Accessing a Diverse Set of Functional Red-Light Photoswitches by Selective Copper-Catalyzed Indigo N-Arylation.

The ability to correlate the structure of a molecule with its properties is the key to the rational and accelerated design of new functional compounds and materials. Taking photoswitches as an example, the thermal stability of the metastable state is a crucial property that dictates their application in molecular systems. Indigos have recently emerged as an attractive motif for designing photoswitchable molecules due to their red-light addressability, which can be advantageous in biomedical and material applications. The lack of synthetic techniques to derivatize the abundant parent dye and a thorough understanding of the impact of structural factors on the photochemical and thermal properties hinder broad applications of this emerging photoswitch class. Herein, we report an efficient copper-catalyzed indigo N-arylation that enables the installation of a wide variety of aryl moieties carrying useful functional groups. The exclusive selectivity for monoarylation likely originates from a bimetallic cooperative mechanism through a binuclear copper-indigo intermediate. Functional N-aryl-N'-alkylindigos were prepared and shown to photoisomerize efficiently under red light. Moreover, this design allows for the modulation of thermal half-lives through N-aryl substituents, while the N'-alkyl groups enable the independent attachment of functional moieties without affecting the photochromic properties. A strong correlation between the structure of the N-aryl moiety and the thermal stability of the photogenerated Z-isomers was achieved by multivariate linear regression models obtained through a data-science workflow. This work thus builds an avenue leading to versatile red-light photoswitches and a general method for structure-property correlation that is expected to be broadly applicable to the design of photoresponsive molecules.

Multifold Post-Modification of Macrocycles and Cages by Isocyanate-Induced Azadefluorination Cyclisation.

We present the multiple post-modification of organic macrocycles and cages, introducing functional groups into two- and three-dimensional supramolecular scaffolds bearing fluorine substituents, which opens up new possibilities in multi-step supramolecular chemistry employing the vast chemical space of readily available isocyanates. The mechanism and scope of the reaction that proceeds after isocyanate addition to the benzylamine motif via an azadefluorination cyclisation (ADFC) were investigated using DFT calculations, and a series of aromatic isocyanates with different electronic properties were tested. The compounds show excellent chemical stability and were fully characterised. They can be used for subsequent cross-coupling reactions, and ADFC can be used directly to generate cross-linked membranes from macrocycles or cages when using ditopic isocyanates. Single-crystal X-ray (SC-XRD) analysis shows the proof of the formation of the desired supramolecular entity together with the connectivity predicted by calculations and from 19F NMR shifts, allowing the late-stage functionalisation of self-assembled macrocycles and cages by ADFC.

Photoresponsive Supramolecular Cages and Macrocycles.

The utilisation of light to achieve precise manipulation and control over the structure and function of supramolecular assemblies has emerged as a highly promising approach in the development of complex, configurable, or multifunctional systems and nanoscopic machine-like entities. In this minireview, we highlight recent examples of self-assembled and covalently bound cages and macrocycles with a focus on the external and internal functionalisation of a structure with a photoswitchable unit or the embedment of a photoswitch into the framework of a structure. Functionalising the interior or exterior of a supramolecular cage or macrocycle with a photoresponsive group enables control over different properties, such as guest binding or assembly in the solid-state, while the overall shape of the assembly often undergoes no significant change. By directly integrating a photoswitchable unit into the framework of a supramolecular structure, the isomerisation can either induce a geometry change, the disassembly, or the disassembly and reassembly of the structure. Historical and recent examples covered in this review are based on azobenzene, diarylethene, stilbene photoswitches, or alkene motors that were incorporated into macrocycles and cages constructed by metal-organic, dynamic covalent, or covalent bonds.

Mechanoresponsive Metal-Organic Cage-Crosslinked Polymer Hydrogels.

We report the formation of metal-organic cage-crosslinked polymer hydrogels. To enable crosslinking of the cages and subsequent network formation, we used homodifunctionalized poly(ethylene glycol) (PEG) chains terminally substituted with bipyridines as ligands for the Pd6 L4 corners. The encapsulation of guest molecules into supramolecular self-assembled metal-organic cage-crosslinked hydrogels, as well as ultrasound-induced disassembly of the cages with release of their cargo, is presented in addition to their characterization by nuclear magnetic resonance (NMR) techniques, rheology, and comprehensive small-angle X-ray scattering (SAXS) experiments. The constrained geometries simulating external force (CoGEF) method and barriers using a force-modified potential energy surface (FMPES) suggest that the cage-opening mechanism starts with the dissociation of one pyridine ligand at around 0.5 nN. We show the efficient sonochemical activation of the hydrogels HG3 -6 , increasing the non-covalent guest-loading of completely unmodified drugs available for release by a factor of ten in comparison to non-crosslinked, star-shaped assemblies in solution.

