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

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.

A quantitative assessment of chemical perturbations in thermotropic cyanobiphenyls.

Chemical programming of the temperature domains of existence of liquid crystals is greatly desired by both academic workers and industrial partners. This contribution proposes to combine empirical approaches, which rely on systematic chemical substitutions of mesogenic molecules followed by thermal characterizations, with a rational thermodynamic assessment of the effects induced by chemical perturbations. Taking into account the similarities which exist between temperature-dependent cohesive Gibbs free energy densities (CFEDs) and pressure-temperature phase diagrams modeled with the Clapeyron equation, chemical perturbations are considered as pressure increments along phase boundaries, which control the thermotropic liquid crystalline properties. Taking the familiar calamitic amphiphilic cyanobiphenyl-type mesogens as models, the consequences of (i) methyl substitution of the aromatic polar heads and (ii) connections of bulky silyl groups at the termini of the apolar flexible alkyl chain on the melting and clearing temperatures are quantitatively analyzed. Particular efforts were focused on the translation of the thermodynamic rationalization into a predictive tool accessible to synthetic chemists mainly interested in designing liquid crystals with specific technological applications.

Chemical Programming of the Domain of Existence of Liquid Crystals.

This work illustrates how enthalpy and entropy changes responsible for successive phase transitions of cyanobiphenyl-based liquid crystals can be combined to give cohesive free energy densities. These new parameters are able to rationalize and quantify the demixing of the melting and clearing processes that occur in thermotropic liquid crystals. Minor structural variations at the molecular level can be understood as pressure increments that alter either the melting or clearing temperatures in a predictable way. This assessment of microsegregation operating in amphiphilic molecules paves the way for the chemical programming of the domain of existence of liquid-crystalline phases.

Synthesis, characterization, and tuning of the liquid crystal properties of ionic materials based on the cyclic polyoxothiometalate [{Mo4O4S4(H2O)3(OH)2}2(P8W48O184)](36-).

A series of compounds resulting from the ionic association of a nanoscopic inorganic cluster of formula [K2NaxLiy{Mo4O4S4(OH)2(H2O)3}2(HzP8W48O184)]((34-x-y-z)-), 1, with several organic cations such as dimethyldioctadecylammonium DODA(+), trimethylhexadecylammonium TMAC16(+), alkylmethylimidazoliums mimCn(+) (n = 12-20) and alkyl-dimethylimidazoliums dmimCn(+) (n = 12 and 16) was prepared and characterized in the solid state by FT-IR, EDX, Elemental analysis, TGA and solid state NMR. The solid state NMR experiments performed on (1)H, (13)C and (31)P nuclei evidenced the interactions between the cations and 1 as well as the organization of the alkyl chains of the cations within the solid. Polarized optical microscopy, DSC and SA-XRD experiments implicated mesomorphic phases for DODA(+) and mimCn(+) salts of 1. The crystallographic parameters were determined and demonstrated that the inter-lamellar spacing could be controlled upon changing the length of the alkyl chain, a very interesting result if we consider the huge size of the inorganic cluster 1 and the simple nature of the cations.

Tracking "apolar" NMe4+ ions within two polyoxothiomolybdates that have the same pores: smaller clathrate and larger highly porous clusters in action.

Two nanosized polyoxothiometalates were synthesized based on linking oxomolybdate building blocks with {Mo2O2S2}(2+) groups. Remarkably, both compounds are formed selectively primarily upon changing the related concentrations in a logical way; they exhibit common structural features based on the same {Mo9O6S3}-type pores, which result in connections between {Mo6O21} pentagons and {Mo2O2S2}(2+) linkers. Whereas the much larger spherical Mo132-type Keplerate contains twenty pores, the smaller Mo63 -type cluster remarkably contains only two. The two compounds and a similar Keplerate exhibit interesting supramolecular properties related to interactions with the unusual predominantly apolar NMe4(+) cations. Structural characterization of the Mo63 -type compound reveals in the solid state a clathrate-like species that contains four NMe4(+) cations embedded in two types of structurally well-adapted pockets. Related NMR spectroscopic investigations in solution using NMe4(+) as the NMR spectroscopic probe are in agreement with the solid-state description. (1)H NMR spectroscopic experiments (1D variable-temperature, 2D total correlation spectroscopy (TOCSY), exchange spectroscopy (EXSY), and diffusion-ordered spectroscopy (DOSY)) feature firmly immobilized and mobile NMe4(+) ions in relationship with the type of host-guest arrangements. The use of the (1)H NMR DOSY spectroscopic methodology has been successfully applied to track the interactions of the NMe4(+) cations with the {Mo9O6S3} pores of a sulfurated Keplerate, thereby allowing the first quantitative analysis of this type of plugging process. The stability constant K=(210±20) mol(-1) L is discussed related to the character of the process.

