Synthesis, characterization and applications of pH-responsive core-shell-corona micelles in water

Doctoral thesis (2007)

ABC triblock copolymers self-organize into a wide variety of supramolecular structures in the bulk. However, their associative behavior in selective solvents has scarcely been studied. Within the search ... [more ▼]

ABC triblock copolymers self-organize into a wide variety of supramolecular structures in the bulk. However, their associative behavior in selective solvents has scarcely been studied. Within the search for new stimuli-responsive supramolecular architectures, our attention focused on a pH-responsive polystyrene-b-poly(2-vinylpyridine)-b-poly(ethylene oxide) (PS-b-P2VP-b-PEO) triblock copolymer. In addition to the synthesis of monodisperse spherical core-shell-corona (CSC) micelles, the reversibility and the cooperativity of the response to pH variations were studied, morphological transitions were induced and multi-responsive micellar gels were prepared. The micellization mechanism, the structure, the responsiveness and the internal organization of these new nanomaterials were investigated using a combination of transmission electronic microscopy, atomic force microscopy, light scattering, small-angle neutron and X-ray scattering, nuclear magnetic resonance and rheology. Finally, efforts were geared towards potential applications. The ability of PS-b-P2VP-b-PEO CSC micelles to encapsulate and release hydrophobic species was probed and gold nanoparticles were successfully synthesized within the P2VP layer of spherical and cylindrical micelles, which acted as nanoreactors. [less ▲]

Synthesis, characterization, and miscibility of caprolactone random copolymers

in Macromolecules (1986), 19(7), 1828-1838

The ring-opening polymerization and copolymerization of ε-caprolactone, ε-methyl-ε-caprolactone, β,δ-methyl-ε-caprolactone (mixed isomers), and L-lactide using aluminum isopropoxide as initiator were ... [more ▼]

The ring-opening polymerization and copolymerization of ε-caprolactone, ε-methyl-ε-caprolactone, β,δ-methyl-ε-caprolactone (mixed isomers), and L-lactide using aluminum isopropoxide as initiator were investigated. The chain propagation proceeds through a living anionic type coordinated insertion mechanism. The kinetic features of this process are reported. The experimental monomer reactivity ratios indicate that ε-caprolactone and its methyl derivatives yield random copolyesters. However, the ε-caprolactone/L-lactide pair exhibits a departure from randomness with the preferred incorporation of L-lactide units. The thermal properties of the copolymers were investigated by differential scanning calorimetry. It was found that the crystallization of ε-caprolactone units is limited, in all cases, to copolymers which are rich in this sort of unit. At the same time, the crystallization of L-lactide units was observed in copolymers with high concentrations of this comonomer. Analysis of the melting point depreasion data of the copolymers indicates that the L-lactide units are almost completely rejected from the caprolactone crystals, whereas about 50% of the ε-methyl-ε-caprolactone and δ,δ-methyl-ε-caprolactone comonomer units are incorporated into the ε-caprolactone crystals due to an obvious structural similarity. Finally, poly(ε-caprolactone-co-ε-methyl-ε-caprolactone) samples are miscible with poly(viny1 chloride) (PVC) whatever the composition of the copolymer and the composition of the blend, whereas poly(εt-caprolactone-co-L-lactide) samples are miscible with PVC uniquely for copolymer L-lactide contents equal to or smaller than 40 wt %. In all cases where miscibility was found, a negative thermodynamic interaction parameter was computed. [less ▲]

Synthesis, hydrolysis, biochemical and theoretical evaluation of 1,4-bis(alkoxycarbonyl)azetidin-2-ones as potential elastase inhibitors

in Tetrahedron (2002), 58(12), 2423-2433

A series of 1,4-bis(alkoxycarbonyl)azetidin-2-ones, designed as potential suicide-inhibitors of serine proteases, has been synthesized and evaluated against porcine pancreatic elastase (PPE). The most ... [more ▼]

A series of 1,4-bis(alkoxycarbonyl)azetidin-2-ones, designed as potential suicide-inhibitors of serine proteases, has been synthesized and evaluated against porcine pancreatic elastase (PPE). The most active compound (K(i)similar to10 muM; reversible inhibitor) was equipped with phenethyloxycarbonyl and benzyloxycarbonyl side-chains at positions N1 and C4, respectively, with the (S)-configuration. H-1 NMR spectroscopic analysis of the reaction mixtures showed that the ester function is preferentially hydrolyzed, in both chemical and enzyme-catalyzed reactions, with regard to the azetidinone and urethane functions. Considering the three potentially sensitive carbonyl functions and the two stereoisomers, ab initio calculations were performed to determine the energetic barriers required to reach the transition state structures of hydrolysis in a model of the enzyme pocket. (C) 2002 Elsevier Science Ltd. All rights reserved. [less ▲]

Synthesis, purification and initial structural characterization of octarellin, a de novo polypeptide modelled on the alpha/beta-barrel proteins

in Protein Engineering (1990), 3(4), 259-66

We have attempted to construct an artificial polypeptide that folds like the eight-stranded parallel beta-barrel structures. Our approach consists of repeating eight times a unit peptide designed to adopt ... [more ▼]