Photoresponsive Dissipative Macrocycles Using Visible-Light-Switchable Azobenzenes.

Visible light can be used to shift dynamic covalent imine assemblies out of equilibrium. We studied a fluorinated azobenzene building block that reliably undergoes geometric isomerism upon irradiation. The building block was used in combination with two different amines, ethylenediamine and R,R-1,2-diaminocyclohexane, to create a library of imine macrocycles. Whereas the simple amine can be used to access a polymeric state and a defined bowl-shaped macrocycle, the chiral amine gives access to a rich network of macrocycles that undergo both isomerisation as well as interconversion between different macrocyclic species, thereby allowing for control over the number of monomers involved in the cyclo-oligomerization; 1 H- and 19 F-DOSY NMR, MALDI-MS measurements, and UV/Vis spectroscopy were used to study the processes.

Synthesis and Characterization of a Crystalline Imine-Based Covalent Organic Framework with Triazine Node and Biphenyl Linker and Its Fluorinated Derivate for CO2/CH4 Separation.

A catalyst-free Schiff base reaction was applied to synthesize two imine-linked covalent organic frameworks (COFs). The condensation reaction of 1,3,5-tris-(4-aminophenyl)triazine (TAPT) with 4,4'-biphenyldicarboxaldehyde led to the structure of HHU-COF-1 (HHU = Heinrich-Heine University). The fluorinated analog HHU-COF-2 was obtained with 2,2',3,3',5,5',6,6'-octafluoro-4,4'-biphenyldicarboxaldehyde. Solid-state NMR, infrared spectroscopy, X-ray photoelectron spectroscopy, and elemental analysis confirmed the successful formation of the two network structures. The crystalline materials are characterized by high Brunauer-Emmett-Teller surface areas of 2352 m2/g for HHU-COF-1 and 1356 m2/g for HHU-COF-2. The products of a larger-scale synthesis were applied to prepare mixed-matrix membranes (MMMs) with the polymer Matrimid. CO2/CH4 permeation tests revealed a moderate increase in CO2 permeability at constant selectivity for HHU-COF-1 as a dispersed phase, whereas application of the fluorinated COF led to a CO2/CH4 selectivity increase from 42 for the pure Matrimid membrane to 51 for 8 wt% of HHU-COF-2 and a permeability increase from 6.8 to 13.0 Barrer for the 24 wt% MMM.

Fast, solvent-free synthesis of ferrocene-containing organic cages via dynamic covalent chemistry in the solid state.

A simple, solvent-free synthetic protocol towards the synthesis of organic self-assembled macromolecules has been established. By employing mechanochemistry using glassware readily available to every organic chemist, we were able to synthesise three novel organic cage compounds exemplarily and to speed up the synthesis of a ferrocene-containing macrocycle by a factor of 288 compared to the solution-based synthesis. The structural investigation of the newly synthesised cages revealed different modes of connectivity from using ferrocene-containing aldehydes caused by the free rotation of the cyclopentadienyl units against each other. By extending the facile solvent-free synthesis to ball-milling, even compounds that show lower reactivity could be employed in the dynamic covalent formation of organometallic cage compounds. The presented protocol gives access to otherwise inaccessible structures, speeds up general synthetic workflows, and simultaneously reduces the environmental impact of supramolecular syntheses.

Supramolecular networks by imine halogen bonding.

Halogen bonding of neutral donors using imine groups of porous organic cage compounds as acceptors leads to the formation of halogen-bonded frameworks. We report the use of two different imine cages, in combination with three electron-poor halogen bond donors. Four resulting solid-state structures elucidated by single-crystal X-ray analysis are presented and analysed for the first time by plane-wave DFT calculations and QTAIM-analyses of the entire unit cells, demonstrating the formation of halogen bonds within the networks. The supramolecular frameworks can be obtained either from solution or mechanochemically by liquid-assisted grinding.

Release of Molecular Cargo from Polymer Systems by Mechanochemistry.

