Emmanuel Terazzi

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.

Supramolecular Organization and Magnetic Properties of Mesogen-Hybridized Mixed-Valent Manganese Single Molecule Magnets [MnIII8MnIV4O12(Lx,y,z-CB)16(H2O)4]

Single molecule magnets (SMM) may be considered for the construction of future integrated nanodevices, provided however that some degree of ordering is imparted to these molecules (surfaces nanostructuration). Combining such nanoobjects with liquid-crystalline orderings to control their assembly and to potentially address them individually therefore appears as one promising strategy. Four mesomorphic, mixed-valent [Mn(III)(8)Mn(IV)(4)O(12)(L(x,y,z-CB))(16)(H(2)O)(4)] SMM, differing in the number of liquid-crystalline promoters, (L(x,y,z-CB)), were synthesized, and their self-organizing and magnetic properties were investigated. The influence of the peripheral modifications, and precisely how supramolecular ordering and magnetic properties may be affected by the evolution of the proto-mesogenic cyanobiphenyl-based ligands substitution pattern, was explored. Small-angle X-ray scattering studies revealed that all of the hybridized clusters self-organize into room-temperature bilayer smectic phases, mandated by the specific mesogenic functionalization and that the polymetallic cores are further organized according to a short-range pseudo-2D lattice with hexagonal and/or square symmetry. All mesomorphous hybridized dodecamanganese complexes still behave as SMM: they exhibit blocking of the magnetization at about 2.6 K as evidenced by the occurrence of frequency-dependent out-of-phase ac susceptibility signals as well as an opening of the hysteresis cycle with coercive fields varying between 0.13 and 0.6 T, depending on the surface ligands topology. Comparison of the magnetic properties within this series reveals intricate correlations between the structural features of the mesomorphous molecule magnet (i.e., symmetry of the ligands substitution patterns, molecular conformation, average intercluster distances, and respective inclination) with respect to the relative proportion of slow- and fast-relaxing species and the absolute values of the coercive fields.

Magnetic Properties of Gold Nanoparticles: A Room-Temperature Quantum Effect

Gold nanoparticles elicit a huge research activity in view of their applications in diagnostics,[1, 2] therapy,[3] drug or gene delivery,[ 4] sensing[5, 6, 7] and imaging.[8] Gold nanoparticles also display interesting catalytic[9, 10] and optical[11, 12, 13, 14] properties. This Communication focuses on the least understood and so far unused property of gold: its becoming magnetic when prepared in the form of nanoparticles. All these desirable properties, bound together in one nanometric piece of matter, possibly self-organized thanks to its ligands, make functionalized gold nanoparticles a treasurable entity for nanosciences. The ex nihilo magnetic properties of functionalized gold (and other diamagnetic metals, such a Ag or Cu) nanoparticles, that is, their ferromagnetic-like behavior, are well documented, though still poorly understood.[15] This unexpected property opens new perspectives in materials science, in particular for the design of metamaterials. One may also envisage applications in information storage and processing: nanometric magnetic particles with no obvious temperature limitation and possibly self-organizing are currently much sought-after by the computer industry and developing a room-temperature magnetic semiconductor is paramount for the realization of spintronics technologies. Herein, we wish to present the results of our own investigations into the magnetic properties of functionalized gold nanoparticles. We have made attempts at understanding this magnetic behavior using both traditional techniques (e.g. superconducting quantum interference device, SQUID, magnetometry) and other methods less common in this field, such as zerofield 197Au NMR (nuclear magnetic resonance) and SANS (smallangle neutron scattering). We also directly probed the local magnetic field at the surface of gold nanoparticles using paramagnetic TEMPO [(2,2,6,6-tetramethylpiperidin-1-yl)oxyl] radicals and ESR (electron spin resonance) spectrometry. Surprisingly, none of these experiments provided a clearer picture in fine. These “negative” results led us to pondering whether or not the explanation could be elsewhere. Our hypothesis is that the magnetism of gold (and possibly other metals) could very well originate in self-sustained persistent currents. We shall demonstrate hereafter that this hypothesis is indeed very plausible and would actually reconcile all of the experimental data reported to date.Striking results are often obtained when SQUID magnetometry is performed on functionalized Au nanoparticles, such as dodecanethiol-coated ones. Rather than being diamagnetic, as expected, the nanoparticles can be found to be para- or ferromagnetic at room temperature and above. When hysteresis is observed, the magnetization curve looks like that of a soft ferromagnet and exhibits a remnant magnetization MR and a coercive field HC, though both are rather weak. These parameters have been observed to have values that vary by orders of magnitude from sample to sample[15] (see Figure ESI-1 of the Supporting Information). Very often, the magnetization does not saturate. Diamagnetic samples are more diamagnetic than the bulk metal. Also, the magnetic observables show little dependence on temperature between 2 and 400 K. The measurements reported so far have been performed by totally independent groups, on systems that were synthesized using known chemical procedures. Figure 1 compares the magnetization of bulk gold with that of two diamagnetic samples of gold nanoparticles. It can be seen that nanoparticles have a much larger absolute diamagnetic susceptibility than massive gold. Figure 2 compares two samples of gold nanoparticles, exhibiting a paramagnetic behavior and a ferromagnetic-like one. There is a weak but clear hysteresis, and the magnetization does not really saturate even at high field values.

