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.

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.

Xanthate-supported photo-iniferter (XPI)-RAFT polymerization: facile and rapid access to complex macromolecules.

Xanthate-supported photo-iniferter (XPI)-reversible addition-fragmentation chain-transfer (RAFT) polymerization is introduced as a fast and versatile photo-polymerization strategy. Small amounts of xanthate are added to conventional RAFT polymerizations to act as a photo-iniferter under light irradiation. Radical exchange is facilitated by the main CTA ensuring control over the molecular weight distribution, while xanthate enables an efficient photo-(re)activation. The photo-active moiety is thus introduced into the polymer as an end group, which makes chain extension of the produced polymers possible directly by irradiation. This is in sharp contrast to conventional photo-initiators, or photo electron transfer (PET)-RAFT polymerizations, where radical generation depends on the added small molecules. In contrast to regular photo-iniferter-RAFT polymerization, photo-activation is decoupled from polymerization control, rendering XPI-RAFT an elegant tool for the fabrication of defined and complex macromolecules. The method is oxygen tolerant and robust and was used to perform screenings in a well-plate format, and it was even possible to produce multiblock copolymers in a coffee mug under open-to-air conditions. XPI-RAFT does not rely on highly specialized equipment and qualifies as a universal tool for the straightforward synthesis of complex macromolecules. The method is user-friendly and broadens the scope of what can be achieved with photo-polymerization techniques.

Hybrid fabrication of multimodal intracranial implants for electrophysiology and local drug delivery.

New fabrication approaches for mechanically flexible implants hold the key to advancing the applications of neuroengineering in fundamental neuroscience and clinic. By combining the high precision of thin film microfabrication with the versatility of additive manufacturing, we demonstrate a straight-forward approach for the prototyping of intracranial implants with electrode arrays and microfluidic channels. We show that the implant can modulate neuronal activity in the hippocampus through localized drug delivery, while simultaneously recording brain activity by its electrodes. Moreover, good implant stability and minimal tissue response are seen one-week post-implantation. Our work shows the potential of hybrid fabrication combining different manufacturing techniques in neurotechnology and paves the way for a new approach to the development of multimodal implants.

Conducting Polymer-Ionic Liquid Electrode Arrays for High-Density Surface Electromyography.

Surface electromyography (EMG) is used as a medical diagnostic and to control prosthetic limbs. Electrode arrays that provide large-area, high density recordings have the potential to yield significant improvements in both fronts, but the need remains largely unfulfilled. Here, digital fabrication techniques are used to make scalable electrode arrays that capture EMG signals with mm spatial resolution. Using electrodes made of poly(3,4-ethylenedioxythiophene) polystyrene sulfonate (PEDOT:PSS) composites with the biocompatible ionic liquid (IL) cholinium lactate, the arrays enable high quality spatiotemporal recordings from the forearm of volunteers. These recordings allow to identify the motions of the index, little, and middle fingers, and to directly visualize the propagation of polarization/depolarization waves in the underlying muscles. This work paves the way for scalable fabrication of cutaneous electrophysiology arrays for personalized medicine and highly articulate prostheses.

Microelectrode Arrays for Simultaneous Electrophysiology and Advanced Optical Microscopy.

Advanced optical imaging techniques address important biological questions in neuroscience, where structures such as synapses are below the resolution limit of a conventional microscope. At the same time, microelectrode arrays (MEAs) are indispensable in understanding the language of neurons. Here, the authors show transparent MEAs capable of recording action potentials from neurons and compatible with advanced microscopy. The electrodes are made of the conducting polymer poly(3,4-ethylenedioxythiophene) doped with polystyrene sulfonate (PEDOT:PSS) and are patterned by optical lithography, ensuring scalable fabrication with good control over device parameters. A thickness of 380 nm ensures low enough impedance and >75% transparency throughout the visible part of the spectrum making them suitable for artefact-free recording in the presence of laser illumination. Using primary neuronal cells, the arrays record single units from multiple nearby sources with a signal-to-noise ratio of 7.7 (17.7 dB). Additionally, it is possible to perform calcium (Ca2+) imaging, a measure of neuronal activity, using the novel transparent electrodes. Different biomarkers are imaged through the electrodes using conventional and super-resolution microscopy (SRM), showing no qualitative differences compared to glass substrates. These transparent MEAs pave the way for harnessing the synergy between the superior temporal resolution of electrophysiology and the selectivity and high spatial resolution of optical imaging.

Light-driven molecular trap enables bidirectional manipulation of dynamic covalent systems.

Bond formation between two molecular entities in a closed system strictly obeys the principle of microscopic reversibility and occurs in favour of the thermodynamically more stable product. Here, we demonstrate how light can bypass this fundamental limitation by driving and controlling the reversible bimolecular reaction between an N-nucleophile and a photoswitchable carbonyl electrophile. Light-driven tautomerization cycles reverse the reactivity of the C=O/C=N-electrophiles ('umpolung') to activate substrates and remove products, respectively, solely depending on the illumination wavelength. By applying either red or blue light, selective and nearly quantitative intermolecular bond formation/scission can be achieved, even if the underlying condensation/hydrolysis equilibrium is thermodynamically disfavoured. Exploiting light-driven in situ C=N exchange, our approach can be used to externally regulate a closed dynamic covalent system by actively and reversibly removing specific components, resembling a molecular and bidirectional version of a macroscopic Dean-Stark trap.

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.