Jean-Marc Schumers

Light-Responsive Block Copolymers

Stimuli-responsive polymers are the subject of intense research because they are able to show responses to various environmental changes. Among those stimuli, light has attracted much attention since it can be localized in time and space and it can also be triggered from outside of the system. In this paper, we review light-responsive block copolymers (LRBCs) that combine characteristic features of block copolymers, e.g., self-assembly behavior, and light-responsive systems. The different photo-responsive moieties that have been incorporated so far in block copolymers as well as the proposed applications are discussed.

A versatile strategy for the synthesis of block copolymers bearing a photocleavable junction

Various block copolymers in which the blocks are held together by a photocleavable junction have been synthesized via a one-pot simultaneous ATRP–CuAAC “click” reaction process, and their easy photocleavage has been demonstrated.

Highly beta-(E)-selective hydrosilylation of terminal and internal alkynes catalyzed by a (IPr)Pt(diene) complex.

The regioselective hydrosilylation of terminal and internal alkynes catalyzed by the novel (IPr)Pt(AE) ( 7) (IPr = bis(2,6-diisopropylphenyl)imidazo-2-ylidene, AE = allyl ether) complex is presented. The (IPr)Pt(AE) catalyst displays enhanced activity and regioselectivity for the hydrosilylation of terminal and internal alkynes with low catalyst loading (0.1 to 0.05 mol %) when compared to the parent (IPr)Pt(DVDS) complex ( 6) (DVDS = divinyltetramethyldisiloxane). The reaction leads to exquisite regioselectivity in favor of the cis-addition product on the less hindered terminus of terminal and internal alkynes. The solvent effects were examined for the difficult hydrosilylation of benzylpropargyl ether. In light of the observed product distribution and kinetic data, a mechanistic scheme is proposed involving two competing catalytic cycles. One cycle leads to high regioselectivities while the other, having lost the stereodirecting IPr carbene ligand, displays low regiocontrol and activities. The importance of this secondary catalytic cycle is either caused by the strong coordinating ability of the alkyne or by the low reactivity of the silane or both.

Self-Assembling Doxorubicin−Tocopherol Succinate Prodrug as a New Drug Delivery System: Synthesis, Characterization, and in Vitro and in Vivo Anticancer Activity

Self-assembled prodrugs forming nanoaggregates are a promising approach to enhance the antitumor efficacy and to reduce the toxicity of anticancer drugs. To achieve this goal, doxorubicin was chemically conjugated to d-α-tocopherol succinate through an amide bond to form N-doxorubicin-α-d-tocopherol succinate (N-DOX-TOS). The prodrug self-assembled in water into 250 nm nanostructures when stabilized with d-α-tocopherol poly(ethylene glycol) 2000 succinate. Cryo-TEM analysis revealed the formation of nanoparticles with a highly ordered lamellar inner structure. NMR spectra of the N-DOX-TOS nanoparticles indicated that N-DOX-TOS is located in the core of the nanoparticles while PEG chains and part of the tocopherol are in the corona. High drug loading (34% w/w) and low in vitro drug release were achieved. In vitro biological assessment showed significant anticancer activity and temperature-dependent cellular uptake of N-DOX-TOS nanoparticles. In vivo, these nanoparticles showed a greater antitumor efficacy than free DOX. N-DOX-TOS nanoparticles might have the potential to improve DOX-based chemotherapy.

Tocol modified glycol chitosan for the oral delivery of poorly soluble drugs

The aim of this study was to develop tocol derivatives of chitosan able (i) to self-assemble in the gastrointestinal tract and (ii) to enhance the solubility of poorly soluble drugs. Among the derivatives synthesized, tocopherol succinate glycol chitosan (GC-TOS) conjugates spontaneously formed micelles in aqueous solution with a critical micelle concentration of 2 μg mL(-1). AFM and TEM analysis showed that spherical micelles were formed. The GC-TOS increased water solubility of 2 model class II drugs. GC-TOS loading efficiency was 2.4% (w/w) for ketoconazole and 0.14% (w/w) for itraconazole, respectively. GC-TOS was non-cytotoxic at concentrations up to 10 mg mL(-1). A 3.4-fold increase of the apparent permeation coefficient of ketoconazole across a Caco-2 cell monolayer was demonstrated. Tocol polymer conjugates may be promising vehicles for the oral delivery of poorly soluble drugs.

