UV‐Induced Tetrazole‐Thiol Reaction for Polymer Conjugation and Surface Functionalization

A UV‐induced 1,3‐dipolar nucleophilic addition of tetrazoles to thiols is described. Under UV irradiation the reaction proceeds rapidly at room temperature, with high yields, without a catalyst, and in both polar protic and aprotic solvents, including water. This UV‐induced tetrazole‐thiol reaction was successfully applied for the synthesis of small molecules, protein modification, and rapid and facile polymer–polymer conjugation. The reaction has also been demonstrated for the formation of micropatterns by site‐selective surface functionalization. Superhydrophobic–hydrophilic micropatterns were successfully created by sequential modifications of a tetrazole‐modified porous polymer surface with hydrophobic and hydrophilic thiols. A biotin‐functionalized surface could be fabricated in aqueous solutions under long‐wavelength UV irradiation.     

UV‐Induced Disulfide Formation and Reduction for Dynamic Photopatterning

UV‐induced disulfide formation (UV‐DF) and disulfide reduction (UV‐DR) reactions for surface functionalization and dynamic photopatterning are presented. Both photochemical reactions allow for the spatially and temporally controlled, reversible transition between thiol‐ and disulfide‐functionalized surfaces. The dynamic photopatterning strategy was demonstrated by the UV‐induced attachment, exchange, and detachment on thiol‐modified substrates.     

Thiol–Yne Click Reactions on Alkynyl–Dopamine‐Modified Reduced Graphene Oxide

The large‐scale preparation of graphene is of great importance due to its potential applications in various fields. We report herein a simple method for the simultaneous exfoliation and reduction of graphene oxide (GO) to reduced GO (rGO) by using alkynyl‐terminated dopamine as the reducing agent. The reaction was performed under mild conditions to yield rGO functionalized with the dopamine derivative. The chemical reactivity of the alkynyl function was demonstrated by post‐functionalization with two thiolated precursors, namely 6‐(ferrocenyl)hexanethiol and 1H,1H,2H,2H‐perfluorodecanethiol. X‐ray photoelectron spectroscopy, UV/Vis spectrophotometry, Raman spectroscopy, conductivity measurements, and cyclic voltammetry were used to characterize the resulting surfaces.     

Modular Thiol–Ene Chemistry Approach towards Mesoporous Silica Monoliths with Organically Modified Pore Walls

The surface modification of mesoporous silica monoliths through thiol–ene chemistry is reported. First, mesoporous silica monoliths with vinyl, allyl, and thiol groups were synthesized through a sol–gel hydrolysis–polycondensation reaction from tetramethyl orthosilicate (TMOS) and vinyltriethoxysilane, allyltriethoxysilane, and (3‐mercaptopropyl)trimethoxysilane, respectively. By variation of the molar ratio of the comonomers TMOS and functional silane, mesoporous silica objects containing different amounts of vinyl, allyl, and thiol groups were obtained. These intermediates can subsequently be derivatized through radical photoaddition reactions either with a thiol or an olefin, depending on the initial pore wall functionality, to yield silica monoliths with different pore‐wall chemistries. Nitrogen sorption, small‐angle X‐ray scattering, solid‐state NMR spectroscopy, elemental analysis, thermogravimetric analysis, and redox titration demonstrate that the synthetic pathway influences the morphology and pore characteristics of the resulting monoliths and also plays a significant role in the efficiency of functionalization. Moreover, the different reactivity of the vinyl and allyl groups on the pore wall affects the addition reaction, and hence, the degree of the pore‐wall functionalization. This report demonstrates that thiol–ene photoaddition reactions are a versatile platform for the generation of a large variety of organically modified silica monoliths with different pore surfaces.     

Preparation of Reactive Three‐Dimensional Microstructures via Direct Laser Writing and Thiol‐ene Chemistry

Three‐dimensional microstructures are fabricated employing the direct laser writing process and radical thiol‐ene polymerization. The resin system consists of a two‐photon photoinitiator and multifunctional thiols and olefins. Woodpile photonic crystals with 22 layers and a rod distance of 2 μm are fabricated. The structures are characterized via scanning electron microscopy and focused ion beam milling. The thiol‐ene polymerization during fabrication is verified via infrared spectroscopy. The structures are grafted in a subsequent thiol‐Michael addition reaction with different functional maleimides. The success of the grafting reaction is evaluated via laser scanning microscopy and X‐ray photoelectron spectroscopy. The grafting density is calculated to be close to 200 molecules μm⁻².     

