Unravelling Competitive Interactions between Polymer Side Chains and End Groups with ß-Cyclodextrin.

This study investigates unexpected competitive host-guest interactions of ß-cyclodextrin (ß-CD), which can occur with polymers in aqueous solution, using the examples of the two polymers poly(oligo(ethylene glycol) methyl ether methacrylate) and poly(glycerol mono methacrylate). Systematic structural modifications of the polymer provide insight into the host-guest interaction with ß-CD and the competition between side chains and end groups such as hydrophobic end groups remaining from reversible addition fragmentation chain transfer polymerization or intentionally implemented molecular recognition units such as arylazopyrazole photoswitches.

Arylazopyrazoles for Conjugation by CuAAC Click Chemistry.

Molecular photoswitches are increasingly being implemented in bioactive compounds and responsive materials. For this purpose, photoswitches must be coupled to a wide variety of substrates and scaffolds. We present a library of "clickable" arylazopyrazoles (AAPs), which can be conjugated by Cu-catalyzed alkyne azide cycloaddition (CuAAC). All synthesized AAP alkynes show good photostationary states (at least 88%) and long half-life times of the Z-isomer (18 to 108 h). The AAP azides decompose upon exposure to ultraviolet (UV) irradiation, but after CuAAC, all AAPs exhibit good photophysical properties.

Stiffness Modulation and Pulsatile Release in Dual Responsive Hydrogels.

Inspired by nature, self-regulation can be introduced in synthetic hydrogels by incorporating chemo-mechanical signals or coupled chemical reactions to maintain or adapt the material's physico-chemical properties when exposed to external triggers. In this work, we present redox and light dual stimuli responsive hydrogels capable of rapidly adapting the polymer crosslinking network while maintaining hydrogel stability. Upon irradiation with UV light, polymer hydrogels containing redox responsive disulfide crosslinks and light responsive ortho-nitrobenzyl moieties show a release of payload accompanied by adaptation of the hydrogel network towards higher stiffness due to in situ crosslinking by S-nitrosylation. Whereas the hydrogel design allows the network to either become softer in presence of reducing agent glutathione or stiffer upon UV irradiation, simultaneous application of both stimuli induces network self-regulation resulting in a pulsatile form of payload release from the hydrogel. Finally, adaptive stiffness was used to make tunable hydrogels as substrates for different cell lines.

Photoswitching of arylazopyrazoles upon S1 (nπ*) excitation studied by transient absorption spectroscopy and ab initio molecular dynamics.

Arylazopyrazoles (AAPs) are an important class of molecular photoswitches with high photostationary states (PSS) and long thermal lifetimes. The ultrafast photoisomerization of four water-soluble arylazopyrazoles, all of them featuring an ortho-dimethylated pyrazole ring, is studied by narrowband femtosecond transient absorption spectroscopy and ab initio molecular dynamics simulations. Upon S1 (nπ*) photoexcitation of the planar E-isomers (E-AAPs), excited-state bi-exponential decays with time constants τ1 in the 220-440 fs range and τ2 in the 1.4-1.8 ps range are observed, comparable to those reported for azobenzene (AB). This is indicative of the same photoisomerization mechanism as has been reported for ABs. In contrast to the planar E-AAPs, a twisted E-AAP with two methyl groups in ortho-position of the phenyl ring displays faster initial photoswitching with τ1 = 170 ± 10 fs and τ2 = 1.6 ± 0.1 ps. Our static DFT calculations and ab initio molecular dynamics simulations of E-AAPs on the S0 and S1 potential energy surfaces suggest that twisted E-isomer azo photoswitches exhibit faster initial photoisomerization dynamics out of the Franck-Condon region due to a weaker π-coordination of the central CNNC unit to the aromatic ligands.

Calamitic Liquid Crystals for Reversible Light-Modulated Phase Regulation Based on Arylazopyrazole Photoswitches.

Invited for the cover of this issue are the groups of Kentaro Tanaka at Nagoya University and Bart Jan Ravoo at the University of Münster. The image depicts the photoisomerization of a mesogen upon irradiation with different wavelengths of light. Read the full text of the article at 10.1002/chem.202302958.

Calamitic Liquid Crystals for Reversible Light-Modulated Phase Regulation Based on Arylazopyrazole Photoswitches.