The design and manipulation of (multi)functional materials at the nanoscale holds the promise of fuelling tomorrow's major technological advances. In the realm of macromolecular nanosystems, the incorporation of force-responsive groups, so called mechanophores, has resulted in unprecedented access to responsive behaviours and enabled sophisticated functions of the resulting structures and advanced materials. Among the diverse force-activated motifs, the on-demand release or activation of compounds, such as catalysts, drugs, or monomers for self-healing, are sought-after since they enable triggering pristine small molecule function from macromolecular frameworks. Here, we highlight examples of molecular cargo release systems from polymer-based architectures in solution by means of sonochemical activation by ultrasound (ultrasound-induced mechanochemistry). Important design concepts of these advanced materials are discussed, as well as their syntheses and applications.

Supramolecular Alloys from Fluorinated Hybrid Tri4 Di6 Imine Cages.

To create innovative materials, efficient control and engineering of pore sizes and their characteristics, crystallinity and stability is required. Eight hybrid Tri4 Di6 imine cages with a tunable degree of fluorination and one fully fluorinated Tri4 Di6 imine cage are investigated. Although the fluorinated and the non-fluorinated building blocks used herein differ vastly in reactivity, it was possible to gain control over the outcome of the self-assembly process, by carefully controlling the feed ratio. This represents the first hybrid material based on fluorinated/hydrogenated porous organic cages (POCs). These cages with unlimited miscibility in the solid state were obtained as highly crystalline samples after recrystallization and even showed retention of the crystal lattice, forming alloys. All mixtures and the fully fluorinated Tri4 Di6 imine cage were analyzed by MALDI-MS, single-crystal XRD, powder XRD and in regard to thermal stability (TGA).

Mechanochemical Release of Non-Covalently Bound Guests from a Polymer-Decorated Supramolecular Cage.

Supramolecular coordination cages show a wide range of useful properties including, but not limited to, complex molecular machine-like operations, confined space catalysis, and rich host-guest chemistries. Here we report the uptake and release of non-covalently encapsulated, pharmaceutically-active cargo from an octahedral Pd cage bearing polymer chains on each vertex. Six poly(ethylene glycol)-decorated bipyridine ligands are used to assemble an octahedral PdII6 (TPT)4 cage. The supramolecular container encapsulates progesterone and ibuprofen within its hydrophobic nanocavity and is activated by shear force produced by ultrasonication in aqueous solution entailing complete cargo release upon rupture, as shown by NMR and GPC analyses.

A porous fluorinated organic [4+4] imine cage showing CO2 and H2 adsorption.

We present the synthesis of a porous, organic [4+4] imine cage containing perfluorinated aromatic panels. Gas adsorption experiments show an uptake of 19.0 wt% CO2 (4.2 mmol g-1, 273 K and at 1 bar) and 1.5 wt% H2 (7.5 mmol g-1, 77 K and at 1 bar) for the specific surface area of 536 m2 g-1 of the crystalline material obtained directly from the reaction mixture, combined with an outstanding thermal stability, making it a very interesting porous material suitable for gas adsorption.

Fluorinated azobenzenes as supramolecular halogen-bonding building blocks.

ortho-Fluoroazobenzenes are a remarkable example of bistable photoswitches, addressable by visible light. Symmetrical, highly fluorinated azobenzenes bearing an iodine substituent in para-position were shown to be suitable supramolecular building blocks both in solution and in the solid state in combination with neutral halogen bonding acceptors, such as lutidines. Therefore, we investigate the photochemistry of a series of azobenzene photoswitches. Upon introduction of iodoethynyl groups, the halogen bonding donor properties are significantly strengthened in solution. However, the bathochromic shift of the π→π* band leads to a partial overlap with the n→π* band, making it slightly more difficult to address. The introduction of iodine substituents is furthermore accompanied with a diminishing thermal half-life. A series of three azobenzenes with different halogen bonding donor properties are discussed in relation to their changing photophysical properties, rationalized by DFT calculations.

[2+2] Halogen-bonded boxes employing azobenzenes.

Herein, we report the synthesis and crystal structures of three [2+2] supramolecular boxes assembled by halogen bonding. The discrete, two-dimensional boxes with a length of 25-30 Å are based on rigid u-shaped halogen acceptors paired with highly fluorinated, azobenzenes bearing halogen bond donors.

Optically switchable organic light-emitting transistors.

