Investigation of a new thermosensitive block copolymer micelle: hydrolysis, disruption, and release

Thermosensitive polymer micelles are generally obtained with block copolymers in which one block exhibits a lower critical solution temperature in aqueous solution. We investigate a different design that is based on the use of one block bearing a thermally labile side group, whose hydrolysis upon heating shifts the hydrophilic-hydrophobic balance toward the destabilization of block copolymer micelles. Atom transfer radical polymerization was utilized to synthesize a series of diblock copolymers composed of hydrophilic poly(ethylene oxide) (PEO) and hydrophobic poly(2-tetrahydropyranyl methacrylate) (PTHPMA). We show that micelles of PEO-b-PTHPMA in aqueous solution can be destabilized as a result of the thermosensitive hydrolytic cleavage of tetrahydropyranyl (THP) groups that transforms PTHPMA into hydrophilic poly(methacrylic acid). The three related processes occurring in aqueous solution, namely, hydrolytic cleavage of THP, destabilization of micelles, and release of loaded Nile Red (NR), were investigated simultaneously using 1H NMR, dynamic light scattering, and fluorescence spectroscopy, respectively. At 80 degrees C, the results suggest that the three events proceed with a similar kinetics. Although slower than at elevated temperatures, the disruption of PEO-b-PTHPMA micelles can take place at the body temperature (approximately 37 degrees C), and the release kinetics of NR can be adjusted by changing the relative lengths of the two blocks or the pH of the solution.     

Stereoselective glycal fluorophosphorylation: synthesis of ADP-2-fluoroheptose, an inhibitor of the LPS biosynthesis

Heptosides are found in important bacterial glycolipids such as lipopolysaccharide (LPS), the biosynthesis of which is targeted for the development of novel antibacterial agents. This work describes the synthesis of a fluorinated analogue of ADP-L-glycero-beta-D-manno-heptopyranose, the donor substrate of the heptosyl transferase WaaC, which catalyzes the incorporation of this carbohydrate into LPS. Synthetically, the key step for the preparation of ADP-2F-heptose is the simultaneous and stereoselective installation of both the fluorine atom at C-2 and the phosphoryl group at C-1 through a selectfluor-mediated (selectfluor=1-chloromethyl-4-fluorodiazoniabicyclo[2.2.2]octane bis(triflate)) electrophilic addition/nucleophilic substitution involving a heptosylglycal. Therefore, we detail in this article 1) the stereoselective preparation of the key intermediates heptosylglycals, 2) the development of a new fluorophosphorylation procedure allowing an excellent beta-gluco stereoselectivity with "all-equatorial" glycals, 3) the synthesis of the target ADP-2F-heptose, and 4) some comments on the contacts observed between the fluorine atom of the final molecule and the protein in the crystallographic structure of heptosyltransferase WaaC.     

De novo synthesis of (+)-isofregenedol

An efficient enantioselective synthesis of (+)-isofregenedol was achieved in 13 steps from commercially available cyclohexene oxide without the use of protecting groups. The tetrahydronaphthalenic core of isofregenedol was obtained via a gold(I)-catalyzed benzannulation recently developed in our laboratory.     

Multifunctional Helicene-Based Ytterbium Coordination Polymer Displaying Circularly Polarized Luminescence,Slow Magnetic Relaxation and Room Temperature Magneto-Chiral Dichroism**

The combination of physical properties sensitive to molecular chirality in a single system allows the observation of fascinating phenomena such as magneto-chiral dichroism (MChD) and circularly polarized luminescence (CPL) having potential applications for optical data readout and display technology. Homochiral monodimensional coordination polymers of Yb^III were designed from a 2,15-bis-ethynyl-hexahelicenic scaffold decorated with two terminal 4-pyridyl units. Thanks to the coordination of the chiral organic chromophore to Yb(hfac)₃ units (hfac⁻=1,1,1,5,5,5-hexafluoroacetylaconate), efficient NIR-CPL activity is observed. Moreover, the specific crystal field around the Yb^III induces a strong magnetic anisotropy which leads to a single-molecule magnet (SMM) behaviour and a remarkable room temperature MChD. The MChD-structural correlation is supported by computational investigations.     

Collective Total Synthesis of Mavacuran Alkaloids through Intermolecular 1,4-Addition of an Organolithium Reagent**

We report a synthetic endeavor towards the highly strained pentacyclic caged framework of the mavacuran alkaloids which culminated with the concise total synthesis of C-fluorocurine, C-profluorocurine, C-mavacurine, normavacurine, 16-epi-pleiocarpamine and taberdivarine H. We designed a strategy involving late-stage construction of the D ring by Michael addition of a vinylic nucleophile to a 2-indolyl acrylate moiety. While the intramolecular Michael addition did not succeed, we were able to perform a diastereoselective unusual intermolecular 1,4-addition of a functionalized vinyl lithium reagent to a readily accessible Michael acceptor with the assistance of the piperidine nitrogen atom through the formation of a complex as suggested by DFT computations. Final cyclization was achieved by nucleophilic substitution to form an ammonium intermediate. The first total syntheses of C-profluorocurine and C-fluorocurine were finalized by the dihydroxylation of C-mavacurine and a pinacol rearrangement, respectively.     

