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.

Functional Linkers Support Targeting of Multivalent Tweezers to Taspase1.

Taspase 1 is a unique protease not only pivotal for embryonic development but also implicated in leukemias and solid tumors. As such, this enzyme is a promising while still challenging therapeutic target, and with its protein structure featuring a flexible loop preceding the active site a versatile model system for drug development. Supramolecular ligands provide a promising complementary approach to traditional small-molecule inhibitors. Recently, the multivalent arrangement of molecular tweezers allowed the successful targeting of Taspase 1's surface loop. With this study we now want to take the next logic step und utilize functional linker systems that not only allow the implementation of novel properties but also engage in protein surface binding. Consequently, we chose two different linker types differing from the original divalent assembly: a backbone with aggregation-induced emission (AIE) properties to enable monitoring of binding and a calix[4]arene scaffold initially pre-positioning the supramolecular binding units. With a series of four AIE-equipped ligands with stepwise increased valency we demonstrated that the functionalized AIE linkers approach ligand binding affinities in the nanomolar range and allow efficient proteolytic inhibition of Taspase 1. Moreover, implementation of the calix[4]arene backbone further enhanced the ligands' inhibitory potential, pointing to a specific linker contribution.

Multi-Stimuli-Responsive Water-Dispersible Magnetite Nanoparticles Using Arylazopyrazole-Modified Polymer Ligands.

In order to design new nanomaterials with improved functionalities, magnetite nanoparticles (MNP) modified with arylazopyrazole (AAP) molecular photoswitches are presented. Water dispersibility is achieved by using poly(acrylic acid) (pAA) as a multidentate ligand, which is modified with AAP by amide coupling. The polymer ligand stabilizes the MNP, allows for E-Z isomerization of the photoswitch, and provides pH responsiveness. Three different AAP are synthesized and attached to pAA via amide coupling giving pAA-AAP with photoswitches substituted statistically along the hydrophilic polymer backbone. MNP are synthesized by coprecipitation and pAA-AAP is introduced as a stabilizing agent in situ. Photoisomerization of pAA-AAP and pAA-AAP@MNP is investigated showing good photostationary states and cyclability. The MNP can be assembled and dispersed reversibly in water either by applying a magnetic field or by a change in pH.

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.

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.

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.

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.

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.

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.

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.

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.

Denoising of Mass Spectrometry Images via Inverse Maximum Signal Factors Analysis.

Improving signal-to-noise and, thereby, image contrast is one of the key challenges needed to expand the useful applications of mass spectrometry imaging (MSI). Both instrumental and data analysis approaches are of importance. Univariate denoising techniques have been used to improve contrast in MSI images with varying levels of success. Additionally, various multivariate analysis (MVA) methods have proven to be effective for improving image contrast. However, the distribution of important but low intensity ions can be obscured in the MVA analysis, leading to a loss of chemically specific information. In this work we propose inverse maximum signal factors (MSF) denoising as an alternative approach to both denoising and multivariate analysis for MSI imaging. This approach differs from the standard MVA techniques in that the output is denoised images for each original mass peak rather than the frequently difficult to interpret scores and loadings. Five tests have been developed to optimize and validate the resulting denoised images. The algorithm has been tested on a range of simulated data with different levels of noise, correlated noise, varying numbers of underlying components, and nonlinear effects. In the simulations, an excellent correlation between the true images and the denoised images was observed for peaks with an original signal-to-noise ratio as low as 0.1, as long as there was sufficient intensity in the sum of the selected peaks. The power of the approach was then demonstrated on two time-of-flight secondary ion mass spectrometry (ToF-SIMS) images that contained largely uncorrelated noise and a laser post-ionization matrix-assisted laser desorption/ionization mass spectrometry (MALDI-2-MS) image that contained strongly correlated noise. The improvements in signal-to-noise increased with decreasing intensity of the original peaks. A signal-to-noise improvement of as much as two orders of magnitude was achieved for very low intensity peaks. MSF denoising is a powerful addition to the suite of image processing techniques available for studying mass spectrometry images.

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.

Self-Assembled Monolayers of Arylazopyrazoles on Glass and Silicon Oxide: Photoisomerization and Photoresponsive Wettability.

Surface coatings that respond to external influences and change their physical properties upon application of external stimuli are of great interest, with light being a particularly desirable choice. Photoswitches such as azobenzenes have been employed in a range of photoresponsive coatings. One striking change in physical property of many photoresponsive coatings is their responsive wettability upon illumination. In this work, we present photoswitchable self-assembled monolayers based on arylazopyrazoles (AAPs). In solution, AAPs offer significant improvements in terms of the photostationary state, thermal stability, and fatigue resistance. The AAP photoswitch is coupled to triethoxysilanes for an easy, one-step functionalization of glass and silicon oxide surfaces. We show the synthesis of AAP-based silanes and the successful surface functionalization, and we confirm the excellent photoswitchability of the AAPs in a self-assembled monolayer upon alternating irradiation with UV (365 nm) and green (520 nm) light. The self-assembled monolayers are investigated by UV/vis spectroscopy, X-ray photoelectron spectroscopy (XPS), time-of-flight secondary ion mass spectrometry (ToF-SIMS), and contact angle goniometry. We furthermore investigate the effect of substitution of the AAPs on the photoresponsive wetting behavior and compare this with density functional theory (DFT) calculations of the dipole moments of the AAPs.

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.

Principles and applications of cyclodextrin liquid crystals.

Cyclodextrin-based liquid crystals and their emerging applications are described in this tutorial review, which covers reports from the last decade with a focus on recent developments. Although cyclodextrins are among the best studied macrocyclic host molecules and liquid crystals have found widespread technological application, the integration of cyclodextrins in liquid crystals as versatile supramolecular materials has been barely explored. However, in the last few years promising innovations in molecular design as well as proof-of-concept applications such as ion-conductive and proton-conductive liquid crystals, nanoparticle additives for liquid crystal display technology, polyrotaxane-based liquid crystals and liquid crystal-based sensors have been reported. We discuss various examples of cyclodextrin-based liquid crystals that demonstrate the significant potential of these unique soft materials for future research and interdisciplinary applications.

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.

Self-Assembled Cationic Polypeptide Supramolecular Nanogels for Intracellular DNA Delivery.

Supramolecular nanogels are an emerging class of polymer nanocarriers for intracellular delivery, due to their straightforward preparation, biocompatibility, and capability to spontaneously encapsulate biologically active components such as DNA. A completely biodegradable three-component cationic supramolecular nanogel was designed exploiting the multivalent host-guest interaction of cyclodextrin and adamantane attached to a polypeptide backbone. While cyclodextrin was conjugated to linear poly-L-lysine, adamantane was grafted to linear as well as star shaped poly-L-lysine. Size control of nanogels was obtained with the increase in the length of the host and guest polymer. Moreover, smaller nanogels were obtained using the star shaped polymers because of the compact nature of star polymers compared to linear polymers. Nanogels were loaded with anionic model cargoes, pyranine and carboxyfluorescein, and their enzyme responsive release was studied using protease trypsin. Confocal microscopy revealed successful transfection of mammalian HeLa cells and intracellular release of pyranine and plasmid DNA, as quantified using a luciferase assay, showing that supramolecular polypeptide nanogels have significant potential in gene therapy applications.