The design of responsive liquid crystals enables a diversity of technological applications. Especially photochromic liquid crystals gained a lot of interest in recent years due to the excellent spatiotemporal control of their phase transitions. In this work we present calamitic light responsive mesogens based on a library of arylazopyrazole photoswitches. These compounds show liquid-crystalline behavior as shown by differential scanning calorimetry, grazing incidence X-ray diffraction and polarized optical microscopy. UV-vis spectroscopy and NMR analysis confirmed the excellent photophysical properties in solution and thin film. Additionally, polarized optical microscopy studies of the pristine compounds show reversible phase transition upon irradiation with light. Moreover, as a dopant in the commercially available liquid crystal 4-cyano-4'-pentylbiphenyl (5CB), the temperature range was reduced to ambient temperatures while preserving the photophysical properties. Remarkably, this co-assembled system shows reversible liquid-crystalline to isotropic phase transition upon irradiation with light of different wavelengths. The spatiotemporal control of the phase transition of the liquid crystals offers opportunities in the development of optical devices.

Matrix-Enhanced SIMS: The Influence of Primary Ion Species and Cluster Size on Ion Yield and Ion Yield Enhancement of Lipids.

Time-of-flight secondary ion mass spectrometry is one of the most promising techniques for label-free analysis of biomolecules with nanoscale spatial resolution. However, high-resolution imaging of larger biomolecules such as phospholipids and peptides is often hampered by low yields of molecular ions. Matrix-enhanced SIMS (ME-SIMS), in which an organic matrix is added to the sample, is one promising approach to enhancing the ion yield for biomolecules. Optimizing this approach has, however, been challenging because the processes involved in increasing the ion yield in ME-SIMS are not yet fully understood. In this work, the matrix α-cyano-4-hydroxycinnamic acid (HCCA) has been combined with cluster primary ion analysis to better understand the roles of proton donation and reduced fragmentation on lipid molecule ion yield. A model system consisting of 1:100 mol ratio dipalmitoylphosphatidylcholine (DPPC) in HCCA as well as an HCCA-coated mouse brain cryosection have been studied using a range of Bi and Ar cluster ions. Although the molecular ion yield increased with an increase in cluster ion size, the enhancement of the signals from intact lipid molecules decreased with an increase in cluster ion size for both the model system and the mouse brain. Additionally, in both systems, protonated molecular ions were significantly more enhanced than sodium and potassium cationized molecules for all of the primary ions utilized. For the model system, the DPPC molecular ion yield was increased by more than an order of magnitude for all of the primary ions studied, and fragmentation of DPPC was dramatically reduced. However, on the brain sample, even though the HCCA matrix reduced DPPC fragmentation for all of the primary ions studied, the matrix coating suppressed the ion yield for some lipids when the larger cluster primary ions were employed. This indicated insufficient migration of the lipids into the matrix coating, so that dilution by the matrix overpowered the enhancement effect. This study provides strong evidence that the HCCA matrix both enhances protonation and reduces fragmentation. For imaging applications, the ability of the analytes to migrate to the surface of the matrix coating is also a critical factor for useful signal enhancement. This work demonstrates that the HCCA matrix provides a softer desorption environment when using Bi cluster ions than that obtained using the large gas cluster ions studied alone, indicating the potential for improved high spatial resolution imaging with ME-SIMS.

Multi-responsive Electropolymer Surface Coatings Based on Azo Molecular Switches and Carbazoles: Light, pH, and Electrochemical Control of Z→E Isomerization in Thin Films.

Light-responsive surfaces are attracting increasing interest, not least because their physicochemical properties can be selectively and temporally controlled by a non-invasive stimulus. Most existing immobilization strategies involve the chemical attachment of light-responsive moieties to the surface, although this approach often suffers from a low surface concentration of active species or a high inhomogeneity of applied coatings. Herein, electropolymerization of carbazoles as a facile and rapid approach for preparing light-responsive azo-based surface coatings is presented. The electrochemical oxidative polymerization of bis-carbazole containing azo-monomers yields stable films, in which the photochemical properties and specific pH sensitivity of azo molecular switches are retained. Moreover, the molecular design enables electrocatalytic control over Z→E azo double bond isomerization facilitated by the conductive polycarbazole backbone. Ultimately, the high degree of control over macromolecular properties yields conductive surface coatings responsive to a range of stimuli, showing great promise as a strategy for versatile application in organic electronics.

Water-Soluble Arylazoisoxazole Photoswitches.

