Synthesis and cytotoxic evaluation of cis-locked and constrained analogues of combretastatin and combretastatin A4

A series of cis-locked stilbenic compounds related to combretastatin and combretastatin A4 has been designed and synthesized. The cytotoxic effects of these rigid analogues were evaluated as well as their abilities to inhibit tubulin polymerization.     

A metal-directed self-assembled electroactive cage with bis(pyrrolo)tetrathiafulvalene (BPTTF) side walls

A straightforward synthesis of a bis(pyrrolo)tetrathiafulvalene (BPTTF)-based tetratopic ligand bearing four pyridyl units is described. The first example of a TTF-based self-assembled cage has been produced from this redox-active ligand through metal-directed synthesis with a cis-coordinated square-planar Pt(II) complex. The resulting cage corresponds to a trigonal-prismatic structure, as shown by X-ray crystallography. A UV-vis titration indicated that the electron-rich cavity can be used to incorporate one molecule of tetrafluorotetracyano-p-quinodimethane (TCNQF(4)).     

Synthesis and electronic properties of D-A-D triads based on 3-alkoxy-4-cyanothiophene and benzothienothiophene blocks

3-Alkoxy-4-cyanothiophene units are used as building block for the synthesis of conjugated donor-acceptor-donor (D-A-D) triads. The donor part consists of benzothienothiophene end groups associated with the alkoxy groups of the 3-alkoxy-4-cyanothiophene, while the central acceptor part is formed by combining the electron-withdrawing cyano group with thiophene or benzothiadiazole units.     

Synthesis and electronic properties of terthienyls β-substituted by (thienyl)cyanovinylene groups

Terthienyls functionalized at their two outer β,β′-positions by 2- and 3-(thienyl)cyanovinyl groups have been synthesized by basic condensation. The analysis of their electronic properties by UV-vis spectroscopy and cyclic voltammetry shows that the mode of derivatization affects essentially the LUMO level of the conjugated system.     

Metalla-Assembled Electron-Rich Tweezers: Redox-Controlled Guest Release Through Supramolecular Dimerization

Developing methodologies for on-demand control of the release of a molecular guest requires the rational design of stimuli-responsive hosts with functional cavities. While a substantial number of responsive metallacages have already been described, the case of coordination-tweezers has been less explored. Herein, we report the first example of a redox-triggered guest release from a metalla-assembled tweezer. This tweezer incorporates two redox-active panels constructed from the electron-rich 9-(1,3-dithiol-2-ylidene)fluorene unit that are facing each other. It dimerizes spontaneously in solution and the resulting interpenetrated supramolecular structure can dissociate in the presence of an electron-poor planar unit, forming a 1:1 host–guest complex. This complex dissociates upon tweezer oxidation/dimerization, offering an original redox-triggered molecular delivery pathway.     

Self‐assembly of N‐carboxyethylchitosan near the isoelectric point

For the first time the possibility to obtain nanostructures by self‐assembly of chitosan polyampholytic derivative was demonstrated. The self‐assembly of N‐carboxyethylchitosan (CECh) took place only near its isoelectric point (pH 5.0–5.6). Out of the pH range 5.0–5.6, CECh aqueous solutions behaved as real solutions. Dynamic light scattering and atomic force microscopy analyses revealed that spherically shaped or rod/worm‐like nanosized assemblies were formed depending on the polymer molar mass, pH value, and polymer concentration. CECh of two different molar masses was studied in concentrations ranging from 0.01 to 0.1 mg/mL. The structures from CECh of weight‐average molar mass (M_w ) 4.5 × 10³ g/mol were spherical regardless the pH and polymer concentration. In contrast, CECh of high molar mass (HMMCECh, M_w = 6.7 × 10⁵ g/mol) formed self‐assemblies with spherical shape only at pH 5.0 and 5.6. At pH 5.2 spherical nanoparticles were obtained only at polymer concentration 0.01 mg/mL. The mean hydrodynamic diameter (D_h) of the obtained nanoparticles was in the range from 30 to 980 nm. On increasing the concentration, aggregation of the nanoparticles appeared, and at HMMCECh concentration 0.1 mg/mL, rod/worm‐like structures were obtained. © 2008 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 46: 6712–6721, 2008     

AFM investigation of Pseudomonas aeruginosa lectin LecA (PA-IL) filaments induced by multivalent glycoclusters

Atomic force microscopy reveals that Pseudomonas aeruginosa LecA (PA-IL) and a tetra-galactosylated 1,3-alternate calix[4]arene-based glycocluster self-assemble according to an aggregative chelate binding mode to create monodimensional filaments. Lectin oligomers are identified along the filaments and defects in chelate binding generate branches and bifurcations. A molecular model with alternate 90° orientation of LecA tetramers is proposed to describe the organisation of lectins and glycoclusters in the filaments.     

Polarizable interaction potential for molecular dynamics simulations of actinoids(III) in liquid water

In this work, we have developed a polarizable classical interaction potential to study actinoids(III) in liquid water. This potential has the same analytical form as was recently used for lanthanoid(III) hydration [M. Duvail, P. Vitorge, and R. Spezia, J. Chem. Phys. 130, 104501 (2009)]. The hydration structure obtained with this potential is in good agreement with the experimentally measured ion-water distances and coordination numbers for the first half of the actinoid series. In particular, the almost linearly decreasing water-ion distance found experimentally is replicated within the calculations, in agreement with the actinoid contraction behavior. We also studied the hydration of the last part of the series, for which no structural experimental data are available, which allows us to provide some predictive insights on these ions. In particular we found that the ion-water distance decreases almost linearly across the series with a smooth decrease of coordination number from nine to eight at the end.     

Asymmetric catalytic oxidative cleavage of polycyclic systems: the synthesis of atropisomeric diazonanes and diazecanes

Oxidative cleavage of internal double bonds in polycyclic systems can give access to compounds containing medium- to large-sized rings. In this example, the nine- and ten-membered ring containing compounds that resulted from the mCPBA-mediated (mCPBA=meta-chloroperoxybenzoic acid) oxidative cleavage reaction were shown to exhibit atropisomerism. The reaction of the polycyclic system with catalytic amounts of ruthenium tetraoxide followed by diol cleavage achieved the same synthetic goal. Use of the Nishiyama-Beller ruthenium-based catalysts enabled the synthesis of optically-enriched samples, providing the first example of an atropselective oxidative cleavage reaction.     

A “Multi-Heavy-Atom” Approach toward Biphotonic Photosensitizers with Improved Singlet-Oxygen Generation Properties

Two trispicolinate 1,4,7-triazacyclonane (TACN)-based ligands bearing three picolinate biphotonic antennae were synthetized and their Yb³⁺ and Gd³⁺ complexes isolated. One series differs from the other by the absence ( L¹ )/presence ( L² ) of bromine atoms on the antenna backbone, offering respectively improved optical and singlet-oxygen generation properties. Photophysical properties of the ligands, complexes and micellar Pluronic suspensions were investigated. Complexes exhibit high two-photon absorption cross-section combined either with NIR emission (Yb) or excellent ¹O₂ generation (Gd). The very large intersystem crossing efficiency induced by the combination of bromine atom and heavy rare-earth element was corroborated with theoretical calculations. The ¹O₂ generation properties of L² Gd micellar suspension under two-photon activation leads to tumour cell death, suggesting the potential of such structures for theranostic applications.