Luminescent Single-Molecule Magnets as Dual Magneto-Optical Molecular Thermometers

Luminescent thermometry allows the remote detection of the temperature and holds great potential in future technological applications in which conventional systems could not operate. Complementary approaches to measuring the temperature aiming to enhance the thermal sensitivity would however represent a decisive step forward. For the first time, we demonstrate the proof-of-concept that luminescence thermometry could be associated with a complementary temperature readout related to a different property. Namely, we propose to take advantage of the temperature dependence of both magnetic (canonical susceptibility and relaxation time) and luminescence features (emission intensity) found in Single-Molecule Magnets (SMM) to develop original dual magneto-optical molecular thermometers to conciliate high-performance SMM and Boltzmann-type luminescence thermometry. We highlight this integrative approach to concurrent luminescent and magnetic thermometry using an air-stable benchmark SMM [Dy(bbpen)Cl] (H₂bbpen=N,N′-bis(2-hydroxybenzyl)-N,N′-bis(2-methylpyridyl)ethyl-enediamine)) exhibiting Dy³⁺ luminescence. The synergy between multiparametric magneto-optical readouts and multiple linear regression makes possible a 10-fold improvement in the relative thermal sensitivity of the thermometer over the whole temperature range, compared with the values obtained with the single optical or magnetic devices.     

An Interlocked Figure-of-Eight Molecular Shuttle

Here is reported the synthesis and characterization of an interlocked figure-of-eight rotaxane molecular shuttle from a dibenzo-24-crown-8 (DB24C8) derivative. This latter bears two molecular chains, whose extremities are able to react together by click chemistry. One of the two substituting chain holds an ammonium function aimed at driving the self-entanglement through the complexation of the DB24C8 moiety. In the targeted figure-of-eight rotaxane, shuttling of the DB24C8 along the threaded axle from the best ammonium station to the weaker binding site triazolium was performed through deprotonation or deprotonation-then-carbamoylation of the ammonium. This way, two discrete co-conformational states were obtained, in which the folding and size of the two loops could be changed.     

Photochemical electrocyclization and leaving group expulsion with a naphthothiophene-2-carboxanilide linked to a chromophore

A naphthiothiophene-2-carboxanilide bearing a leaving group at the C-3 position undergoes efficient electrocyclic ring closure and leaving group expulsion upon direct photolysis. The reaction occurs in the triplet excited state and can be sensitized by thioxanthone. Thioxanthone as chromophore can also be covalently attached to amide nitrogen by a trimethylene linker, and the photoreaction is equally efficient. Quenching studies show that the triplet excitation is localized primarily on the naphthothiophene moiety, due to rapid exothermic energy transfer from the thioxanthone chromophore. Acriflavin dye is capable of sensitizing the photoreaction at 450?nm, but the quantum yield is low in this case.     

Selective Preparation of a Heteroleptic Cyclometallated Ruthenium Complex Capable of Undergoing Photosubstitution of a Bidentate Ligand

Cyclometallated ruthenium complexes typically exhibit red-shifted absorption bands and lower photolability compared to their polypyridyl analogues. They also have lower symmetry, which sometimes makes their synthesis challenging. In this work, the coordination of four N,S bidentate ligands, 3-(methylthio)propylamine (mtpa), 2-(methylthio)ethylamine (mtea), 2-(methylthio)ethyl-2-pyridine (mtep), and 2-(methylthio)methylpyridine (mtmp), to the cyclometallated precursor [Ru(bpy)(phpy)(CH₃CN)₂]⁺ (bpy=2,2′-bipyridine, Hphpy=2-phenylpyridine) has been investigated, furnishing the corresponding heteroleptic complexes [Ru(bpy)(phpy)(N,S)]PF₆ ([ 2 ]PF₆–[ 5 ]PF₆, respectively). The stereoselectivity of the synthesis strongly depended on the size of the ring formed by the Ru-coordinated N,S ligand, with [ 2 ]PF₆ and [ 4 ]PF₆ being formed stereoselectively, but [ 3 ]PF₆ and [ 5 ]PF₆ being obtained as mixtures of inseparable isomers. The exact stereochemistry of the air-stable complex [ 4 ]PF₆ was established by a combination of DFT, 2D NMR, and single-crystal X-ray crystallographic studies. Finally, [ 4 ]PF₆ was found to be photosubstitutionally active under irradiation with green light in acetonitrile, which makes it the first cyclometallated ruthenium complex capable of undergoing selective photosubstitution of a bidentate ligand.     

Experimental chaotic map generated by picosecond laser pulse-seeded electro-optic nonlinear delay dynamics

We describe experimental studies of the dynamical behavior of a recently proposed electro-optic discrete time nonlinear delay oscillator. With appropriate choice of the oscillator loop parameters and external forcing of the dynamics using a pulsed laser source, the system allows for the physical realization of a high dimensional mathematical nonlinear mapping. The dynamical features observed with this new class of discrete time delay oscillator differ significantly from those observed with similar continuous time nonlinear delay feedback oscillators and reveal the intrinsic discrete time nature of the dynamics. We also discuss specific applications to chaos communications using regularly clocked binary data.