Effects of perfluorocarbon gases on the size and stability characteristics of phospholipid-coated microbubbles: osmotic effect versus interfacial film stabilization

Micrometer-sized bubbles coated with phospholipids are used as contrast agents for ultrasound imaging and have potential for oxygen, drug, and gene delivery and as therapeutic devices. An internal perfluorocarbon (FC) gas is generally used to stabilize them osmotically. We report here on the effects of three relatively heavy FCs, perfluorohexane (F-hexane), perfluorodiglyme (F-diglyme ), and perfluorotriglyme (F-triglyme), on the size and stability characteristics of microbubbles coated with a soft shell of dimyristoylphosphatidylcholine (DMPC) and on the surface tension and compressibility of DMPC monolayers. Monomodal populations of small bubbles (~1.3 ± 0.2 μm in radius, polydispersivity index ~8%) were prepared by sonication, followed by centrifugal fractionation. The mean microbubble size, size distribution, and stability were determined by acoustical attenuation measurements, static light scattering, and optical microscopy. The half-lives of F-hexane- and F-diglyme-stabilized bubbles (149 ± 8 and 134 ± 3 min, respectively) were about 2 times longer than with the heavier F-triglyme (76 ± 7 min) and 4-5 times longer than with air (34 ± 3 min). Remarkably, the bubbles are smaller than the minimal size values calculated assuming that the bubbles are stabilized osmotically by the insoluble FC gases. Particularly striking is that bubbles 2 orders of magnitude smaller than the calculated collapse radius can be prepared with F-triglyme, while its very low vapor pressure prohibits any osmotic effect. The interface between an aqueous DMPC dispersion and air, or air (or N(2)) saturated with the FCs, was investigated by tensiometry and by Langmuir monolayer compressions. Remarkably, after 3 h, the tensions at the interface between an aqueous DMPC dispersion (0.5 mmol L(-1)) and air were lowered from ~50 ± 1 to ~37 ± 1 mN m(-1) when F-hexane and F-diglyme were present and to ~40 ± 1 mN m(-1) for F-triglyme. Also noteworthy, the adsorption kinetics of DMPC at the interface, as obtained by dynamic tensiometry, were accelerated up to 3-fold when the FC gases were present. The compression isotherms show that all these FC gases significantly increase the surface pressure (from ~0 to ~10 mN m(-1)) at large molecular areas (70 ?(2)), implying their incorporation into the DMPC monolayer. All three FC gases increase the monolayer's collapse pressures significantly (~61 ± 2 mN m(-1)) as compared to air (~54 ± 2 mN m(-1)), providing for interfacial tensions as low as ~11 mN m(-1) (vs ~18 mN m(-1) in their absence). The FC gases increase the compressibility of the DMPC monolayer by 20-50%. These results establish that, besides their osmotic effect, FC gases contribute to bubble stabilization by decreasing the DMPC interfacial tension, hence reducing the Laplace pressure. This contribution, although significant, still does not suffice to explain the large discrepancy observed between calculated and experimental bubble half-lives. The case of F-triglyme, which has no osmotic effect, indicates that its effects on the DMPC shell (increased collapse pressure, decreased interfacial tension, and increased compressibility) contribute to bubble stabilization. F-hexane and F-diglyme provided both the smallest mean bubble sizes and the longest bubble half-lives.     

Triaryl‐1,3,5‐triazinane‐2,4,6‐triones (Isocyanurates) Peripherally Functionalized by Donor Groups: Synthesis and Study of Their Linear and Nonlinear Optical Properties

The linear optical (LO) and nonlinear optical (NLO) properties of a series of isocyanurates functionalized by donor arms at the periphery are reported herein. These octupolar derivatives were obtained in a straightforward way from commercial isocyanate derivatives and were fully characterized. Although several of these compounds are known, those that exhibited the largest NLO activities are all new compounds. In terms of second‐order activity, several of these derivatives exhibit remarkable activity/transparency tradeoffs. In terms of third‐order activity, the longer derivatives with the stronger donor groups (X=NH₂, NMe₂, or NPh₂) were shown to possess significant two‐photon absorption cross sections. These strongly luminescent derivatives exhibit two‐photon absorption cross sections up to 410 GM. DFT computations were also conducted to unravel their electronic structures and to rationalize their NLO properties. To our knowledge, the present study is the first concerned with the nonlinear optical properties of these original cyclotrimers.     

