Syntheses of new difluoromethylene benzoxazole and 1,2,4-oxadiazole derivatives, as potent non-nucleoside HIV-1 reverse transcriptase inhibitors

In an effort to prepare new fluorine-containing compounds, which are active against HIV, several chemical modifications of a series of benzoxazole and 1,2,4-oxadiazole-CF₂CHOHAr derivatives were carried out. The products (9-30) which all have one or two CF₂ groups were tested for activity against HIV-1; they were devoid of significant activity, one of them being cytotoxic.     

Synthesis and photochemical behavior of phosphorus dendrimers containing azobenzene units within the branches and/or on the surface

We describe the synthesis of three series of phosphorus-containing dendrimers having azobenzene derivatives specifically placed at some generations in the interior and/or on the surface. The largest compound obtained possesses 48 azobenzene groups on the surface. Irradiation at 350 nm induces isomerization of the azobenzene groups from the E form to the Z form, whatever their location. The thermal back-isomerization to the E form in the dark at room temperature was observed in all cases. The kinetics of this Z-->E back-isomerization was studied in several cases; the rate is not dependent on the number of azobenzene units or of the generation, when the azobenzene groups are linked to the surface of the dendrimer. A different behavior was observed when the azobenzene groups were located within the framework of the dendrimer.     

Symmetrical and unsymmetrical incorporation of active biological monomers on the surface of phosphorus dendrimers

Phosphorus-containing dendrimers are attractive carriers for the delivery of bioactive molecules due to their very particular architecture, globular shape and chemical and physical properties. Herein we report a simple synthetic approach of ethacrynic acid derivatives loaded-phosphorus dendrimers by symmetrical grafting of ethacrynic acid analogues by nucleophilic substitution of each chlorine of P(S)Cl₂ end groups. We report also for the first time an unsymmetrical grafting of two different phenol derivatives by a selective substitution of one chlorine of P(S)Cl₂ end group followed by the grafting of the second phenol.     

Validity of the Geometric Model of Ovaloid Polymers Based on Simpler Molecules

The shape parameter obtained from the geometric model of Ishihara and Hayashida for ovaloid polymers, together with the scaled-particle theory, are applied to a mixture of methane and ethylene. The results are in good agreement with the experimental values, indicating the validity of the model and suggesting application to other polymer properties.     

Dendrimeric Nanoparticles for Two-Photon Photodynamic Therapy and Imaging: Synthesis,Photophysical Properties,Innocuousness in Daylight and Cytotoxicity under Two-Photon Irradiation in the NIR

The synthesis and the photophysical properties of a new class of fully organic monodisperse nanoparticles for combined two-photon imaging and photodynamic therapy are described. The design of such nanoparticles is based on the covalent immobilization of a dedicated quadrupolar dye that combines excellent two-photon absorbing (2PA) properties, fluorescence and singlet oxygen generation ability, in a phosphorous-based dendrimeric architecture. First, a bifunctional quadrupolar dye bearing two different grafting moieties, a phenol function and an aldehyde function, was synthesized. It was then covalently grafted through its phenol function to a phosphorus-based dendrimer scaffold of generation 1. The remaining aldehyde functions were then used to continue the dendrimer synthesis up to generation 2, introducing finally 24 water-solubilizing triethyleneglycol chains at its periphery. A dendrimer confining 12 photoactive quadrupolar units in its inner scaffold and showing water solubility was thus obtained. Interestingly, the G1 and G2 dendrimers retain some fluorescence as well as significant singlet oxygen production efficiencies while they were found to show very high 2PA cross-sections in a broad range of the NIR biological spectral window. Hydrophilic dendrimer G2 was tested in vitro on breast cancer cells, first in one- and two-photon microscopy, which allowed for visualization of their cell internalization, then in two-photon photodynamic therapy. While being nontoxic in the dark and, more importantly, under exposure to daylight, dendrimer G2 proved to be a very efficient cell-death inducer only under two-photon irradiation in the NIR.     

Method of Calculation of a Shape Parameter for Ovaloid Molecules

The nonsphericity parameter γrelated to the Isihara shape factor for ovaloid polymers f by the relation f = (γ/4) + (1/4) is calculated through an expansion of the radius of the molecule in spherical harmonics. The limitations of the method when applied to polymers with high f are discussed.     

Three dimensional imaging using secondary ion mass spectrometry and atomic force microscopy

With the breakthroughs in lateral resolution with regards to secondary ion mass spectroscopy in recent years, new areas of research with much promise have opened up to the scientific community. Even though the much improved lateral resolution of 50 nm can effectively deliver more accurate 3D-images, the traditional 3D reconstructions, consisting of compiling previously acquired successive secondary ion mass spectrometry images into a 3D-stack, do not represent the real localized chemical distribution of the sputtered volume. Based on samples initially analyzed on the Cameca NanoSIMS 50 instrument, this paper portrays the advantages of combining the topographical information from atomic force microscopy and the chemical information from secondary ion mass spectrometry. Taking account of the roughness evolution within the analyzed zone, 3D reconstructions become a lot more accurate and allow an easier interpretation of results. On the basis of an Al/Cu sample, a comparison between traditional 3D imaging and corrected 3D reconstructions is given and the advantages of the newly developed 3D imaging method are explained.     

A Preparative Synthesis of 1-Amino-3-hydroxypropylphosphonic Acid (Phosphonic Analogue of Homoserine)

A novel procedure for the preparation of the phosphonic analogue of homoserine is described starting from the commercially available 4-acetoxy-azetidin-2-one.