Dithienothiophenes at Work: Access to Mechanosensitive Fluorescent Probes, Chalcogen-Bonding Catalysis, and Beyond.

In this review, the multifunctionality of dithieno[3,2-b:2',3'-d]thiophenes (DTTs) is covered comprehensively. This is of interest because all involved research is very recent and emphasizes timely topics such as mechanochemistry for bioimaging or chalcogen bonds for catalysis and solar cells and because the newly emerging privileged scaffold is embedded in an inspiring structural space. At the beginning, DTTs are introduced with regard to nomenclature, constitutional isomers, and optoelectronic properties. The structural space around DTTs is mapped out next with regard to heteroatom substitution in the bridge and core, covering much of the periodic table, eccentric heteroatom doping, and bridge expansions. After a brief summary of synthetic approaches to the DTT scaffold, chalcogen bonds are introduced as, together with redox switching and turn-on fluorescence, one of the three conceptual foundations of the most multifunctionality. Realized functions cover anion binding, transport (ion carriers, ion channels), catalysis, and the first fluorescent probes to image physical forces in living cells. The appearance of DTTs in many other photosystems covers push-pull systems for nonlinear optics and dye-sensitized solar cells, DTT polymers in light-emitting diodes, organic field-effect transistors and organic photovoltaics, DTT self-assembly and templated assembly into thin films and fluorescent fibers, also within cells, and the integration of DTTs into photochromes and biaromatics that violate the Hückel rule..

A Chalcogen-Bonding Cascade Switch for Planarizable Push-Pull Probes.

Planarizable push-pull probes have been introduced to demonstrate physical forces in biology. However, the donors and acceptors needed to polarize mechanically planarized probes are incompatible with their twisted resting state. The objective of this study was to overcome this "flipper dilemma" with chalcogen-bonding cascade switches that turn on donors and acceptors only in response to mechanical planarization of the probe. This concept is explored by molecular dynamics simulations as well as chemical double-mutant cycle analysis. Cascade switched flipper probes turn out to excel with chemical stability, red shifts adding up to high significance, and focused mechanosensitivity. Most important, however, is the introduction of a new, general and fundamental concept that operates with non-trivial supramolecular chemistry, solves an important practical problem and opens a wide chemical space.

White-Fluorescent Dual-Emission Mechanosensitive Membrane Probes that Function by Bending Rather than Twisting.

Bent N,N'-diphenyl-dihydrodibenzo[a,c]phenazine amphiphiles are introduced as mechanosensitive membrane probes that operate by an unprecedented mechanism, namely, unbending in the excited state as opposed to the previously reported untwisting in the ground and twisting in the excited state. Their dual emission from bent or "closed" and planarized or "open" excited states is shown to discriminate between micelles in water and monomers in solid-ordered (So ), liquid-disordered (Ld ) and bulk membranes. The dual-emission spectra cover enough of the visible range to produce vesicles that emit white light with ratiometrically encoded information. Strategies to improve the bent mechanophores with expanded π systems and auxochromes are reported, and compatibility with imaging of membrane domains in giant unilamellar vesicles by two-photon excitation fluorescence (TPEF) microscopy is demonstrated.

Artificial cells with viscoadaptive behavior based on hydrogel-loaded giant unilamellar vesicles.

Viscoadaptation is an essential process in natural cells, where supramolecular interactions between cytosolic components drive adaptation of the cellular mechanical features to regulate metabolic function. This important relationship between mechanical properties and function has until now been underexplored in artificial cell research. Here, we have created an artificial cell platform that exploits internal supramolecular interactions to display viscoadaptive behavior. As supramolecular material to mimic the cytosolic component of these artificial cells, we employed a pH-switchable hydrogelator based on poly(ethylene glycol) coupled to ureido-pyrimidinone units. The hydrogelator was membranized in its sol state in giant unilamellar lipid vesicles to include a cell-membrane mimetic component. The resulting hydrogelator-loaded giant unilamellar vesicles (designated as HL-GUVs) displayed reversible pH-switchable sol-gel behavior through multiple cycles. Furthermore, incorporation of the regulatory enzyme urease enabled us to increase the cytosolic pH upon conversion of its substrate urea. The system was able to switch between a high viscosity (at neutral pH) and a low viscosity (at basic pH) state upon addition of substrate. Finally, viscoadaptation was achieved via the incorporation of a second enzyme of which the activity was governed by the viscosity of the artificial cell. This work represents a new approach to install functional self-regulation in artificial cells, and opens new possibilities for the creation of complex artificial cells that mimic the structural and functional interplay found in biological systems.

Pnictogen-Bonding Catalysis and Transport Combined: Polyether Transporters Made In Situ.

The combination of catalysis and transport across lipid bilayer membranes promises directional access to a solvent-free and structured nanospace that could accelerate, modulate, and, at best, enable new chemical reactions. To elaborate on these expectations, anion transport and catalysis with pnictogen and tetrel bonds are combined with polyether cascade cyclizations into bioinspired cation transporters. Characterized separately, synergistic anion and cation transporters of very high activity are identified. Combined for catalysis in membranes, cascade cyclizations are found to occur with a formal rate enhancement beyond one million compared to bulk solution and product formation is detected in situ as an increase in transport activity. With this operational system in place, intriguing perspectives open up to exploit all aspects of this unique nanospace for important chemical transformations.