Azoheteroarenes are emerging as powerful alternatives to azobenzene molecular photoswitches. In this study, water-soluble arylazoisoxazole photoswitches are introduced. UV/vis and NMR spectroscopy revealed moderate to very good photostationary states and reversible photoisomerization between the E- and Z-isomers over multiple cycles with minimal photobleaching. Several arylazoisoxazoles form host-guest complexes with ß- and γ-cyclodextrin with significant differences in binding constants for each photoisomer as shown by isothermal titration calorimetry and NMR experiments, indicating their potential for photoresponsive host-guest chemistry in water. One carboxylic acid functionalized arylazoisoxazole can act as a hydrogelator, allowing gel properties to be manipulated reversibly with light. The hydrogel was characterized by rheological experiments, atom force microscopy and transmission electron microscopy. These results demonstrate that arylazoisoxazoles can find applications as molecular photoswitches in aqueous media.

Selective Removal of Gold: N-Heterocyclic Carbenes as Positive Etch Resists on Planar Gold Surfaces.

N-Heterocyclic carbene (NHC)-modified planar gold surfaces (NHC@Au) were found to be more susceptible toward wet chemical etching than undecorated surface areas. Site-selective decoration of NHCs on Au was achieved by microcontact printing (µCP) of the NHC precursors 1,3-bis(diisopropylphenyl)imidazol-3-ium hydrogen carbonate (IPr(H)[HCO3]) or 1,3-dimethylbenzimidazol-3-ium hydrogen carbonate (BIMe(H)[HCO3]). Strikingly, BIMe@Au showed concentration-dependent etching behavior, tunable from a positive resist to a negative resist. Surface patterning was verified by time-of-flight secondary-ion mass spectrometry and Kelvin probe force microscopy. Moreover, orthogonal µCP enabled the patterned functionalization of planar Au with both IPr and 1-eicosanethiol and the subsequent formation of three-dimensional structures with a single etching step. The selective removal of Au by functionalization with a surface ligand is unprecedented and enables novel applications of NHCs in materials chemistry and nanofabrication.

Rapid and reversible optical switching of cell membrane area by an amphiphilic azobenzene.

Cellular membrane area is a key parameter for any living cell that is tightly regulated to avoid membrane damage. Changes in area-to-volume ratio are known to be critical for cell shape, but are mostly investigated by changing the cell volume via osmotic shocks. In turn, many important questions relating to cellular shape, membrane tension homeostasis and local membrane area cannot be easily addressed because experimental tools for controlled modulation of cell membrane area are lacking. Here we show that photoswitching an amphiphilic azobenzene can trigger its intercalation into the plasma membrane of various mammalian cells ranging from erythrocytes to myoblasts and cancer cells. The photoisomerization leads to a rapid (250-500 ms) and highly reversible membrane area change (ca 2 % for erythrocytes) that triggers a dramatic shape modulation of living cells.

Azoheteroarene and Diazocine Molecular Photoswitches: Self-Assembly, Responsive Materials and Photopharmacology.

Aromatic units tethered with an azo (-N=N-) functionality comprise a unique class of compounds, known as molecular photoswitches, exhibiting a reversible transformation between their E- and Z-isomers in response to photo-irradiation. Photoswitches have been explored extensively in the recent past to prepare dynamic self-assembled materials, optoelectronic devices, responsive biomaterials, and more. Most of such materials involve azobenzenes as the molecular photoswitch and to date, SciFinder lists more than 7000 articles and 1000 patents. Subsequently, a great deal of effort has been invested to improve the photo-isomerization efficiency and related mesoscopic properties of azobenzenes. Recently, azoheteroarenes and cyclic azobenzenes, such as arylazopyrazoles, arylazoisoxazoles, arylazopyridines, and diazocines, have emerged as second generation molecular photoswitches beyond conventional azobenzenes. These photoswitches offer distinct photoswitching behavior and responsive properties which make them highly promising candidates for multifaceted applications ranging from photoresponsive materials to photopharmacophores. In this minireview, we introduce the structural refinement and photoresponsive properties of azoheteroarenes and diazocines and summarize the state-of-the-art on utilizing these photoswitches as responsive building blocks in supramolecular assembly, material science and photopharmacology, highlighting their versatile photochemical behavior, enhanced functionality, and latest applications.

Arylazopyrazole-Modified Thiolactone Acrylate Copolymer Brushes for Tuneable and Photoresponsive Wettability of Glass Surfaces.

