Jelena Jeftić

Light-induced phase separation in the [Fe(ptz)6] (BF4)2 spin-crossover single crystal

We present novel insight on like-spin domains (LSD) in cooperative spin transition solids by following the photo-transformation and the subsequent relaxation of a [ Fe(ptz)6] (BF4)2 single crystal in the vicinity of the light-induced instability. Self-organization under light is observed, accompanied by Barkhausen-like noise and jumps which reveal the presence of elastic interactions between LSDs. The light-induced phase separation process is discussed in terms of a dynamic potential providing spinodal instability in the corresponding temperature range. This useful concept is applicable to all types of switchable molecular solids.

Effects of a novel archaeal tetraether-based colipid on the in vivo gene transfer activity of two cationic amphiphiles.

Gene therapy for treating inherited diseases like cystic fibrosis might be achieved using multimodular nonviral lipid-based systems. To date, most optimizations have concerned cationic lipids rather than colipids. In this study, an original archaeal tetraether derivative was used as a colipid in combination with one or the other of two monocationic amphiphiles. The liposomes obtained, termed archaeosomes, were characterized regarding lipid self-assembling properties, macroscopic/microscopic structures, DNA condensation/neutralization/relaxation abilities, and colloidal stability in the presence of serum. In addition, gene transfer experiments were conducted in mice with lipid/DNA complexes being administered via systemic or local delivery routes. Altogether, the results showed that the tetraether colipid can provide complexes with different in vivo transfection abilities depending on the lipid combination, the lipid/colipid molar ratio, and the administration route. This original colipid appears thus as an innovative modular platform endowed with properties possibly beneficial for fine-tuning of in vivo lipofection and other biomedical applications.

Applications of Extremophilic Archaeal Lipids in the Field of Nanocarriers for Oral/Topical Drug Delivery

Extreme environments are mainly occupied by Archaea that contain in their cytoplasmic membrane unique mono- and bi-polar ether lipids that exhibit extraordinary resistance towards chemical and/or enzymatic degradation, over a wide range of pH values, extreme temperatures, and high salt concentrations. The archaeal core lipid structures show considerable variation within the various subgroups of the Archaea, but there are groupings of structural types that can be associated with the three principal archaeal phenotypes. These unusual lipids play a key role in the adaptation of the halophilic, methanogenic, (hyper)thermophilic/thermoacidophilic Archaea to extreme habitats by optimizing membrane composition and properties in direct response to the growth conditions of the organisms. The uniqueness of archaeal lipid structures and functions within membranes has prompted a great deal of interest in the use of natural lipids or synthetic analogues as innovative materials for the development of biotechnological applications. In this review, recent uses of diether-type and tetraether-type lipids as nanocarriers in the drug delivery field are discussed, with special attention to the promising oral/topical administration routes.

Supramolecular structures based on new bolaamphiphile molecules investigated by small angle and wide angle X-ray scattering and polarized optical microscopy.

In this paper, we present a study of the structural and self-assembling properties of a new family of bolaamphiphiles. These bolaamphiphiles are unsymmetrical, having one sugar polar head at one side and one glycine betaine polar head at the other side. The variations that we introduced concern the length of the main bridging chain that connects the two polar heads as well as the length of the side chain linked at the anomeric position of the sugar moiety. Another variation concerns the introduction of a diacetylenic unit into the main chain in order to rigidify it. We have performed small angle X-ray scattering (SAXS) and wide angle X-ray scattering (WAXS) on the dry compounds as a function of temperature and observed the lamellar structures. We also measured the SAXS and WAXS spectra of aqueous solutions of these compounds that have shown various lamellar structures. The hydrocarbon chain fluidity and, as a consequence, the interlamellar distance varied as a function of temperature. The obtained SAXS and WAXS results are compared with the polarized optical microscopy measurements.

Efficient transfection of Xenobiotic Responsive Element-biosensor plasmid using diether lipid and phosphatidylcholine liposomes in differentiated HepaRG cells

In this study, we evaluated cationic liposomes prepared from diether-NH2 and egg phosphatidylcholine (EPC) for in vitro gene delivery. The impact of the lipid composition, i.e. the EPC and Diether-NH2 molar ratio, on in vitro transfection efficiency and cytotoxicity was investigated using the human HEK293T and hepatoma HepaRG cells known to be permissive and poorly permissive cells for liposome-mediated gene transfer, respectively. Here, we report that EPC/Diether-NH2-based liposomes enabled a very efficient transfection with low cytotoxicity compared to commercial transfection reagents in both HEK293T and proliferating progenitor HepaRG cells. Taking advantage of these non-toxic EPC/Diether-NH2-based liposomes, we developed a method to efficiently transfect differentiated hepatocyte-like HepaRG cells and a biosensor plasmid containing a Xenobiotic Responsive Element and a minimal promoter driving the transcription of the luciferase reporter gene. We demonstrated that the luciferase activity was induced by a canonical inducer of cytochrome P450 genes, the benzo[a]pyrene, and two environmental contaminants, the fluoranthene, a polycyclic aromatic hydrocarbon, and the endosulfan, an organochlorine insecticide, known to induce toxicity and genotoxicity in differentiated HepaRG cells. In conclusion, we established a new efficient lipofection-mediated gene transfer in hepatocyte-like HepaRG cells opening new perspectives in drug evaluation relying on xenobiotic inducible biosensor plasmids.