Multi-scale structuration of glasses: Observations of phase separation and nanoscale heterogeneities in glasses by Z-contrast scanning electron transmission microscopy

Chemical fluctuations are probed in glasses obtained with different thermal histories using scanning transmission electron microscopy in high angle annular dark field mode. Direct imaging of the glass structure is obtained at the sub-nanometer scale with Z-contrast. Macroscopic glass-in-glass separation is probed in a slowly quenched melt where chemical resolution allows the determination of the regions associated with Zr/Zn atoms. In a quickly cooled glass, exempt of macroscopic phase separation, a segregation of Zr/Zn atoms is still evidenced but on a different length scale, suggesting either the beginnings of glass separation or intrinsic features of the glass structure. Glass inhomogeneities must be taken into account to have a quantitative evaluation of nucleation processes. These “nano”-heterogeneities can be associated with the nucleation of zirconia phases, giving important clues to understand the nucleation pathways and the structural role of nucleating agents in aluminosilicate glasses.     

Sensitivity of multi-parametric MRI to the compressive state of the isolated intervertebral discs

Objective

Magnetic resonance imaging (MRI) offers great potential as a sensitive and noninvasive technique for describing the alterations in mechanical properties, as shown in vitro on intervertebral disc (IVD) or cartilage tissues. However, in vivo, the IVD is submitted to complex loading stimuli. Thus, the present question focuses on the influence of the mechanical loading during an MRI acquisition on the relaxation times, magnetization transfer and diffusion parameters within the IVD.

Methods

An apparatus allowing the compression of isolated IVDs was designed and manufactured in acrylonitrile butadiene styrene. IVDs were dissected from fresh young bovine tail, measured for their thickness and submitted to compression just before the MRI acquisition. Six discs received 0% (platen positioned at the initial disc thickness), 5% (platen positioned at 95% of the initial disc thickness), 10%, 20% and 40% deformation. The MRI parameters were compared between the loading states using mean and standard deviation for T1 and T2, and matrix subtraction for Magnetization Transfer, fractional anisotropy and apparent diffusion coefficient.

Results

The compression of the IVD did not lead to any significant change of the MRI parameters, except for the diffusion that decreased in the direction of the compressive stress.

Discussion

This experimental in vitro study shows that multi-parametric MRI on isolated discs in vitro is not sensitive to compression or to the partial confined relaxation that followed the compression.     

Crystal and magnetic structures and magnetic properties of selenate containing natrochalcite, A(I)M(II)2(H3O2)(SeO4)2 where A = Na or K and M = Mn, Co, or Ni

The synthesis of a series of selenate containing natrochalcite, A(I)M(II)(2)(H(3)O(2))(SeO(4))(2) where A = Na or K and M = Mn, Co, or Ni (here labeled as AMH and AMD for the hydrogenated and deuterated compounds, respectively), the X-ray crystal structure determinations from single crystals (Ni) and powder (Mn), magnetic properties, and magnetic structures of the cobalt analogues are reported. The nuclear crystal structures for NaNiH, KNiH, and KMnH are similar to those reported for the cobalt analogues (NaCoH and KCoH) and consist of chains of edge-sharing octahedra (MO(6)) which are connected by H(3)O(2) and SeO(4) to form layers which are in turn bridged by the alkali, in an octahedral coordination site, to form the 3D-framework. The magnetic properties are characterized by antiferromagnetic interaction at high temperatures and antiferromagnetic ordering at low temperatures (NaCoH, 3.5 K; KCoH, 5.9 K; KNiH, 8.5 K; and KMnH, 16 K), except for KNi(2)(H(3)O(2))(SeO(4))(2) which displays a weak ferromagnetic interaction and no long-range ordering above 2 K. The neutron magnetic structures of the cobalt analogues, studied as a function of temperature, are different for the two cobalt salts and also different from all the known magnetic structures of the natrochalcite family. Whereas the magnetic structure of NaCoD has a k = (0, 0, 0), that of KCoD has one consisting of a doubled nuclear cell, k = (0, 0, 1/2). Both compounds have four magnetic sublattices related to the four cobalt atoms of the nuclear unit cell. In NaCoD the moments are in the bc-plane, M(y) = 2.51(2) μ(B) and M(z) = 1.29(4) μ(B), with the major component along the cobalt chain and the resultant moment, 2.83(3) μ(B), making an angle of 27° with the b-axis. The sum of the moments within the cell is zero. For KCoD the moment at each cobalt site has a component along each crystallographic axis, M(x) = 2.40(3), M(y) = 1.03(3), M(z) = 1.59(8) giving a total M = 2.49(3) μ(B). Within one nuclear cell the moments are fully compensated. The moments corresponding to the cobalt atoms of the second nuclear cell comprising the magnetic unit cell are oriented in opposite directions.     

