisabilities of ion-paired chromophores calculated for 2-amino-3-nitropyridinium chloride as well as 2-amino-5-nitropyridinium chloride emphasize the favourable contribution of the inorganic anionic sublattice to the enhancement of the molecular β ijk and macroscopic χ (2) susceptibilities.

Sodium 3-methyl-4-nitrophenolate dihydrate: a crystal engineering route towards new herringbone structures for quadratic non-linear optics

Abstract Sodium 3-methyl-4-nitrophenolate dihydrate (Na3M4NP) is a new stable non-linear optical crystal of Cc monoclinic symmetry. The organic anions having an average calculated molecular hyperpolarisability β xxx ≈20×10 −30 esu are organised in a herringbone motif, inducing, together with water molecules, a very dense packing of NaO 6 edge shared octahedra. A three-dimensional network of homogeneous and short hydrogen bonds close-packs the herringbone motifs in a staggered arrangement. The crystal structure is simply described and explained in relation to basic inorganic structural models.