Tailored Thiol‐Functional Polyamides: Synthesis and Functionalization

In this article, a synthetic concept for the preparation of polyamides with functional side groups is described. First, the synthesis of a bis(thiolactone) monomer is shown in a concise three‐step route from itaconic acid and DL‐homocysteine thiolactone. The reactivity of the resulting bis(thiolactone) toward hexyl amine is examined. Next, the bis(thiolactone) is reacted as A,A‐type monomer with different B,B‐type comonomers (1,12‐diaminododecane and 1,3‐bis(aminopropyl)tetramethyldisiloxane). Ring opening of the thiolactones by the diamines leads to polyamides with pendant thiol groups. Using two diamines in different ratios, the properties of the resulting polyamides are tuned (thermal properties are determined) and different molecular weights are acquired. Subsequently, the thiol groups are reacted with methyl acrylate via Michael addition to functionalize the polyamides. Functionalization of thiol‐functional polyamides using poly(ethylene glycol) monomethyl ether (mPEG) acrylates ( = 480 and 1700 g mol⁻¹) results in water‐soluble amphiphilic poly­amides with molecular weights higher than 10 000 g mol⁻¹.

     

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.     

UV‐Light‐Induced Hydrogen Transfer in Guanosine–Guanosine Aggregates

Aggregates of a lipophilic guanine (G) derivative have been studied in n‐hexane by femtosecond‐to‐microsecond UV‐visible broadband transient absorption, stationary infrared and UV‐visible spectroscopy and by quantum chemical calculations. We report the first time‐resolved spectroscopic detection of hydrogen transfer in GG aggregates, which leads to (G?H) ^. radicals by means of G⁺G^? charge transfer followed by proton transfer. These radicals show a characteristic electronic spectrum in the range 300–550 nm. The calculated superimposed spectrum of the species that result from NH???N proton transfer agrees best with the experimental spectrum.     

Thiol–Ene Click Chemistry

Following Sharpless′ visionary characterization of several idealized reactions as click reactions, the materials science and synthetic chemistry communities have pursued numerous routes toward the identification and implementation of these click reactions. Herein, we review the radical‐mediated thiol–ene reaction as one such click reaction. This reaction has all the desirable features of a click reaction, being highly efficient, simple to execute with no side products and proceeding rapidly to high yield. Further, the thiol–ene reaction is most frequently photoinitiated, particularly for photopolymerizations resulting in highly uniform polymer networks, promoting unique capabilities related to spatial and temporal control of the click reaction. The reaction mechanism and its implementation in various synthetic methodologies, biofunctionalization, surface and polymer modification, and polymerization are all reviewed.     

Localized Template‐Driven Functionalization of Nanoparticles by Dynamic Combinatorial Chemistry

We have developed a method for the localized functionalization of gold nanoparticles using imine‐based dynamic combinatorial chemistry. By using DNA templates, amines were grafted on the aldehyde‐functionalized nanoparticles only if and where the nanoparticles interacted with the template molecules. Functionalization of the nanoparticles was controlled solely by the DNA template; only amines capable of interacting with DNA were bound to the surface. Interestingly, even though our libraries contained only a handful of simple amines, the DNA sequence influenced their attachment to the surface. Our method opens up new opportunities for the synthesis of multivalent, nanoparticle‐based receptors for biomacromolecules.     

Clickable Nucleic Acids: Sequence‐Controlled Periodic Copolymer/Oligomer Synthesis by Orthogonal Thiol‐X Reactions

Synthetic polymer approaches generally lack the ability to control the primary sequence, with sequence control referred to as the holy grail. Two click chemistry reactions were now combined to form nucleobase‐containing sequence‐controlled polymers in simple polymerization reactions. Two distinct approaches are used to form these click nucleic acid (CNA) polymers. These approaches employ thiol–ene and thiol‐Michael reactions to form homopolymers of a single nucleobase (e.g., poly(A)_n) or homopolymers of specific repeating nucleobase sequences (e.g., poly(ATC)_n). Furthermore, the incorporation of monofunctional thiol‐terminated polymers into the polymerization system enables the preparation of multiblock copolymers in a single reaction vessel; the length of the diblock copolymer can be tuned by the stoichiometric ratio and/or the monomer functionality. These polymers are also used for organogel formation where complementary CNA‐based polymers form reversible crosslinks.     

