A disulfide intercalator toolbox for the site-directed modification of polypeptides.

A disulfide intercalator toolbox was developed for site-specific attachment of a broad variety of functional groups to proteins or peptides under mild, physiological conditions. The peptide hormone somatostatin (SST) served as model compound for intercalation into the available disulfide functionalization schemes starting from the intercalator or the reactive SST precursor before or after bioconjugation. A tetrazole-SST derivative was obtained that undergoes photoinduced cycloaddition in mammalian cells, which was monitored by live-cell imaging.

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.

Visible-Light-Induced Click Chemistry.

A rapid and catalyst-free cycloaddition system for visible-light-induced click chemistry is reported. A readily accessible photoreactive 2H-azirine moiety was designed to absorb light at wavelengths above 400 nm. Irradiation with low-energy light sources thus enables efficient small-molecule synthesis with a diverse range of multiple-bond-containing compounds. Moreover, in order to demonstrate the efficiency of the current approach, quantitative ligation of the photoactivatable chromophore with functional polymeric substrates was performed and full conversion with irradiation times of only 1 min at ambient conditions was achieved. The current report thus presents a highly efficient method for applications involving selective cycloaddition to electron-deficient multiple-bond-containing materials.

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.).

α,ω-Reactive Building Blocks Based on a Dual Functional RAFT Agent for Thermal and Light-Induced Ligation.

A dual functional chain transfer agent (CTA) capable of highly efficient sequential thermal and photoinduced ligation, generating α,ω-functional polymers, is introduced. The newly designed CTA (1-(4-((2-formyl-3-methyl phenoxy)methyl)phenyl)ethyl (diethoxyphosphoryl)methane dithioate) fuses thermally triggered hetero Diels-Alder chemistry with rapid light-induced photoenol chemistry. The versatility of the CTA is exemplarily demonstrated via the preparation of an amphiphilic triblock quaterpolymer poly(isoprene-co-styrene)-block-poly(ethyl acrylate)-block-poly(ethylene oxide) (P(I-co-S)-b-PEA-b-PEO). Subsequent to the homopolymerization of ethyl acrylate (PEA), a Cp-functional poly(isoprene-co-styrene) (P(I-co-S)) is conjugated with the electron-deficient C═S double bond (dienophile) of the CTA end group, generating a P(I-co-S)-b-PEA diblock terpolymer. The triblock quaterpolymer P(I-co-S)-b-PEA-b-PEO is generated by photoligation of a macromolecular dienophile, i.e., the fumarate-terminated poly(ethylene oxide) (PEO-fum) to the photoenol-functional P(I-co-S)-b-PEA. The new dual functional ligation RAFT agent constitutes a technology platform for generating α,ω-reactive building blocks from one single chain transfer agent.

Photo-induced sequence defined macromolecules via hetero bifunctional synthons.

We report the first photochemical protocol for the generation of sequence defined macromolecules employing two hetero bifunctional photoreactive synthons, exploiting the orthogonal nature of photochemical - via the use of caged dienes - and thermally driven ligation protocols. We demonstrate that the iterative alternating synthon addition to an initial bifunctional core under irradiation at ambient temperature enables the generation of a macromolecule with up to 10 units (M = 3231.58 g mol(-1), D = 1.00). The resulting macromolecules are monodisperse and feature absolute chain end fidelity. The unit-by-unit construction of the macromolecule is evidenced by Nuclear Magnetic Resonance Spectroscopy, Electrospray Ionization Mass Spectrometry and Size Exclusion Chromatography. The fundamental principle demonstrated herein paves the way for employing photochemical strategies for the design of sequence defined polymers.

Fluorescent polymers from non-fluorescent photoreactive monomers.

A facile, fast and ambient-temperature avenue towards highly fluorescent polymers is introduced via polymerizing non-fluorescent photoreactive monomers based on light-induced NITEC chemistry, providing a platform technology for fluorescent polymers. The resulting polypyrazolines were analyzed in depth and the photo-triggered step-growth process was monitored in a detailed kinetic study.

Adaptable hetero Diels-Alder networks for fast self-healing under mild conditions.

A novel adaptable network based on the reversible hetero Diels-Alder reaction of a cyanodithioester and cyclopentadiene is presented. Reversible between 50-120 °C, the adjustable and self-healing features of the network are evidenced via temperature dependent rheology experiments and repetitive tensile tests whereas the network's chemical structure is explored by temperature dependent (1) H MAS-NMR spectroscopy.

Photochemical Design of Functional Fluorescent Single-Chain Nanoparticles.

We report the facile ambient temperature generation of size tunable and well-defined (pro)fluorescent single-chain nanoparticles (SCNPs) via the photoinduced nitrile imine intramolecular cross-ligation of linear precursor polymers, constituting a platform technology as novel imaging agents. A set of three linear precursor polymers (Mn ≈ 14000 g mol-1, D ≈ 1.25) was synthesized via nitroxide-mediated statistical copolymerization of styrene and 4-(chloromethyl)styrene (CMS), followed by a postpolymerization modification of the resulting copolymer installing protected maleimide (PG-Mal) as well as tetrazole (Tet) moieties. The tetrazole content (% Tet) along the lateral polymer chains was varied between 12 and 24% in order to preselect not only the size of the corresponding SCNPs, but also their fluorescence and reactive properties. Finally, the applicability of the profluorescent SCNPs for fluorescence labeling was demonstrated utilizing residual surface expressed Tet moieties on the SCNPs surface in a reaction with maleimide functional polymeric microspheres. The (pro)fluorescent single-chain nanoparticles were in-depth characterized by 1H NMR spectroscopy, dynamic light scattering (DLS), size exclusion chromatography (SEC), and atomic force microscopy (AFM), as well as UV/vis and fluorescence spectroscopy.

Photo-patterning of non-fouling polymers and biomolecules on paper.

Functional cellulose substrates with tetrazole moieties are generated to serve as universal platforms for the spatio-temporal immobilization of synthetic ultra-low fouling polymer brushes and protein species via a nitrile imine-mediated tetrazole-ene cycloaddition (NITEC)-based protocol. Poly(carboxybetaine acrylamide) brushes are grafted from initiators photo-patterned by NITEC utilizing single electron transfer living radical polymerization. Streptavidin is photo-immobilized with remarkable efficiency, opening the possibility to generate new materials for biomedical and biosensing applications.

Controlled cell adhesion on poly(dopamine) interfaces photopatterned with non-fouling brushes.

Bioinspired poly(dopamine) (PDA) films are merged with antifouling poly(MeOEGMA) brushes utilizing a nitrile imine-mediated tetrazole-ene cycloaddition (NITEC)-based phototriggered surface encoding protocol. The antifouling brushes were photopatterned on PDA surfaces, leading cells to form confluent layers in the non-irradiated sections, while no adhesion occurred on the brushes resulting in a remarkably precise cell pattern. The presented strategy paves the way for the design of tailor-made patterned cell interfaces.