Enthalpy-entropy compensation combined with cohesive free-energy densities for tuning the melting temperatures of cyanobiphenyl derivatives.

This work illustrates how minor structural perturbations produced by methylation of 4'-(dodecyloxy)-4-cyanobiphenyl leads to enthalpy-entropy compensation for their melting processes, a trend which can be analyzed within the frame of a simple intermolecular cohesive model. The transformation of the melting thermodynamic parameters collected at variable temperatures into cohesive free-energy densities expressed at a common reference temperature results in a novel linear correlation, from which melting temperatures can be simply predicted from molecular volumes.

Supramolecular organization and magnetic properties of mesogen-hybridized mixed-valent manganese single molecule magnets [Mn(III)8Mn(IV)4O12(L(x,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.

Protonation and complexation properties of polyaromatic terdentate six-membered chelate ligands.

The successive protonation steps occurring in 2,2';6',2″-terpyridine (L1) are characterized by a strong affinity for the first entering proton (ΔG(connect)(H,L1) = −17 kJ/mol) followed by allosteric anticooperativity (ΔE(interaction)(H,H,L1) = 6 kJ/mol), a behavior mirrored by 2,6-bis(azaindolyl)pyridine (L2) despite the extension of the chelate ring size from five members (L1) to six members (L2; ΔG(connect)(H,L2) = −28 kJ/mol and ΔE(interaction)(H,H,L2) = 7 kJ/mol). On the contrary, 2,6-bis(8-quinolinyl)pyridine (L3) is less eager for the initial protonation (ΔG(connect)(H,L3) = −10 kJ/mol), but the fixation of a second proton in [H2L3]2+ is driven to completion by positive cooperativity (ΔE(interaction)(H,H,L3) = −5 kJ/mol). Because of its unusual ability to adopt a cis­cis conformation with a large affinity for the entering protons, L2 has been selected for exploring the reactivity of a terdentate fused six-membered chelate with labile metallic cations possessing increasing electrostatic factors along the series Mz+ = Li+ < Mg2+ ≈ Zn2+ < Y3+. Spectroscopic, thermodynamic, and structural studies demonstrate that covalency is crucial for stabilizing the complexes [Zn(L2)n]2+. With the highly charged Y3+ cation, hydrolysis drastically competes with ligand complexation, but anhydrous conditions restore sufficient selectivity for the successful coordination of neutral fused six-membered polyaromatic terdentate chelates with large 4f-block cations.

Magnetism in gold nanoparticles.

Gold nanoparticles currently elicit an intense and very broad research activity because of their peculiar properties. Be it in catalysis, optics, electronics, sensing or theranostics, new applications are found daily for these materials. Approximately a decade ago a report was published with magnetometry data showing that gold nanoparticles, most surprisingly, could also be magnetic, with features that the usual rules of magnetism were unable to explain. Many ensuing experimental papers confirmed this observation, although the reported magnetic behaviours showed a great variability, for unclear reasons. In this review, most of the experimental facts pertaining to "magnetic gold" are summarized. The various theories put forth for explaining this unexpected magnetism are presented and discussed. We show that despite much effort, a satisfying explanation is still lacking and that the field of hypotheses should perhaps be widened.

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.

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.

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.

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.

The Quest for Nanoscale Magnets: The example of [Mn12] Single Molecule Magnets.

Recent advances on the organization and characterization of [Mn12] single molecule magnets (SMMs) on a surface or in 3D are reviewed. By using nonconventional techniques such as X-ray magnetic circular dichroism (XMCD) and scanning tunneling microscopy (STM), it is shown that [Mn12]-based SMMs deposited on a surface lose their SMM behavior, even though the molecules seem to be structurally undamaged. A new approach is reported to get high-density information-storage devices, based on the 3D assembling of SMMs in a liquid crystalline phase. The 3D nanostructure exhibits the anisotropic character of the SMMs, thus opening the way to address micrometric volumes by two photon absorption using the pump-probe technique. We present recent developments such as µ-SQUID, magneto-optical Kerr effect (MOKE), or magneto-optical circular dichroism (MOCD), which enable the characterization of SMM nanostructures with exceptional sensitivity. Further, the spin-polarized version of the STM under ultrahigh vacuum is shown to be the key tool for addressing not only single molecule magnets, but also magnetic nano-objects.

