Amphiphilic Metallodrug Assemblies with Red-Light-Enhanced Cellular Internalization and Tumor Penetration for Anticancer Phototherapy.

Metallodrugs are widely used in cancer treatment. The modification of metallodrugs with polyethylene glycol (PEGylation) prolongs blood circulation and improves drug accumulation in tumors; it represents a general strategy for drug delivery. However, PEGylation hinders cellular internalization and tumor penetration, which reduce therapeutic efficacy. Herein, the red-light-enhanced cellular internalization and tumor penetration of a PEGylated anticancer agent, PEGylated Ru complex (Ru-PEG), are reported upon. Ru-PEG contains a red-light-cleavable PEG ligand, anticancer Ru complex moiety, and fluorescent pyrene group for imaging and self-assembly. Ru-PEG self-assembles into vesicles that circulate in the bloodstream and accumulate in the tumors. Red-light irradiation induces dePEGylation and changes the Ru-PEG vesicles to large compound micelles with smaller diameters and higher zeta potentials, which enhance tumor penetration and cellular internalization. Red-light irradiation also generates intracellular 1 O2 , which induces the death of cancer cells. This work presents a new strategy to enhance the cellular internalization and tumor penetration of anticancer agents for efficient phototherapy.

Ru-Se Coordination: A New Dynamic Bond for Visible-Light-Responsive Materials.

Photodynamic bonds are stable in the dark and can reversibly dissociate/form under light irradiation. Photodynamic bonds are promising building blocks for responsive or healable materials, photoactivated drugs, nanocarriers, extracellular matrices, etc. However, reactive intermediates from photodynamic bonds usually lead to side reactions, which limit the use of photodynamic bonds. Here, we report that the Ru-Se coordination bond is a new photodynamic bond that reversibly dissociates under mild visible-light-irradiation conditions. We observed that Ru-Se bonds form via the coordination of a selenoether ligand with [Ru(tpy)(biq)(H2O)]Cl2 (tpy = 2,2':6',2″-terpyridine, biq = 2,2'-biquinoline) in the dark, while the Ru-Se bond reversibly dissociates under visible-light irradiation. No side reaction is detected in the formation and dissociation of Ru-Se bonds. To demonstrate that the Ru-Se bond is applicable to different operating environments, we prepared photoresponsive amphiphiles, surfaces, and polymer gels using Ru-Se bonds. The amphiphiles with Ru-Se bonds showed reversible morphological transitions between spherical micelles and bowl-shaped assemblies for dark/light irradiation cycles. The surfaces modified with Ru-Se-bond-containing compounds showed photoswitchable wettability. Polymer gels with Ru-Se cross-links underwent photoinduced reversible sol-gel transitions, which can be used for reshaping and healing. Our work demonstrates that the Ru-Se bond is a new type of dynamic bond, which can be used for constructing responsive, reprocessable, switchable, and healable materials that work in a variety of environments.

Radical Borylation/Cyclization Cascade of 1,6-Enynes for the Synthesis of Boron-Handled Hetero- and Carbocycles.

A synthetic method to construct boron-handled cyclic molecules was developed based on a radical borylation/cyclization cascade of 1,6-enynes. The process was initiated by the chemo- and regio-controlled addition of an N-heterocyclic carbene-boryl radical to an alkene or alkyne, followed by ring closure to afford boron-substituted cyclic skeletons. Further molecular transformations of the cyclic products to synthetically useful building blocks were also demonstrated.

Reconfiguring hydrogel assemblies using a photocontrolled metallopolymer adhesive for multiple customized functions.

Stimuli-responsive hydrogels with programmable shape changes are promising materials for soft robots, four-dimensional printing, biomedical devices and artificial intelligence systems. However, these applications require the fabrication of hydrogels with complex, heterogeneous and reconfigurable structures and customizable functions. Here we report the fabrication of hydrogel assemblies with these features by reversibly gluing hydrogel units using a photocontrolled metallopolymer adhesive. The metallopolymer adhesive firmly attached individual hydrogel units via metal-ligand coordination and polymer chain entanglement. Hydrogel assemblies containing temperature- and pH-responsive hydrogel units showed controllable shape changes and motions in response to these external stimuli. To reconfigure their structures, the hydrogel assemblies were disassembled by irradiating the metallopolymer adhesive with light; the disassembled hydrogel units were then reassembled using the metallopolymer adhesive with heating. The shape change and structure reconfiguration abilities allow us to reprogramme the functions of hydrogel assemblies. The development of reconfigurable hydrogel assemblies using reversible adhesives provides a strategy for designing intelligent materials and soft robots with user-defined functions.

Reversible Crosslinking of Commodity Polymers via Photocontrolled Metal-Ligand Coordination for High-Performance and Recyclable Thermoset Plastics.

Thermoset plastics, highly desired for their stability, durability, and chemical resistance, are currently consumed in over 60 million tons annually across the globe, but they are difficult to recycle due to their crosslinked structures. The development of recyclable thermoset plastics is an important but challenging task. In this work, recyclable thermoset plastics are prepared by crosslinking a commodity polymer, polyacrylonitrile (PAN), with a small percentage of a Ru complex via nitrile-Ru coordination. PAN is obtained from industry and the Ru complex is synthesized in one step, which enables the production of recyclable thermoset plastics in an efficient way. In addition, the thermoset plastics exhibit impressive mechanical performance, boasting a Young's modulus of 6.3 GPa and a tensile strength of 109.8 MPa. Moreover, they can be de-crosslinked when exposed to both light and a solvent and can then be re-crosslinked upon heating. This reversible crosslinking mechanism enables the recycling of thermosets from a mixture of plastic waste. The preparation of recyclable thermosets from other commodity polymers such as poly(styrene-coacrylonitrile) (SAN) resins and polymer composites through reversible crosslinking is also demonstrated. This study shows that reversible crosslinking via metal-ligand coordination is a new strategy for designing recyclable thermosets using commodity polymers.

Regioselective radical hydroboration of electron-deficient alkenes: synthesis of α-boryl functionalized molecules.

A regioselective radical hydroboration of various electron-deficient alkenes is achieved by the employment of an NHC-boryl radical. A range of α-borylated nitriles, trifluoromethyl molecules, phosphonates, sulfones, and gem-diboron compounds have been prepared from readily available starting materials. Further synthetic applications of these products are also demonstrated.

Radical Borylative Cyclization of 1,6-Dienes: Synthesis of Boron-Substituted Six-Membered Heterocycles and Carbocycles.

A radical borylative cyclization reaction of 1,6-dienes was developed to assemble boron-handled six-membered heterocycles and carbocycles. This reaction was initiated by the chemo- and regio-controlled addition of an N-heterocyclic carbene-boryl radical to one of the alkene tethers, followed by an intramolecular 6- exo cyclization to afford a six-membered ring framework. The utility of this method was demonstrated in the synthesis of diverse paroxetine analogues through late-stage derivatization of the boryl functional unit.