Small-Angle and Wide-Angle X-Ray Scattering Study of Slow Relaxation Following Phase Transitions of New Bolaamphiphiles Based on N-(12-Betainylamino-Dodecane)-octyl β-D-Glucofuranosiduronamide Chloride.

ABSTRACT In the present study, we investigated the polymorphism and its time-dependence of a new series of bolaamphiphile molecules based on N-(12-Betainylamino-dodecane)-octyl β-D-Glucofuranosiduronamide Chloride. To obtain six members of this series, the length of the main bridging chain and the lateral chain were varied in order to modify the hydrophilic–lipophilic balance. Another chemical modification was to introduce a diacetylenic unit in the middle of the bridging chain to study the influence of the π–π stacking on the supramolecular organization of these molecules. Dry bolaamphiphiles self-organize in supramolecular structures such as lamellar crystalline structure, Lc; lamellar gel structure, Lβ′; lamellar fluid structure, Lα; and lamellar isotropic structure, L. Thermal hysteresis of these structures, following phase transitions, are investigated by small-angle and wide-angle X-ray scattering. Once the thermal cycle is accomplished, the system remains in the kinetically stabilized undercooled high-temperature phase at the temperature of 20°C. Subsequently, the time-dependence of the relaxation to the thermodynamically stable phase is followed, and very slow relaxation for a period on the order of hours or days is observed. The study of the polymorphism and the stability of various phases of this new series of bolaamphiphiles—which are issued from natural primary resources (sugar beet and wheat) and thus interesting for potential application in pharmaceutical, cosmetics, or food industry—was undertaken in this work.

Internal pressure in a molecular crystal under influence of light: the interplay with the structural phase transition

The molecular crystal [Fe(ptz)6](BF4)2, where ptz is 1-n-propyltetrazole, is a member of family of spin transition complexes. It shows a thermal spin transition from the highest spin multiplicity state (high-spin, S = 2) to the lowest multiplicity state (low-spin, S = 0). The spin transition is a matter of ligand field strength for this iron(II) complex, where iron is surrounded by nitrogen atoms. Owing to the important difference in radii between metal and ligand in the two aforementioned states of complex, one observes a difference of ∼5% in crystal volume. It follows that the spin transition may be accompanied by the crystallographic phase transition as well. At low temperatures, one can induce the spin transition of the complex by irradiating the crystal with the blue laser light. On the other hand, upon cooling, the high-spin state can be stabilised by red light. Recently, we obtained a spin density map of the photoexcited crystal, where the major part of spin distribution is situated around iron atoms. This information gives us an important structural parameter in the photoexcited metastable high-spin state of an iron-propyltetrazole single crystal.

Lipid bolaamphiphiles for fabricating membrane-mimetic biomaterials

Abstract In this chapter, we give an overview of the state of art concerning biomimetic membranes based on bolaamphiphiles. After the general introduction of the chapter, we describe the classification between natural and synthetic bolaamphiphiles. The main part of the chapter is subdivided into six parts each presenting the actual state of art in relation to bolaamphiphile biomimetic membranes. In particular, we present translocation across vesicle membranes, membrane dynamics, flip-flop, self-assembly of bolaamphiphiles, nanostructures based on bolaamphiphiles, structural analysis and experimental techniques for characterizing bolaamphiphiles, synthesis of some original bolaamphiphiles, and finally applications such as recognition, encapsulation, drug delivery, and gene delivery.

Structural and rheological properties of kappa (κ)-carrageenans covalently modified with cationic moieties

Cationized kappa-carrageenans containing 2-hydroxy-3-(trimethylammonium)propyl groups with various degrees of substitution (0.13–0.75) were synthesized by reaction of sulfated polysaccharides with 3-chloro-2-hydroxypropyltrimethyl ammonium chloride (QUAB 188) in alkaline solutions through the generation of the corresponding 2,3-epoxy reagent in situ. The structure of the modified algal polysaccharides was characterized without any further treatment or after methanolysis and/or enzymatic depolymerization, by means of spectroscopic tools (FT-IR, NMR, Mass spectrometry) and high-performance size exclusion chromatography (HPSEC). Significant differences in the rheological properties of these cationized kappa-carrageenans have been found depending on the DS values and the presence of KCl salt. Despite their lower molecular weights in comparison with native polysaccharides, cationized kappa-carrageenans with a DS of 0.75 exhibited high viscosity and gelling behaviors mediated by the high density of quaternary ammonium groups.

Spectroscopic Investigations of Fine‐Tuned Energy Differences in a Series of Substituted Rhenium and Technetium Complexes [M(RPhCS3)2(RPhCS2)] {M=Re, 99Tc; R=H, F, Me, Et, OMe}

Abstract A series of compounds of interest for nuclear medicine, [M(RPhCS3)2(RPhCS2)] (M=Re or 99Tc, R=H, F, Me, Et, OMe), was investigated by spectroscopic analysis. We compared the relative increase in energy shift of the absorption bands of the same assignation. The highest energy is observed in case of meta‐ or ortho‐substituted complexes compared with the lowest one in the case of para‐substituted compounds, which we discuss in terms of steric influences. The energy shift, related to the ligand field strength, and further to the Lewis basicity gives us a spectrochemical series for variously substituted phenyl rings of the ligands, both in the rhenium and technetium series of complexes (→shows the increasing ligand field).