Dimerization of Dendrimeric Lanthanide Complexes: Thermodynamic, Thermal, and Liquid-Crystalline Properties

A series of 10 different mesomorphic semidendrimeric tridentate ligands L5-L14 grafted with terminal cyanobiphenyl groups have been synthesized. Upon reaction with Ln(NO(3))(3) (Ln = trivalent lanthanide), the central 2,6-bis(N-ethylbenzimidazol-2-yl)pyridine unit is meridionally tricoordinated to the metal to give rodlike monomeric [Ln(Lk)(NO(3))(3)] and H-shaped dimeric [Ln(2)(Lk)(2)(NO(3))(6)] complexes. For the small Lu(III) cation, the monomeric complexes are quantitatively formed in a noncoordinating CD(2)Cl(2) solution. For larger cations (Ln = Eu, Pr), the thermodynamic equilibrium 2[Ln(Lk)(NO(3))(3)] ↔ [Ln(2)(Lk)(2)(NO(3))(6)] can be evidenced across the complete ligand series. Detailed thermodynamic studies show that the dimeric complexes result from the formation of primary intermetallic nitrate bridges whose strength depends on the metallic size. For each complex, secondary nonspecific interstrand van der Waals interactions produce nonartifactual enthalpy/entropy compensation. In the absence of solvent, only the complexes with the most extended ligands L5 and L6 produce thermotropic mesophases. Layered organizations are dominant (smectic A) with the induction of nematogenic behavior at high temperature when interstrand interactions are modulated by methyl substitutions. Correlations between the trend of dimerization and the sequences of thermotropic mesophases are attempted.

Lanthanide luminescent mesomorphic complexes with macrocycles derived from diaza-18-crown-6

Four tetracatenar (L1–L4) and one hexacatenar (L5) ligands, derived from the diaza-18-crown-6 framework, are synthesized and characterized. In these ligands, the amine functions are fitted with benzoyloxybenzyl linker groups, attached either with a carbonyl function (L1) or a methylene bridge (L2–L5) and bearing alkoxy chains, R, of various lengths: R = OCH3 for L2, OC10H21 for L3 and L5, OC12H25 for L1, and OC16H33 for L4. The non-mesomorphic ligands L1 and L3–L5 react with various lanthanide salts to give complexes forming thermotropic hexagonal columnar phases, as ascertained by thermal, optical and small-angle X-ray diffraction methods. The length of the alkoxy chains (L3 and L4) does not much influence the mesogenic behaviour, irrespective of the linker function, the number of alkoxy chains, the counterion or the lanthanide ion. The best systems proved to be the nitrato lanthanide complexes with L3, which present a Colh phase over 100 °C (up to 147 °C for La) with melting transition temperatures between 58 (La) and 86 (Tb) °C. In the case of [Eu(NO3)3L3], chosen as a representative example of all the complexes in this analysis, the inter-column separation of 29.2 A agrees well with the packing of cylindrical columns resulting from an alternated stacking of the molecules, in which the two mesogenic arms extend on the same side, i.e. stacking the molecules in a bent conformation. The liquid crystalline phases containing Eu and Tb display metal-centred emission, meaning that these complexes are interesting building blocks for the design of luminescent liquid crystalline materials.

Evidence of ionic liquid crystal properties for a DODA+ salt of the keplerate [Mo132O372(CH3COO)30(H2O)72]42−

Thermal studies of a DODA+ salt of the nanoscopic hollow sphere [Mo132O372(H2O)72(CH3CO2)30]42− revealed ionic liquid crystalline properties, which were evidenced by Polarised Optical Microscopy, DSC and SA-XRD.

A Simple Chemical Tuning of the Effective Concentration: Selection of Single-, Double-, and Triple-Stranded Binuclear Lanthanide Helicates

The replacement of terminal 2-benzimidazol-6-carboxypyridine (two internal rotational degrees of freedom) with 2-benzimidazol-8-hydroxyquinoline (one internal rotational degree of freedom) into segmental bis-tridentate ligands in going from L2 and [L3-2 H](2-) to [L12 b-2 H](2-) does not significantly affect the structures of the resulting binuclear lanthanide triple-stranded helical complexes [Ln(2)(L2)(3)](6+), [Ln(2)(L3-2 H)(3)], and [Ln(2)(L12 b-2 H)(3)] (palindromic helices, intermetallic contact distance approximately 9 A, helical pitch approximately 1.4 nm per turn). However, their thermodynamic assemblies are completely different in solution, as evidenced by the spectacular decrease of the effective concentrations by two orders of magnitude for [L12 b-2 H](2-). This key parameter in the [Ln(2)(L12 b-2 H)(n)] (n=2, 3) complexes is further abruptly modulated along the lanthanide series (Ln=La to Lu), which provides an unprecedented tool for 1) tuning the number of ligand strands in the final helicates, 2) selectively coordinating lanthanides in the various complexes, and 3) controlling the ratio of lanthanide-containing polymers over discrete assemblies.