Photocontrolled On‐Surface Pseudorotaxane Formation with Well‐Ordered Macrocycle Multilayers

The photoinduced pseudorotaxane formation between a photoresponsive axle and a tetralactam macrocycle was investigated in solution and on glass surfaces with immobilized multilayers of macrocycles. In the course of this reaction, a novel photoswitchable binding station with azobenzene as the photoswitchable unit and diketopiperazine as the binding station was synthesized and studied by NMR and UV/Vis spectroscopy. Glass surfaces have been functionalized with pyridine‐terminated SAMs and subsequently with multilayers of macrocycles through layer‐by‐layer self assembly. A preferred orientation of the macrocycles could be confirmed by NEXAFS spectroscopy. The photocontrolled deposition of the axle into the surface‐bound macrocycle‐multilayers was monitored by UV/Vis spectroscopy and led to an increase of the molecular order, as indicated by more substantial linear dichroism effects in angle‐resolved NEXAFS spectra.     

From NMP to RAFT and Thiol‐Ene Chemistry by In Situ Functionalization of Nitroxide Chain Ends

A straightforward, novel strategy based on the in situ functionalization of polymers prepared by nitroxide‐mediated polymerization (NMP), for the use as an extension toward block copolymers and post‐polymerization modifications, has been investigated. The nitroxide end group is exchanged for a thiocarbonylthio end group by a rapid transfer reaction with bis(thiobenzoyl) disulfide to generate in situ reversible addition–fragmentation chain transfer (RAFT) macroinitiators. Moreover, not only have these macroinitiators been used in chain extension and block copolymerization experiments by the RAFT process but also a thiol‐terminated polymer is synthesized by aminolysis of the RAFT end group and subsequently reacted with dodecyl vinyl ether by thiol‐ene chemistry.     

Unexpectedly Simple Synthesis of Benzazoles by tBuONa‐Catalyzed Direct Aerobic Oxidative Cyclocondensation of o‐Thio/Hydroxy/Aminoanilines with Alcohols under Air

tBuONa‐catalyzed direct aerobic oxidative cyclocondensation reactions of readily available alcohols and o‐thio/hydroxy/aminoanilines under air have been developed and provide an efficient, practical, and green method for the synthesis of benzazoles. Mechanistic studies revealed that o‐substituted anilines promote the initial aerobic alcohol‐oxidation step, which explains the high reactivity and success of this unexpectedly simple and practical cyclocondensation method.     

Surface modification of UV‐cured epoxy resins by click chemistry

A novel method for surface modification of UV‐cured epoxy network was described. Photoinitiated cationic copolymerization of a bisepoxide, namely 3,4‐epoxy cyclohexylmethyl 3,4‐epoxycyclohexanecarboxylate (EEC) with epibromohydrine (EBH) by using a cationic photoinitiator, [4‐(2‐methylpropyl)phenyl]4‐methylphenyl‐iodonium hexafluorophosphate, in propylene carbonate solution was studied. The real‐time Fourier transform infrared spectroscopic, gel content determination and thermal characterization studies revealed that both EEC and EBH monomers take part in the polymerization and epoxy network possessing bromomethyl functional groups was obtained. The bromine functions of the cured product formed on the glass surface were converted to azide functionalities with sodium azide. Independently prepared alkyne functional poly(ethylene glycol) (PEG) was subsequently anchored to azide‐modified epoxy surface by a “click” reaction. Surface modification of the network through incorporation of hydrophilic PEG chain was evidenced by contact angle measurements. © 2010 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 48: 2862–2868, 2010     

Efficient Curing of Vinyl Carbonates by Thiol‐Ene Polymerization

Vinyl carbonates have recently been identified as a suitable alternative to (meth)acrylates, especially due to the low irritancy and cytotoxicity of these monomers. The drawback of some vinyl carbonates containing abstractable hydrogens arises through their moderate reactivity compared with acrylates. Within this paper, we use the thiol‐ene concept to enhance the photoreactivity of vinyl carbonates to a large extent to reach the level of those of similar acrylates. Mechanical properties of the final thiol‐ene polymers were determined by nanoindentation. Furthermore, low toxicity of all components was confirmed by osteoblast cell culture experiments.     