We have attempted to construct an artificial polypeptide that folds like the eight-stranded parallel beta-barrel structures. Our approach consists of repeating eight times a unit peptide designed to adopt a 'beta-strand/alpha-helix' pattern. A first 'test' sequence for this structural unit was deduced from a series of parameters defined after an analysis of three natural alpha/beta-barrel proteins and including principally the lengths of the secondary structure elements, the alpha/beta packing and the fitting on average Garnier profiles. The gene encoding this structural unit was synthesized, cloned and expressed in Escherichia coli either as a monomer or as direct repeats of 2-12 units. Preliminary structural characterization of the 7-, 8- and 9-fold unit polypeptides by circular dichroism measurements indicates the presence of the predicted amount of alpha-helix in the three proteins. Further analysis by urea-gradient gel electrophoresis demonstrates that, in the conditions tested, only the 8-fold unit polypeptide forms a compact structure through a cooperative and rapid two-state folding transition involving long-range molecular interactions. [less ▲]

Synthesis, quality control and in vivo evaluation of [I-123] rhTIMP-2, a potential tumour-imaging agent

in Journal of Labelled Compounds & Radiopharmaceuticals (2005), 48(5), 387-396

Matrix metalloproteinases (MMPs) are enzymes involved in the turnover of the extracellular matrix. Their overexpression in tumours may provide a target for diagnostic imaging by using labelled MMP ... [more ▼]

Matrix metalloproteinases (MMPs) are enzymes involved in the turnover of the extracellular matrix. Their overexpression in tumours may provide a target for diagnostic imaging by using labelled MMP inhibitors. MMPs are inhibited by endogenous tissue inhibitors of metalloproteinases (TIMPs). The enhanced production of MT1-MMP, located on the surface of cells within or in the direct vicinity of the tumour, and the high affinity interaction between TIMP-2 and MT1-MMP suggested that TIMP-2 could be a potential agent for non-invasive monitoring of cancer MMP levels, diagnosis of primary and secondary tumours and tumour response to MMP inhibitor therapy. There is also evidence that I-125-rhTIMP-2 internalizes, which is an important feature for its possible use as a radiotherapeuticum if labelled with I-131. Labelling of rhTIMP-2 was performed using the iodogen method resulting in a radiochemical yield of 51.1 +/- 11.8% (n = 5) and a radiochemical purity of > 98%. The trichloroacetic acid (TCA) precipitability of I-123 rhTIMP-2 was 95.2%. SDS-PAGE confirmed the correct size (21 kDa) of the purified I-123 rhTIMP-2 without degradation. HPLC showed one radioactive peak with a retention time corresponding to the nonlabelled rhTIMP-2. In vivo biodistribution showed no long-term accumulation in organs and the possibility to accumulate in the tumour. These results show the potential of I-123 rhTIMP-2 as tumour-imaging agent. Copyright (c) 2005 John Wiley [less ▲]

Synthesis: tension-type headache mechanisms

in Olesen, J.; Tfelt-Hansen, P.; Welch, K. M. A. (Eds.) The Headaches (1999)

Synthetic and mechanistic inputs of photochemistry into the bisacetylacetonatocobalt- mediated radical polymerization of n-butyl acrylate and vinyl acetate

in Polymer Chemistry (2012), 3(7), 1856-1866

The input of photochemistry to the Co(acac)2 mediated radical polymerization (CMRP) of n-butyl acrylate and vinyl acetate is investigated for the first time. Upon UV irradiation, photoinitiators are able ... [more ▼]

The input of photochemistry to the Co(acac)2 mediated radical polymerization (CMRP) of n-butyl acrylate and vinyl acetate is investigated for the first time. Upon UV irradiation, photoinitiators are able to initiate the n-butyl acrylate polymerization that remains controlled up to very high molar masses (>4 × 106 g mol−1) with low polydispersities. The photoinitiator as well as the irradiation time must be appropriately chosen to reach acceptable initiator efficiencies while maintaining an optimal control over the polymerization. Laser flash photolysis experiments were then carried out to evidence the addition of alkyl and phosphonyl radicals onto Co(acac)2 and to determine the rate constants (kdeact) of these addition reactions that were still lacking. Finally, both kinetics of polymerization and spin-trapping experiments have evidenced that the C–Co bond at the extremity of the dormant polymer chains can be easily photocleaved. UV irradiation can therefore be considered as an additional lever for tuning the reactivity of the CMRP process mediated by Co(acac)2. [less ▲]

Synthetic aperture co-phasing and co-alignment using an external reference source

in Proceedings of ICSO 2006 (2006, June 27)

A breadboard set-up has demonstrated a concept of co-phasing and co-alignment based on an external reference source for synthetic aperture telescopes applications. These types of systems can be extremely ... [more ▼]

A breadboard set-up has demonstrated a concept of co-phasing and co-alignment based on an external reference source for synthetic aperture telescopes applications. These types of systems can be extremely valuable in order to perform coarse re-alignment of synthetic aperture telescope, following thermo-elastic deformation and deployment effects in space flight environments. [less ▲]

Synthetic Biomedical Polymers (Part B)

Poster (1991, May 31)

Synthetic Biomedical Polymers. Part A. a. "Original way to the macromolecular engineering of polyesters : polylactides and poly e-caprolactone". b. "Their formulation and application as embolic material

Poster (1991, January 16)