Guillaume Delaittre

Adding spatial control to click chemistry: phototriggered Diels-Alder surface (bio)functionalization at ambient temperature.

A photoconjugation strategy based on light-triggered Diels–Alder addition of o-quinodimethanes is compatible with biomolecules and proceeds rapidly at ambient temperature without the need of a catalyst. Spatial control was confirmed by photopatterning of a small-molecule ATRP initiator, a polymer, and a peptide in a time-of-flight secondary-ion mass spectrometry investigation.

Cycloadditions in Modern Polymer Chemistry

Synthetic polymer chemistry has undergone two major developments in the last two decades. About 20 years ago, reversible-deactivation radical polymerization processes started to give access to a wide range of polymeric architectures made from an almost infinite reservoir of functional building blocks. A few years later, the concept of click chemistry revolutionized the way polymer chemists approached synthetic routes. Among the few reactions that could qualify as click, the copper-catalyzed azide-alkyne cycloaddition (CuAAC) initially stood out. Soon, many old and new reactions, including cycloadditions, would further enrich the synthetic macromolecular chemistry toolbox. Whether click or not, cycloadditions are in any case powerful tools for designing polymeric materials in a modular fashion, with a high level of functionality and, sometimes, responsiveness. Here, we wish to describe cycloaddition methodologies that have been reported in the last 10 years in the context of macromolecular engineering, with a focus on those developed in our laboratories. The overarching structure of this Account is based on the three most commonly encountered cycloaddition subclasses in organic and macromolecular chemistry: 1,3-dipolar cycloadditions, (hetero-)Diels-Alder cycloadditions ((H)DAC), and [2+2] cycloadditions. Our goal is to briefly describe the relevant reaction conditions, the advantages and disadvantages, and the realized polymer applications. Furthermore, the orthogonality of most of these reactions is highlighted because it has proven highly beneficial for generating unique, multifunctional polymers in a one-pot reaction. The overview on 1,3-dipolar cycloadditions is mostly centered on the application of CuAAC as the most travelled route, by far. Besides illustrating the capacity of CuAAC to generate complex polymeric architectures, alternative 1,3-dipolar cycloadditions operating without the need for a catalyst are described. In the area of (H)DA cycloadditions, beyond the popular maleimide/furan couple, we present chemistries based on more reactive species, such as cyclopentadienyl or thiocarbonylthio moieties, particularly stressing the reversibility of these systems. In these two greater families, as well as in the last section on [2+2] cycloadditions, we highlight phototriggered chemistries as a powerful tool for spatially and temporally controlled materials synthesis. Clearly, cycloaddition chemistry already has and will continue to transform the field of polymer chemistry in the years to come. Applying this chemistry enables better control over polymer composition, the development of more complicated polymer architectures, the simplification of polymer library production, and the discovery of novel applications for all of these new polymers.

Bio)Molecular Surface Patterning by Phototriggered Oxime Ligation

Making light work of ligation: A novel method utilizes light for oxime ligation chemistry. A quantitative, low-energy photodeprotection generates aldehyde, which subsequently reacts with aminooxy moieties. The spatial control allows patterning on surfaces with a fluoro marker and GRGSGR peptide, and can be imaged by time-of-flight secondary-ion mass spectrometry.

Light-Induced Modular Ligation of Conventional RAFT Polymers†

Making light work of RAFT conjugation: a non-activated RAFT agent at the end of RAFT polymers can readily be coupled with ortho-quinodimethanes (photoenols) in a photo-triggered Diels-Alder reaction under mild conditions without catalyst. The method is universal and opens the door for the conjugation of a large number of RAFT-prepared polymers with photoenol-functionalized (macro)molecules. (RAFT=reversible addition-fragmentation chain transfer.).

Aqueous suspension of amphiphilic diblock copolymer nanoparticles prepared in situ from a water-soluble poly(sodium acrylate) alkoxyamine macroinitiator

The simple, one step synthesis of aqueous suspensions of amphiphilic nanoparticles is presented. Those particles are prepared in the batch heterophase polymerization of styrene or -butyl acrylate, using a water-soluble poly(sodium acrylate) alkoxyamine macroinitiator. The nitroxide-mediated controlled growth of the hydrophobic block leads to the formation of poly(sodium acrylate)--polystyrene or poly(sodium acrylate)--poly(-butyl acrylate) amphiphilic diblock copolymers, able to self-assemble in water simultaneously to the growth step. When the diblock copolymers become strongly asymmetrical, with a short poly(sodium acrylate) block and a long hydrophobic one, the formed hairy nanoparticles are analogous to amphiphilic diblock copolymer crew-cut micelles.