Synthesis and Spatiotemporal Modification of Biocompatible and Stimuli‐Responsive Carboxymethyl Cellulose Hydrogels Using Thiol‐Norbornene Chemistry

Carboxymethyl cellulose (CMC) is functionalized with norbornene groups to undergo thiol‐norbornene cross‐linking reactions. Hydrogels synthesized from a single norbornene‐modified carboxymethyl cellulose (NorCMC) via a light‐initiated thiol‐ene cross‐linking reaction with a variety of dithiol cross‐linkers yield hydrogels with a tunable compression modulus ranging from 1.7 to 103 kPa. Additionally, thermoresponsiveness is spatiotemporally imparted to NorCMC hydrogels by photopatterning a dithiol‐terminated poly(N‐isopropyl acrylamide) cross‐linker, enabling swelling and topological control of the hydrogels as a function of incubation temperature. NorCMC hydrogels are cytocompatible as the viability of encapsulated human mesenchymal stem cells (hMSCs) is greater than 85% after 21 d while using a variety of cross‐linkers. Moreover, hMSCs can remodel, adhere, and spread in the NorCMC matrix cross‐linked with a matrix metalloproteinase‐degradable peptide, further demonstrating the utility of these materials as a tunable biomaterial.     

Polysiloxane‐Based Luminescent Elastomers Prepared by Thiol–ene “Click” Chemistry

Side‐chain vinyl poly(dimethylsiloxane) has been modified with mercaptopropionic acid, methyl 3‐mercaptopropionate, and mercaptosuccinic acid. Coordinative bonding of Eu^III to the functionalized polysiloxanes was then carried out and crosslinked silicone elastomers were prepared by thiol–ene curing reactions of these composites. All these europium complexes could be cast to form transparent, uniform, thin elastomers with good flexibility and thermal stability. The networks were characterized by FTIR, NMR, UV/Vis, and luminescence spectroscopy as well as by scanning electron microscopy, thermogravimetric analysis, and X‐ray photoelectron spectroscopy. The europium elastomer luminophores exhibited intense red light at 617 nm under UV excitation at room temperature due to the ⁵D₀→⁷F₂ transition in Eu^III ions. The newly synthesized luminescent materials offer many advantages, including the desired mechanical flexibility. They cannot be dissolved or fused, and so they have potential for use in optical and electronic applications.     

Photoswitchable Hydrogel Surface Topographies by Polymerisation‐Induced Diffusion

Herein, we describe the preparation of patterned photoresponsive hydrogels by using a facile method. This polymer‐network hydrogel coating consists of N‐isopropylacrylamide (NIPAAM), cross‐linking agent tripropylene glycol diacrylate (TPGDA), and a new photochromic spiropyran monoacrylate. In a pre‐study, a linear NIPAAM copolymer (without TPGDA) that contained the spiropyran dye was synthesised, which showed relatively fast photoswitching behaviour. Subsequently, the photopolymerisation of a similar monomer mixture that included TPGDA afforded freestanding hydrogel polymer networks. The light‐induced isomerisation of protonated merocyanine into neutral spiropyran under slightly acidic conditions resulted in macroscopic changes in the hydrophilicity of the entire polymer film, that is, shrinkage of the hydrogel. The degree of shrinkage could be controlled by changing the chemical composition of the acrylate mixture. After these pre‐studies, a hydrogel film with spatially modulated cross‐link density was fabricated through polymerisation‐induced diffusion, by using a patterned photomask. The resulting smooth patterned hydrogel coating swelled in slightly acidic media and the swelling was higher in the regions with lower cross‐linking densities, thus yielding a corrugated surface. Upon exposure to visible light, the surface topography flattened again, thus showing that a hydrogel coating could be created, the topography of which could be controlled by light irradiation.