3-(2-Carboxyethyl)indole-2-carboxylic Acid Derivatives: Structural Requirements and Properties of Potent Agonists of the Orphan G Protein-Coupled Receptor GPR17.

The orphan receptor GPR17 may be a novel drug target for inflammatory diseases. 3-(2-Carboxyethyl)-4,6-dichloro-1 H-indole-2-carboxylic acid (MDL29,951, 1) was previously identified as a moderately potent GPR17 agonist. In the present study, we investigated the structure-activity relationships (SARs) of 1. Substitution of the indole 1-, 5-, or 7-position was detrimental. Only small substituents were tolerated in the 4-position while the 6-position accommodated large lipophilic residues. Among the most potent compounds were 3-(2-carboxyethyl)-1 H-indole-2-carboxylic acid derivatives containing the following substituents: 6-phenoxy (26, PSB-1737, EC50 270 nM), 4-fluoro-6-bromo (33, PSB-18422, EC50 27.9 nM), 4-fluoro-6-iodo (35, PSB-18484, EC50 32.1 nM), and 4-chloro-6-hexyloxy (43, PSB-1767, EC50 67.0 nM). (3-(2-Carboxyethyl)-6-hexyloxy-1 H-indole-2-carboxylic acid (39, PSB-17183, EC50 115 nM) behaved as a partial agonist. Selected potent compounds tested at human P2Y receptor subtypes showed high selectivity for GPR17. Docking into a homology model of the human GPR17 and molecular dynamic simulation studies rationalized the observed SARs.

A Conjugated Microporous Polymer for Palladium-Free, Visible Light-Promoted Photocatalytic Stille-Type Coupling Reactions.

The Stille coupling reaction is a versatile method to mainly form aromatic C-C bonds. However, up to now, the use of palladium catalysts is necessary. Here, a palladium-free and photocatalytic Stille-type coupling reaction of aryl iodides and aryl stannanes catalyzing a conjugated microporous polymer-based phototcatalyst under visible light irradiation at room temperature is reported. The novel coupling reaction mechanism occurs between the photogenerated aryl radical under oxidative destannylation of the aryl stannane, and the electron-activated aryl iodide, resulting into the aromatic C-C bond formation reaction. The visible light-promoted Stille-type coupling reaction using the polymer-based pure organic photocatalyst offers a simple, sustainable, and more economic synthetic pathway toward palladium-free aromatic C-C bond formation.

Molecular Engineering of Conjugated Polybenzothiadiazoles for Enhanced Hydrogen Production by Photosynthesis.

The search for metal-free organic photocatalysts for H2 production from water using visible light remains a key challenge. Reported herein is a molecular structural design of pure organic photocatalysts, derived from conjugated polybenzothiadiazoles, for photocatalytic H2 evolution using visible light. By alternating the substitution position of the electron-withdrawing benzothiadizole unit on the phenyl unit as a comonomer, various polymers with either one- or three-dimensional structures were synthesized and the effect of the molecular structure on their catalytic activity was investigated. Photocatalytic H2 evolution efficiencies up to 116 µmol h(-1) were observed by employing the linear polymer based on a phenyl-benzothiadiazole alternating main chain, with an apparent quantum yield (AQY) of 4.01 % at 420 nm using triethanolamine as the sacrificial agent.

Enhanced visible light promoted antibacterial efficiency of conjugated microporous polymer nanoparticles via molecular doping.

The increase in the resistance of bacteria to antibiotics is one of the main concerns of public health and holds a great demand in the development of new disinfection methods. Photodynamic therapy (PDT) has been considered as a promising alternative approach towards the eradication of bacteria and great attention has been dedicated to the use of non-toxic and pure organic PDT agents. Herein we report the structural design method of a series of conjugated microporous polymer nanoparticles (CMP NPs) as a new class of highly effective photoactive materials for the inactivation of bacteria in water upon visible light exposure. Through molecular doping of electron-withdrawing moieties into electron-donating polymer backbones, enhanced antibacterial properties are demonstrated upon the inactivation of Escherichia coli K-12 and Bacillus subtilis mainly by means of photogeneration of singlet oxygen as the main photogenerated active species. Additionally, the high stability, reusability and disinfection mechanism of the CMP NPs are also described.

Heterophase Photocatalysts from Water-Soluble Conjugated Polyelectrolytes: An Example of Self-Initiation under Visible Light.

We herein report a new design route to stable, heterophase photocatalysts, which function as highly dispersible conjugated polymer nanoparticles and porous monoliths under visible light in aqueous medium. They were constructed by attachment of the ionic-liquid species 1-alkyl-3-vinylimidazolium bromide onto the side chains of a photoactive polymer. The structure configuration allows not only photocatalysis in aqueous environment but also a unique self-initiation radical cross-linking process to transform the water-soluble photoactive polymer into a heterophase system, either as nanoparticles or a porous monolith. High photocatalytic activity and reusability of the heterophase system were demonstrated in the degradation of organic dyes and reduction of Cr(VI) into Cr(III) in water under visible-light irradiation.

Conjugated Microporous Poly(Benzochalcogenadiazole)s for Photocatalytic Oxidative Coupling of Amines under Visible Light.

Metal-free visible-light photocatalysts offer a clean, sustainable solution to many pressing environmental issues. Herein, we present a molecular design strategy to fine-tune the valence and conduction band levels of a series of conjugated microporous polymer networks based on poly(benzochalcogenadiazole) for heterogeneous photocatalysis. Enhanced photocatalytic efficiency was observed by altering the chalcogene moieties in the electron-accepting benzochalcogenadiazole unit of the polymer backbone structure. Photooxidative coupling of benzylamines was chosen as a model reaction. This design strategy leading to enhanced efficiency could potentially improve a wide range of photoredox reactions.

Molecular Structural Design of Conjugated Microporous Poly(Benzooxadiazole) Networks for Enhanced Photocatalytic Activity with Visible Light.

A simple structural design principle and band position alignment of conjugated microporous polymers for enhanced photocatalytic efficiency is presented. The valence and conduction band positions of the polymer networks can be fine-tuned by altering the substitution positions on the centered phenyl unit to match the required redox potential of the catalytic reactions under visible light.

Polyfluorene polyelectrolyte nanoparticles: synthesis of innovative stabilizers for heterophase polymerization.

Polyfluorene-bearing bromohexyl side chains are quaternized by 1-vinylimidazole in order to attach dialkylimidazolium bromide ionic liquid (IL) species along the conjugated backbone. Subsequently, polyfluorene polyelectrolyte nanoparticles (NPs) of 40 nm in average size are created via radical cross-linking of the pendant vinylimidazolium groups. Anion exchange from Br(-) to BF(4)(-), PF(6)(-), and bis(trifluoromethylsulfonyl)imide anion (TFSI(-) renders NPs adjustable dispersability in various organic solvents. The hydrophobic-conjugated backbone and the hydrophilic dialkylimidazolium bromide IL moieties depict an amphiphilic profile, which allows the NPs to be deployed as conductive stabilizer in the emulsion polymerization of styrene. The resultant latexes are fluorescent, tunable in size and can be transferred to organic solvents without forfeiting their colloidal stability.

Highly porous conjugated polymers for selective oxidation of organic sulfides under visible light.

High surface area porous conjugated polymers were synthesized via the high internal phase emulsion polymerization technique and micropore engineering as efficient heterogeneous photocatalysts for highly selective oxidation of organic sulfides to sulfoxides under visible light.