Photoswitches have long been employed in coatings for surfaces and substrates to harness light as a versatile stimulus to induce responsive behavior. We previously demonstrated the viability of arylazopyrazole (AAP) as a photoswitch in self-assembled monolayers (SAMs) on silicon and glass surfaces for photoresponsive wetting applications. We now aim to transfer the excellent photophysical properties of AAPs to polymer brush coatings. Compared to SAMs, polymer brushes offer enhanced stability and an increase of the thickness and density of the functional organic layer. In this work, we present thiolactone acrylate copolymer brushes which can be post-modified with AAP amines as well as hydrophobic acrylates, making use of the unique chemistry of the thiolactones. This strategy enables photoresponsive wetting with a tuneable range of contact angle change on glass substrates. We show the successful synthesis of thiolactone hydroxyethyl acrylate copolymer brushes by means of surface-initiated atom-transfer radical polymerization with the option to either prepare homogeneous brushes or to prepare micrometer-sized brush patterns by microcontact printing. The polymer brushes were analyzed by atomic force microscopy, time-of-flight secondary ion spectrometry, and X-ray photoelectron spectroscopy. Photoresponsive behavior imparted to the brushes by means of post-modification with AAP is monitored by UV/vis spectroscopy, and wetting behavior of homogeneous brushes is measured by static and dynamic contact angle measurements. The brushes show an average change in static contact angle of around 13° between E and Z isomer of the AAP photoswitch for at least five cycles, while the range of contact angle change can be fine-tuned between 53.5°/66.5° (E/Z) and 81.5°/94.8° (E/Z) by post-modification with hydrophobic acrylates.

Light-Responsive Conductive Surface Coatings on the Basis of Azidomethyl-PEDOT Electropolymer Films.

The design of responsive coatings has gained increasing attention recently, with light-responsive interfaces receiving particular appreciation, as their surface properties can be modulated with excellent spatiotemporal control. In this article, we present light-responsive conductive coatings acquired through a copper(I)-catalyzed azide-alkyne cycloaddition (CuAAC) reaction between electropolymerized azide-functionalized poly(3,4-ethylenedioxythiophene) (PEDOT-N3) and arylazopyrazole (AAP)-bearing alkynes. The UV/vis and X-ray photoelectron spectroscopy (XPS) data indicate a successful post-modification, supporting a covalent attachment of AAP moieties to PEDOT-N3. The thickness and degree of PEDOT-N3 modification are accessible by varying the amount of passed charge during electropolymerization and time of reaction, respectively, providing a degree of synthetic control over the physicochemical material properties. The produced substrates demonstrate a reversible and stable light-driven switching of photochromic properties in both "dry" and swelled states, as well as efficient electrocatalytic Z → E switching. The AAP-modified polymer substrates exhibit a light-controlled wetting behavior, demonstrating a consistently reversible switching of the static water contact angle with a difference up to 10.0° for CF3-AAP@PEDOT-N3. The results highlight the application of conducting PEDOT-N3 for the covalent immobilization of molecular switches while preserving their stimuli-responsive features.

Patterning of Hydrophilic and Hydrophobic Gold and Magnetite Nanoparticles by Dip Pen Nanolithography.

Nanoparticles offer unique physical and chemical properties. Dip pen nanolithography of nanoparticles enables versatile patterning and nanofabrication with potential application in electronics and sensing, but is not well studied yet. Herein, the patterned deposition of various nanoparticles onto unmodified silicon substrates is presented. It is shown that aqueous solutions of hydrophilic citrate and cyclodextrin functionalized gold nanoparticles as well as poly(acrylic) acid decorated magnetite nanoparticles are feasible for writing nanostructures. Both smaller and larger nanoparticles can be patterned. Hydrophobic oleylamine or n-dodecylamine capped gold nanoparticles and oleic acid decorated magnetite nanoparticles are deposited from toluene. Tip loading is carried out by dip-coating, and writing succeeds fast within 0.1 s. Also, coating with longer tip dwell times, at different relative humidity and varying frequency are studied for deposition of nanoparticle clusters. The resulting feature size is between 300 and 1780 nm as determined by scanning electron microscopy. Atomic force microscopy confirms that the heights of the deposited structures correspond to a single or double layer of nanoparticles. Higher writing speeds lead to smaller line thicknesses, offering possibilities to more complex structures. Dip pen nanolithography can hence be used to pattern nanoparticles on silicon substrates independent of the surface chemistry.

Influence of Matrix pKa on Molecular Ion Formation in Matrix-Enhanced Secondary-Ion Mass Spectrometry.