Functionalized Nanoporous Thin Films From Photocleavable Block Copolymers

A polystyrene-block-poly(ethylene oxide) block copolymer bearing a photocleavable junction between the blocks is used to form nanoporous thin films with carboxylic acid functions homogeneously distributed on the pore walls. The presence of the carboxylic acid groups is evidenced by fluorescence spectroscopy after their reaction with a diazomethane functionalized fluorescent dye. In addition, the initial light-responsive thin film, acting as a photoresist, can be easily patterned to selectively generate porosity in predetermined areas. In that way, fluorescent patterns can be obtained as evidenced by fluorescent microscopy.

Photo-induced micellization of block copolymers bearing 4,5-dimethoxy-2-nitrobenzyl side groups

The synthesis of photocleavable poly(dimethoxynitrobenzyl acrylate)-block-polystyrene block copolymers is described. The UV irradiation of these block copolymers, dissolved in a good solvent for both blocks, selectively cleaves the dimethoxynitrobenzyl protecting groups, leading to carboxylic acid moieties. Since the resulting hydrophilic poly(acrylic acid) block is insoluble in the solvent used, self-assembly of the diblocks into micelles is observed. This light-induced micellization process is further used to trap dyes into the core of the micelles.

Amine-functionalized nanoporous thin films from a poly(ethylene oxide)-block-polystyrene diblock copolymer bearing a photocleavable o-nitrobenzyl carbamate junction

The synthesis of a poly(ethylene oxide)-block-polystyrene (PEO-b-PS) diblock copolymer bearing an o-nitrobenzyl carbamate junction is reported via a one-pot atom transfer radical polymerization (ATRP)–copper(I)-catalyzed azide–alkyne cycloaddition (CuAAC). The accordingly obtained block copolymer was self-assembled into thin films showing, after solvent annealing, ordered PEO cylinders oriented normal to the film surface and embedded in a PS matrix. In the next step, the easy photocleavage of the o-nitrobenzyl carbamate junction and the subsequent removal of the PEO nanophase were demonstrated. This led to amine-functionalized nanoporous PS thin films as evidenced by the successful coupling of a fluorescent dye bearing a carboxylic acid group. The possibility to obtain fluorescent nanopores was then further exploited to pattern the films using a photolithographic mask.

Pore‐Functionalized Nanoporous Materials Derived from Block Copolymers

This review deals with nanoporous materials made from the self-assembly of block copolymers with a special interest in the chemical functions covering the surface of their nanopores. A detailed overview of the existing methods and strategies to generate well-defined organic functional groups covering the surface of the pore walls is provided. This further enables to finely tune the affinity of the pore walls and to perform well-defined chemical reactions onto them, which is essential for further dedicated applications.

Tuning the morphology of triblock terpoly(2-oxazoline)s containing a 2-phenyl-2-oxazoline block with varying fluorine content

The formation of nanostructures in triblock terpolymers consisting of poly[2-ethyl-2-oxazoline-block-2-(1-ethylpentyl)-2-oxazoline-block-2-(Xfluorophenyl)-2-oxazoline] (X = di, tri, tetra and penta) was investigated in water. For this purpose a gradually increasing degree of fluorination was introduced in the molecular structures and its influence on the self-assembly was studied. It can be demonstrated that the basic form of aggregation of these systems resembles rod-like micelles, which tend, upon introduction of fluorinated blocks, to aggregate first into 2-dimensional and later into 3-dimensional super-aggregates. In the case of di- and pentafluorinated terpolymers well-defined structures were observed, which represent likely intermediate, stable transient structures formed during an assumed rod-to-vesicle transition. DLS and cryo-TEM were utilized to analyze the structural features of these nanostructures and a model for their further assembly into super-structures was developed.