Electrochemiluminescent monomers for solid support syntheses of Ru(II)-PNA bioconjugates: multimodal biosensing tools with enhanced duplex stability

The feasibility of devising a solid support mediated approach to multimodal Ru(II)-peptide nucleic acid (PNA) oligomers is explored. Three Ru(II)-PNA-like monomers, [Ru(bpy)(2)(Cpp-L-PNA-OH)](2+) (M1), [Ru(phen)(2)(Cpp-L-PNA-OH)](2+) (M2), and [Ru(dppz)(2)(Cpp-L-PNA-OH)](2+) (M3) (bpy = 2,2'-bipyridine, phen = 1,10-phenanthroline, dppz = dipyrido[3,2-a:2',3'-c]phenazine, Cpp-L-PNA-OH = [2-(N-9-fluorenylmethoxycarbonyl)aminoethyl]-N-[6-(2-(pyridin-2yl)pyrimidine-4-carboxamido)hexanoyl]-glycine), have been synthesized as building blocks for Ru(II)-PNA oligomers and characterized by IR and (1)H NMR spectroscopy, mass spectrometry, electrochemistry and elemental analysis. As a proof of principle, M1 was incorporated on the solid phase within the PNA sequences H-g-c-a-a-t-a-a-a-a-Lys-NH(2) (PNA1) and H-P-K-K-K-R-K-V-g-c-a-a-t-a-a-a-a-lys-NH(2) (PNA4) to give PNA2 (H-g-c-a-a-t-a-a-a-a-M1-lys-NH(2)) and PNA3 (H-P-K-K-K-R-K-V-g-c-a-a-t-a-a-a-a-M1-lys-NH(2)), respectively. The two Ru(II)-PNA oligomers, PNA2 and PNA3, displayed a metal to ligand charge transfer (MLCT) transition band centered around 445 nm and an emission maximum at about 680 nm following 450 nm excitation in aqueous solutions (10 mM PBS, pH 7.4). The absorption and emission response of the duplexes formed with the cDNA strand (DNA: 5'-T-T-T-T-T-T-T-A-T-T-G-C-T-T-T-3') showed no major variations, suggesting that the electronic properties of the Ru(II) complexes are largely unaffected by hybridization. The thermal stability of the PNA·DNA duplexes, as evaluated from UV melting experiments, is enhanced compared to the corresponding nonmetalated duplexes. The melting temperature (T(m)) was almost 8 °C higher for PNA2·DNA duplex, and 4 °C for PNA3·DNA duplex, with the stabilization attributed to the electrostatic interaction between the cationic residues (Ru(II) unit and positively charged lysine/arginine) and the polyanionic DNA backbone. In presence of tripropylamine (TPA) as co-reactant, PNA2, PNA3, PNA2·DNA and PNA3·DNA displayed strong electrochemiluminescence (ECL) signals even at submicromolar concentrations. Importantly, the combination of spectrochemical, thermal and ECL properties possessed by the Ru(II)-PNA sequences offer an elegant approach for the design of highly sensitive multimodal biosensing tools.     