Organic light-emitting transistors are pivotal components for emerging opto- and nanoelectronics applications, such as logic circuitries and smart displays. Within this technology sector, the integration of multiple functionalities in a single electronic device remains the key challenge. Here we show optically switchable organic light-emitting transistors fabricated through a judicious combination of light-emitting semiconductors and photochromic molecules. Irradiation of the solution-processed films at selected wavelengths enables the efficient and reversible tuning of charge transport and electroluminescence simultaneously, with a high degree of modulation (on/off ratios up to 500) in the three primary colours. Different emitting patterns can be written and erased through a non-invasive and mask-free process, on a length scale of a few micrometres in a single device, thereby rendering this technology potentially promising for optically gated highly integrated full-colour displays and active optical memory.

Microcrystal Electron Diffraction (MicroED) for Small-Molecule Structure Determination.

The development of new methods to analyze and determine molecular structures parallels the ability to accelerate synthetic research. For many decades, single-crystal analysis by X-ray diffraction (SXRD) has been the definitive tool for structural analysis at the atomic level; the drawback, however, is that a suitable single crystal of the analyte needs to be grown. The recent innovation of the crystalline sponge (CS) method allows the microanalysis of compounds simply soaked in a readily prepared CS crystal, thus circumventing the need to screen crystallization conditions while also using only a trace amount of the sample. In this context, electron diffraction for the structure determination of small molecules is discussed as potentially the next big development in this field.

Efficient Light-Induced pKa †Modulation Coupled to Base-Catalyzed Photochromism.

Photoswitchable acid-base pairs, whose pKa values can be reversibly altered, are attractive molecular tools to control chemical and biological processes with light. A significant, light-induced pKa change of three units in aqueous medium has been realized for two thermally stable states, which can be interconverted using UV and green light. The light-induced pKa modulation is based on incorporating a 3-H-thiazol-2-one moiety into the framework of a diarylethene photoswitch, which loses the heteroaromatic stabilization of the negatively charged conjugate base upon photochemical ring closure, and hence becomes significantly less acidic. In addition, the efficiency of the photoreactions is drastically increased in the deprotonated state, giving rise to catalytically enhanced photochromism. It appears that protonation has a significant influence on the shape of the ground- and excited-state potential energy surfaces, as indicated by quantum-chemical calculations.

N,N'-Disubstituted Indigos as Readily Available Red-Light Photoswitches with Tunable Thermal Half-Lives.

Some rare indigo derivatives have been known for a long time to be photochromic upon irradiation with red light, which should be advantageous for many applications. However, the absence of strategies to tune their thermal half-lives by modular molecular design as well as the lack of proper synthetic methods to prepare a variety of such molecules from the parent indigo dye have so far precluded their use. In this work, several synthetic protocols for N-functionalization have been developed, and a variety of N-alkyl and N-aryl indigo derivatives have been prepared. By installation of electron-withdrawing substituents on the N-aryl moieties, the thermal stability of the Z-isomers could be enhanced while maintaining the advantageous photoswitching properties upon irradiation with red light (660 nm LED). Both experimental data and computational results suggest that the ability to tune thermal stability without affecting the dyes' absorption maxima originates from the twisted geometry of the N-aryl groups. The new indigo photoswitches reported are expected to have a large impact on the development of optical methods and applications in both life and material sciences.

Click Chemistry Derived Pyridazines: Electron-Deficient Building Blocks with Defined Conformation and Packing Structure.

A series of 3,6-bis(4-triazolyl)pyridazines equipped with terminal phenyl substituents with varying degree of fluorination were synthesized by using the facile copper-catalyzed azide-alkyne cycloaddition and their structures were thoroughly investigated in the gas phase, in solution, and in the solid state by employing DFT calculations, NMR spectroscopy, and single-crystal X-ray diffraction, respectively. On the molecular level, their structure is governed by the strong preference of the triazole-pyridazine linkages for the anti-conformation. The supramolecular organization of the molecules in the crystalline solid is controlled by π-stacking, C-H⋅⋅⋅π as well as C-F⋅⋅⋅H interactions. The latter can conveniently be tuned by the number and position of fluorine substituents in the terminal phenyl units, giving rise to either herringbone-like, 1D or 2D lamellar packing. Electrochemistry and optical spectroscopy of all compounds suggest that they might find use as electron-transporting/hole-blocking materials in organic electronics.

Compressed Corannulene in a Molecular Cage.

Self-assembled coordination cages can be employed as a molecular press, where the bowl-shaped guest corannulene (C20H10) is significantly flattened upon inclusion within the hydrophobic cavity. This is demonstrated by the pairwise inclusion of corannulene with naphthalene diimide as well as by the dimer inclusion of bromocorannulene inside the box-like host. The compressed corannulene structures are unambiguously revealed by single-crystal X-ray analysis.