Thermodynamics of dimerization in solution as a rational tool for inducing nematic vs. smectic organizations in lanthanidomesogens.

The judicious tuning of simple thermodynamic parameters controlling dimerization processes in solution induces a rational switch between smectic and nematic organizations in thermotropic lanthanide-containing liquid crystals.

Host-guest adaptability within oxothiomolybdenum wheels: structures, studies in solution and DFT calculations.

The formation of host-guest cyclic architectures, built up through the self-condensation process of [Mo(2)O(2)S(2)](2+) oxothiocations around linear dicarboxylate ions such as adipate (Adip(2-)), suberate (Sub(2-)) and azelaate (Azel(2-)) anions is reported. The complexes [Mo(12)Adip](2-), [Mo(12)Sub](2-) and [Mo(14)Azel](2-) have been characterized in the solid state by X-ray diffraction and in solution by (1)H NMR in different solvents (D(2)O, DMF, DMSO and CD(3)CN). The host-guest dynamics appear to be dependent on the nature of the system and are mainly governed by mutual adaptability between the host and the guest. (1)H NMR DOSY experiments show systematic differences, either positive or negative between the experimental and calculated molecular weights which appear to be correlated with the charge of the anion. The relative stabilities of the twelve-membered rings containing the Adip(2-), Pim(2-) (pimelate) or Sub(2-) anions were determined experimentally and decrease according to the order [Mo(12)Adip](2-) > [Mo(12)Pim](2-) > [Mo(12)Sub](2-). The host-guest adaptability depends on the length of the carbon chain and gives rise to selective encapsulation processes. Finally, theoretical DFT investigations in the gas phase yielded conformations whose symmetry and geometrical parameters proved consistent with X-ray structures and (1)H NMR spectra recorded in DMSO or DMF. Energy calculation highlights the high flexibility of the ring showing that only 3.1 kJ mol(-1) accompanies the conformational change from circular to elliptical. The host-guest bond energy (Delta E) calculated for the Mo(12)-based clusters is consistent with the experimental stability scale, major variations being due to some constraints undergone by the central alkyl chain.

Structure, formation, and dynamics of Mo(12) and Mo(16) oxothiomolybdenum rings containing terephtalate derivatives.

The influence of rigid or semirigid dicarboxylate anions, terephtalate (TerP(2-)), isophtalate (IsoP(2-)), and phenylenediacetate (PDA(2-)) on the self-condensation process of the [Mo(2)O(2)S(2)](2+) dioxothio cation has been investigated. Three new molybdenum rings, [Mo(12)O(12)S(12)(OH)(12)(TerP)](2-) ([Mo(12)TerP](2-)), [Mo(16)O(16)S(16)(OH)(16)(H(2)O)(4)(PDA)(2)](4-) ([Mo(16)(PDA)(2)](4-)), and [Mo(16)O(16)S(16)(OH)(16)(H(2)O)(2)(IsoP)(2)](4-) ([Mo(16)(IsoP)(2)](4-)) have been isolated and unambiguously characterized in the solid state by single-crystal X-ray studies and in solution by various NMR methods and especially by diffusion-correlated NMR ((1)H DOSY) spectroscopy, which was shown to be a powerful tool for the characterization and speciation of templated molybdenum ring systems in solution. Characterization by FT-IR and elemental analysis are also reported. The dynamic and thermodynamic properties of both the sixteen-membered rings were studied in aqueous medium. Specific and distinct behaviors were revealed for each system. The IsoP(2-)/[Mo(2)O(2)S(2)](2+) system gave rise to equilibrium, involving mono-templated [Mo(12)IsoP](2-) and bis-templated [Mo(16)(IsoP)(2)](4-) ions. Thermodynamic parameters have been determined and showed that the driving-force for the formation of the [Mo(16)(IsoP)(2)](4-) is entropically governed. However, whatever the conditions (temperature, proportion of reactants), the PDA(2-)/[Mo(2)O(2)S(2)](2+) system led only to a single compound, the [Mo(16)(PDA)(2)](4-) ion. The latter exhibits dynamic behavior, consistent with the gliding of both the stacked aromatic groups. Stability and dynamics of both Mo(16) rings was related to weak hydrophobic or pi-pi stacking inter-template interactions and inner hydrogen-bond network occurring within the [Mo(16)(IsoP)(2)](4-) and [Mo(16)(PDA)(2)](4-) ions.