Mixed metallic Ba(Co,Fe)X(0.2)O(3-δ) (X = F, Cl) hexagonal perovskites: drastic effect of Fe-incorporation on structural and electronic features

Starting from the parent 10H-Ba(5)Co(5)X(1-x)O(13-δ) (trimeric strings of face-sharing CoO(6) octahedra with terminal CoO(4) tetrahedra, stacking sequence (chhch')(2)) and 6H-Ba(6)Co(6)X(1-x)O(16-δ) (similar with tetrameric strings, stacking sequence chhhch') hexagonal perovskites forms (X = F, Cl; c, h = [BaO(3)] layers ; h' = [BaOX(1-y)] layers), we show here that the Fe incorporation leads to large domains of solid solutions for both X = F and Cl but exclusively stabilizes the 10H-form independently of the synthesis method. In this form, the lowest concentration of h-layers is stabilized by a sensitive metal reduction with increasing the Fe ratio. In a more general context of competition between several hexagonal perovskite polymorphs available for most of the transition metals, this redox change is most probably the key factor driving 1D (face-sharing chains) to 3D (corner-sharing) connectivities. Strikingly, ND data evidence the location of oxygen deficiencies in the tetrahedral (Co/Fe) coordination. This effect is exaggerated at high temperature, while (Co/Fe)O(4-δ) coordinations are completed by the displacement of X(-) anions toward the (Co/Fe) sphere of coordination following a "push-and-pull" mechanism within h'-[BaOX(1-y)] layers. The Fe-incorporation is also accompanied by increasing conduction gaps with predominant 1D variable range hopping. The full series show antiferromagnetic behavior with increasing T(N) as [Fe] increases. For Fe-rich compounds T(N) is estimated about 600 K, as rarely observed for hexagonal perovskite compounds. Finally, magnetic structures of all iron-doped compounds show a site-to-site AFM ordering, different of the magnetic structure of Co-only parent compounds. Here, DFT calculations predict low-spin octahedral Co configurations, but high-spin Fe species in the same sites.     

Bi(OTf)3-catalyzed cycloisomerization of aryl-allenes

Intramolecular hydroarylation of allenes was achieved under very mild conditions using bismuth(III) triflate as the catalyst. Efficient functionalization of activated and nonactivated aromatic nuclei led to C-C bond formation through a formal Ar-H activation. A tandem bis-hydroarylation of the allene moiety was also developed giving access to various interesting polycyclic structures.     

Enzyme-free detection and quantification of double-stranded nucleic acids

We have developed a fully enzyme-free SERRS hybridization assay for specific detection of double-stranded DNA sequences. Although all DNA detection methods ranging from PCR to high-throughput sequencing rely on enzymes, this method is unique for being totally non-enzymatic. The efficiency of enzymatic processes is affected by alterations, modifications, and/or quality of DNA. For instance, a limitation of most DNA polymerases is their inability to process DNA damaged by blocking lesions. As a result, enzymatic amplification and sequencing of degraded DNA often fail. In this study we succeeded in detecting and quantifying, within a mixture, relative amounts of closely related double-stranded DNA sequences from Rupicapra rupicapra (chamois) and Capra hircus (goat). The non-enzymatic SERRS assay presented here is the corner stone of a promising approach to overcome the failure of DNA polymerase when DNA is too degraded or when the concentration of polymerase inhibitors is too high. It is the first time double-stranded DNA has been detected with a truly non-enzymatic SERRS-based method. This non-enzymatic, inexpensive, rapid assay is therefore a breakthrough in nucleic acid detection.     

Stacking of Self‐Assembled Surface Micelles in Ultrathin Films

Nonpolar fluorophilic/lipophilic tetrablock amphiphiles are investigated on the surface of water and on solid substrates using compression isotherms, Brewster angle microscopy, and atomic force microscopy. At low pressures, the tetrablocks form monolayers of closely packed surface hemimicelles. Further compression causes a 2D/3D transition. At the end of the plateau, half of the deposited material is expelled forming a second monolayer on top of the initially formed monolayer. Both layers of the films consist of surface micelles, thus providing the first example of spontaneous or compression‐driven stacking of self‐assembled nano‐objects.