Preparation of Hybrid Latex Particles and Core–Shell Particles Through the Use of Controlled Radical Polymerization Techniques in Aqueous Media

The synthesis of hybrid and core–shell nanoparticles using controlled/ living radical polymerization in aqueous dispersed systems is reviewed. The processes involve emulsion, miniemulsion, and dispersion polymerizations as well as grafting techniques, with the aim of producing submicrometric latex particles with well-defined morphologies that might not be accessible via classical radical polymerization. Those morphologies include organic/inorganic hybrids, nanostructured particles, (nano)capsules, and particles with a hydrophobic core and hydrophilic shell.

Ambient temperature polymer modification by in situ phototriggered deprotection and thiol–ene chemistry

A novel and efficient methodology for the light-triggered release of thiols at ambient temperature is presented, which can be utilized for the in situ modification of polymeric backbones prepared via radical polymerization. Initially, a model reaction on poly(ethylene glycol) methyl ether was examined via size-exclusion chromatography coupled with electrospray ionization-mass spectrometry (SEC/ESI-MS) to establish the photodeprotection feasibility of 2-nitrobenzyl thioether moieties in the presence of variable activators or catalysts employed are Michael-type or radical thiol–ene chemistries, respectively. When 0.01 eq. of dimethylphenylphosphine is employed, disulfide coupling is reduced to its minimum and quantitative phototriggered formation of thiol-capped poly(ethylene glycol) methyl ether species is observed after a 16 hour irradiation period at 320 nm by a low-cost light source. The concept is extended to polymer backbone modification by atom transfer radical polymerization of the novel photosensitive monomer: 2-((3-((2-nitrobenzyl)thio)propanoyl)oxy)ethyl methacrylate containing the 2-nitrobenzyl thioether moiety. Well-defined homopolymers (4700 g·mol−1 ≤ Mn ≤ 20 000 g·mol−1, 1.29 ≤ PDI ≤ 1.40) containing one protected thiol per repeating unit were obtained and, upon a light stimulus (λmax = 320 nm), thiol entities are released along the lateral polymer chain. The photodeprotection process is mapped by exploiting the increased absorbance of photocleaved o-nitrosobenzaldehyde molecules at 345 nm and UV-Vis data suggests a quantitative backbone deprotection after a 16 hour irradiation time period. Further in situ functionalization of polymeric backbone is achieved via base-catalyzed maleimide–thiol addition at ambient temperature and its outcome is evidenced by a re-increased molecular weight in SEC, by virtue of decreased signal intensity of the 2-nitrobenzyl thioether moiety and the appearance of characteristic product protons in NMR spectroscopy (the polymer backbone functionalization is estimated as >90% by NMR analysis).

Cascade Reactions in an All‐Enzyme Nanoreactor

Good things come in small packages! Giant amphiphiles, consisting of a polymeric hydrophobic tail and a horseradish peroxidase head, were simultaneously synthesized and self-assembled into vesicles. During the self-assembly process, glucose oxidase was encapsulated to create enzymatic cascade nanoreactors (see picture; ABTS= 2,2′-azido-bis(3-ethylbenzthiazoline-6-sulfonic acid)).

Efficient Photochemical Approaches for Spatially Resolved Surface Functionalization

Materials interfaces--with a gas, a liquid, or another solid--are highly important for advanced applications. Besides their topological design, controlling interactions at these interfaces is typically realized by tuning the chemical composition of the materials surface. In areas such as nanoscience or biology, it is, however, highly desirable to impart heterogeneously distributed properties. Photopatterning, more than micro- and nanoprinting methods, is often the method of choice for precise functionalization, especially in terms of versatility. Recently, a range of new or rediscovered photochemistry approaches have been applied to precision surface functionalization, with the common aim of increasing efficiency and resolution while concomitantly lowering the amount of required energy. A survey of such methods is presented in this Review, with a focus on those we have explored.

(Ultra)fast catalyst-free macromolecular conjugation in aqueous environment at ambient temperature.

Tailor-made water-soluble macromolecules, including a glycopolymer, obtained by living/controlled RAFT-mediated polymerization are demonstrated to react in water with diene-functionalized poly(ethylene glycol)s without pre- or post-functionalization steps or the need for a catalyst at ambient temperature. As previously observed in organic solvents, hetero-Diels-Alder (HDA) conjugations reached quantitative conversion within minutes when cyclopentadienyl moieties were involved. However, while catalysts and elevated temperatures were previously necessary for open-chain diene conjugation, additive-free HDA cycloadditions occur in water within a few hours at ambient temperature. Experimental evidence for efficient conjugations is provided via unambiguous ESI-MS, UV/vis, NMR, and SEC data.