Time-of-flight secondary ion mass spectrometry (ToF-SIMS) is one of the most important techniques for chemical imaging of nanomaterials and biological samples with high lateral resolution. However, low ionization efficiency limits the detection of many molecules at low concentrations or in very small volumes. One promising approach to increasing the sensitivity of the technique is by the addition of a matrix that promotes ionization and desorption of important analyte molecules. This approach is known as matrix-enhanced secondary-ion mass spectrometry (ME-SIMS). We have investigated the effect of matrix acidity on molecular ion formation in three different biomolecules. A series of cinnamic acid based matrixes that vary in acidity was employed to systematically investigate the influence of matrix acidity on analyte ion formation. The positive ion signal for all three biomolecules showed a strong increase for more acidic matrixes. The most acidic matrix was then vapor-deposited onto mouse brain sections. This led to significant enhancement of lipid signals from the brain. This work indicates that proton donation plays an important role in the formation of molecular ions in ME-SIMS.

Versatile Surface Patterning with Low Molecular Weight Photoswitches.

Surface patterning of functional materials is a key technology in various fields such as microelectronics, optics, and photonics. In micro- and nanofabrication, polymers are frequently employed either as photoreactive or thermoresponsive resists that enable further fabrication steps, or as functional adlayers in electronic and optical devices. In this article, a method is presented for imprint lithography using low molecular weight arylazoisoxazoles photoswitches instead of polymer resists. These photoswitches exhibit a rapid and reversible solid-to-liquid phase transition upon photo-isomerization at room temperature, making them highly suitable for reversible surface functionalization at ambient conditions. Beyond photo-induced imprint lithography with multiple write-and-erase cycles, prospective applications as patterned matrix for nanoparticles and etch resist on gold surfaces are demonstrated.

Reversible, Red-Shifted Photoisomerization in Protonated Azobenzenes.

Azobenzenes are among the best-studied molecular photoswitches and play a key role in the search for red-shifted photoresponsive materials for extended applications. Currently, most approaches deal with aromatic substitution patterns to achieve visible light application, on occasion paired with protonation to yield red-shifted absorption of the azonium species. Appropriate substitution patterns are essential to stabilize the latter approach, as conventional acids are known to induce a fast Z- to E-conversion. Here, we show that steady-state protonation of the azo-bridge instead is possible in simple azobenzenes when the pKa of the acid is low enough, yielding both the Z- and E-azonium as supported by UV-vis- and 1H NMR spectroscopy as well as density functional theory calculations. Moreover, the steady-state protonation of para-methoxyazobenzene, specifically, yields photoisomerizable azonium ions in which the direction of switching is essentially reversed, that is, visible light produces the out-of-equilibrium Z-azonium. Although the current conditions render the visible light photoswitch unsuitable for in vivo and material application, the demonstrated understanding of simple azobenzenes paves the way for a great range of further work on this already widely studied photoswitch.

Reversible Photoresponsive Modulation of Osmotic Pressure via Macromolecular Host-Guest Interaction.

The high spatiotemporal resolution of light as an external stimulus allows the control of shape, mechanical properties, and even forces generated by photoresponsive soft materials. For this purpose, supramolecular systems that respond readily and reversibly to photoirradiation and convert microscopic changes into macroscopic effects are needed. This work demonstrates the reversible light-responsive modulation of the osmotic pressure of an aqueous solution of an azobenzene-containing polymer (azopolymer) and α-cyclodextrin. Osmometry shows that this multivalent and photoresponsive host-guest complex can be used to modulate the concentration of solutes in the solution. Upon alternating irradiation with UV and blue light, the osmolality is reversibly switched by 28 mOsm kg-1. The switching amplitude increases linearly with the concentration of azopolymer and cyclodextrin. This drastic change in osmotic pressure is achieved by carefully designing an azopolymer that provides multivalent interactions as well as high water solubility. In this way, our study demonstrates a tunable control of colligative properties by photoinduced modulation of supramolecular interactions.

Mediating Oxidation of Thioethers with Iodine-A Mild and Versatile Pathway to Trigger the Formation of Peptide Hydrogels.

The development of redox-triggerable peptide hydrogels poses fundamental challenges, since the highly specific peptide architectures required inevitably limit the versatility of such materials. A powerful, yet rarely applied approach to bypass those barriers is the application of a mediating redox reaction to gradually decrease the pH during hydrogel formation. We report a versatile strategy to trigger the formation of peptide hydrogels from readily accessible acid-triggerable gelators by generating protons by oxidation of thioethers with triiodide. Adding thiodiglycol as a readily available thioether auxiliary to the basic precursor solution of a peptide gelator efficiently yielded hydrogels after mixing with triiodide, as studied in detail for Nap-FF and demonstrated for other peptides. Furthermore, incorporation of the thioether moiety in the gelator backbone via the amino acid methionine, as shown for the tailormade Nap-FMDM peptide, reduces the number of required additives.