Direct proof of spontaneous translocation of lipid-covered hydrophobic nanoparticles through a phospholipid bilayer

Spontaneously translocating lipid-coated hydrophobic gold nanoparticles open doors for new biotechnology applications. Hydrophobic nanoparticles introduced into living systems may lead to increased toxicity, can activate immune cells, or can be used as nanocarriers for drug or gene delivery. It is generally accepted that small hydrophobic nanoparticles are blocked by lipid bilayers and accumulate in the bilayer core, whereas big nanoparticles can only penetrate cells through slow energy-dependent processes, such as endocytosis, lasting minutes. In contrast to expectations, we demonstrate that lipid-covered hydrophobic nanoparticles may translocate through lipid membranes by direct penetration within milliseconds. We identified the threshold size for translocation: nanoparticles with diameters smaller than 5 nm stay trapped in the bilayer, whereas those with diameters larger than 5 nm insert into the bilayer, opening pores in the bilayer. The direct proof of this size-dependent translocation was provided by an in situ observation of a single event of a nanoparticle quitting the bilayer. This was achieved with a specially designed microfluidic device combining optical fluorescence microscopy with simultaneous electrophysiological measurements. A quantitative analysis of the kinetic pathway of a single nanoparticle translocation event demonstrated that the translocation is irreversible and that the nanoparticle can translocate only once. This newly discovered one-way translocation mechanism provides numerous opportunities for biotechnological applications, ranging from targeted biomaterial elimination and/or delivery to precise and controlled trapping of nanoparticles.

Layered ionic liquid-crystalline organisations built from nano-capsules [Mo132O312S60(SO4)x(H2O)132−2x](12 + 2x)− and DODA+ cations

Two dimethyldioctadecylammonium (DODA+) salts of a new keplerate with the general formula [Mo132O312S60(SO4)x(H2O)132–2x](12 + 2x)− and abbreviated DODAn−Mo132S60 (n = 44, 56) were synthesised and characterised. Both clusters were fully characterised by the combination of Polarised Optical Microscopy, Differential Scanning Calorimetry and Small-angle X-Ray Diffraction showing self-organisation in lamellar (L) liquid crystalline phases. We demonstrated that the lamellar periodicity h of the mesophases can be controlled with the number of DODA+ associated to the clusters. Finally, these new results were compared to those gained from a previously published analogue, the fully oxo keplerate noted DODA36−Mo132 that also self-organise with temperature, but in a slightly more structured lamellar liquid crystalline phase.

Silver baits for the "miraculous draught" of amphiphilic lanthanide helicates.

The axial connection of flexible thioalkyls chains of variable length (n=1-12) within the segmental bis-tridentate 2-benzimidazole-8-hydroxyquinoline ligands [L12(Cn) -2 H](2-) provides amphiphilic receptors designed for the synthesis of neutral dinuclear lanthanides helicates. However, the stoichiometric mixing of metals and ligands in basic media only yields intricate mixtures of poorly soluble aggregates. The addition of Ag(I) in solution restores classical helicate architectures for n=3, with the quantitative formation of the discrete D(3) -symmetrical [Ln(2) Ag2(L12(C3) -2 H)(3) ](2+) complexes at millimolar concentration (Ln=La, Eu, Lu). The X-ray crystal structure supports the formation of [La(2) Ag(2) (L12(C3) -2 H)(3) ][OTf](2) , which exists in the solid state as infinite linear polymers bridged by S-Ag-S bonds. In contrast, molecular dynamics (MD) simulations in the gas phase and in solution confirm the experimental diffusion measurements, which imply the formation of discrete molecular entities in these media, in which the sulfur atoms of each lipophilic ligand are rapidly exchanged within the Ag(I) coordination sphere. Turned as a predictive tool, MD suggests that this Ag(I) templating effect is efficient only for n=1-3, while for n>3 very loose interactions occur between Ag(I) and the thioalkyl residues. The subsequent experimental demonstration that only 25 % of the total ligand speciation contributes to the formation of [Ln(2) Ag(2) (L12(C12) -2 H)(3) ](2+) in solution puts the bases for a rational approach for the design of amphiphilic helical complexes with predetermined molecular interfaces.