Supramolecular assemblies of amphiphilic donor-acceptor Stenhouse adducts as macroscopic soft scaffolds.

In the design of photoharvesting and photoresponsive supramolecular systems in aqueous medium, the fabrication of amphiphilic photoswitches enables a noninvasive functional response through photoirradiation. Although most aqueous supramolecular assemblies are driven by high-energy and biodamaging UV light, we have previously reported a design of amphiphilic donor-acceptor Stenhouse adducts (DASAs) controlled by white light. Herein, we present a series of DASA amphiphiles (DAs) with minor structural modifications on the alkyl linker chain length connecting the DASA motif with the hydrophilic moiety. The excellent photoswitchability in organic medium and the photoresponsiveness in aqueous medium, driven by visible light, were investigated by UV-vis absorption spectroscopy. The assembled supramolecular nanostructures were confirmed by electron microscopy, while the supramolecular packing was revealed by X-ray diffraction analysis. Upon visible-light irradiation, significant transformations of the DA geometry enabled transformations of the supramolecular assemblies on a microscopic scale, subsequently disassembling macroscopic soft scaffolds of DAs. The current work shows promising use for the fabrication of visible-light-controlled macroscopic scaffolds, offering the next generation of biomedical materials with visible-light-controlled microenvironments and future soft-robotic systems.

Aqueous Supramolecular Transformations of Motor Bola-Amphiphiles at Multiple Length-Scale.

Molecular motor amphiphiles have already been widely attempted for dynamic nanosystems across multiple length-scale for developments of small functional materials, including controlling macroscopic foam properties, amplifying motion as artificial molecular muscles, and serving as extracellular matrix mimicking cell scaffolds. However, limiting examples of bola-type molecular motor amphiphiles are considered for constructing macroscopic biomaterials. Herein, this work presents the designed two second generation molecular motor amphiphiles, motor bola-amphiphiles (MBAs). Aside from the photoinduced motor rotation of MBAs achieved in both organic and aqueous media, the rate of recovering thermal helix inversion step can be controlled by the rotor part with different steric hindrances. Dynamic assembled structures of MBAs are observed under (cryo)-transmission electron microscopy (TEM). This dynamicity assists MBAs in further assembling as macroscopic soft scaffolds by applying a shear-flow method. Upon photoirradiation, the phototropic bending function of MBA scaffolds is observed, demonstrating the amplification of molecular motion into macroscopic phototropic bending functions at the macroscopic length-scale. Since MBAs are confirmed with low cytotoxicity, human bone marrow-derived mesenchymal stem cells (hBM-MSCs) can grow on the surface of MBA scaffolds. These results clearly demonstrate the concept of designing MBAs for developing photoresponsive dynamic functional materials to create new-generation soft robotic systems and cell-material interfaces.

Tailoring Multicontrolled Supramolecular Assemblies of Stiff-Stilbene Amphiphiles into Macroscopic Soft Scaffolds as Cell-Material Interfaces.

Biocompatible synthetic supramolecular systems have shed light on biomedical and tissue-regenerative material applications. The intrinsic functional applicability, tunability, and stimuli-responsiveness of synthetic supramolecular systems allow one to develop various multicontrolled supramolecular assemblies in aqueous media. However, it remains highly challenging to use state-of-the-art supramolecular assemblies of photoresponsive amphiphiles controlled by multiple stimulations in fabricating macroscopic materials. Herein, we demonstrate a stiff-stilbene amphiphile (SA) multicontrolled supramolecular assembling system that comprises two different charged end groups. The excellent photoswitchabilities of SA in both organic and aqueous media are demonstrated. Furthermore, multiple stimuli, i.e., light, pH, and counterions, are applied to control the supramolecular assembling behaviors, which are monitored by circular dichroism spectroscopy and electron microscopies. This multicontrolled supramolecular system can be systematically assembled into macroscopic soft functional scaffolds, whose structural parameters are investigated by electron microscopies and X-ray diffraction techniques, suggesting the large aspect ratio of SA nanostructures assembled into macroscopic soft scaffolds. The fabricated soft functional scaffold is highly biocompatible for photocontrolled biotarget encapsulation/release selectively, as well as a cell-material interface for diverse cells' attachment. This new synthetic multicontrolled soft functional material provides a new strategy toward the development of next-generation controllable and biocompatible soft functional materials.

Visible-light controlled supramolecular transformations of donor-acceptor Stenhouse adducts amphiphiles at multiple length-scale.

Designing responsive, adaptive, and dynamic supramolecular systems in water, the incorporation of photoresponsive units in amphiphilic molecular structures enables functional responses in a non-invasive way by using light. However, in aqueous media, vast majority of reported synthetic photoresponsive molecular amphiphiles are commonly driven by high energy and bio-damaging UV-light for supramolecular transformation at multiple length-scale. Herein, we present newly designed visible-light controlled supramolecular assembly of donor-acceptor Stenhouse adducts amphiphiles (DA) with excellent stability and solubility in aqueous media. The excellent photoswitchability in organic media and photoresponsiveness in aqueous media driven by visible-light are found, as confirmed with UV-vis absorption and NMR spectroscopies. Supramolecular assembly at multiple length-scale of DAs is investigated with electron microscopies and X-ray diffraction to show large aspect-ratio of nanostructures assembled into macroscopic soft scaffolds. Upon visible-light irradiation, the large geometrical transformation of DAs enables supramolecular transformations, and subsequently destabilizes the macroscopic soft scaffold to release fluorophores from the scaffolds. These results provide the feasibility in developing the next generation of visible-light controlled macroscopic soft functional scaffold from supramolecular assembly across multiple length-scale without and offer ample opportunity to design future soft robotic materials and functional biomaterials.

2,2-difluorovinyl benzoates for diverse synthesis of gem-difluoroenol ethers by Ni-catalyzed cross-coupling reactions.

gem-Difluoroalkene is a bioisostere of carbonyl group for improving bioavailability of drug candidates. Herein we develop structurally diverse 2,2-difluorovinyl benzoates (BzO-DFs) as versatile building blocks for modular synthesis of gem-difluoroenol ethers (44 examples) and gem-difluoroalkenes (2 examples) by Ni-catalyzed cross coupling reactions. Diverse BzO-DFs derivatives bearing sensitive functional groups (e.g., C = C, TMS, strained carbocycles) are readily prepared from their bromodifluoroacetates and bromodifluoroketones precursors using metallic zinc as reductant. With Ni(COD)2 and dppf [1,1'-bis(diphenylphosphino)ferrocene] as catalyst, reactions of BzO-DFs with arylboronic acids and arylmagnesium/alkylzinc reagents afforded the desired gem-difluoroenol ethers and gem-difluoroalkenes in good yields. The Ni-catalyzed coupling reactions features highly regioselective C(vinyl)-O(benzoate) bond activation of the BzO-DFs. Results from control experiments and DFT calculations are consistent with a mechanism involving initial oxidative addition of the BzO-DFs by the Ni(0) complex. By virtue of diversity of the BzO-DFs and excellent functional group tolerance, this method is amenable to late-stage functionalization of multifunctionalized bioactive molecules.