Red Absorbing Cyclometalated Ir(III) Diimine Photosensitizers Competent for Hydrogen Photocatalysis.

Two new cyclometalated Ir(III) diimine complexes were used as photosensitizers for homogeneous hydrogen evolution reaction (HER). These complexes were characterized by electrochemistry, ultraviolet-visible absorption, time-resolved and steady-state photoluminescence spectroscopy as well as by theoretical methods. The metal-ligand-to-ligand charge transfer character of their lowest excited state was shown to be competent for efficient H2 photoproduction in the presence of [Co(dmgH)2(py)Cl] as the hydrogen evolution catalyst, triethanolamine as the sacrificial electron donor, and HBF4 as the proton source. Under optimized experimental conditions, both complexes displayed HER over a period of more than 90 h, with turnover numbers reaching up to 11,650, 10,600, and 174 molH2 molPS-1 under blue-, green-, and red-light irradiation, respectively. Both complexes showed higher stability and efficiency vs HER than most of the previously described systems of the same kind.

A Smorgasbord of 17 Cobalt Complexes Active for Photocatalytic Hydrogen Evolution.

Seventeen cobalt complexes-eleven dinuclear cobalt(II) complexes and three tetranuclear cobalt complexes (two mixed valent) of ditopic ligands, with varying N-donor aromatic bridging moieties and pendant pyridine side arms, as well as three mononuclear cobalt(II) complexes of Schiff base macrocyclic ligands-have been screened for photocatalytic hydrogen evolution reaction (HER) activity. All 17 complexes are active catalysts for the HER, in both DMF and aqueous solution, in tandem with the [Ru(bpy)3 ]2+ (bpy=2,2'-bipyridine) photosensitiser. All are benchmarked to the literature standard [CoIII (dmgH)2 (py)Cl] (dmg=dimethylglyoxime, py=pyridine) under identical conditions. Two families of dinuclear cobalt(II) complexes of bis-tetradentate ligands that provide a triazole bridging moiety and mononuclear cobalt(II) complexes of tetradentate Schiff base macrocycles were found to be the most active catalysts, outperforming [CoIII (dmgH)2 (py)Cl] by two- to three-fold. Within these two families, the use of shorter alkyl linkers between the N donors, and hence, smaller chelate ring sizes, was found to significantly enhance catalytic performance, whereas the variation of peripheral functional groups was found to have little effect. This last point will be convenient for subsequent surface immobilisation studies.

Photocatalytic Hydrogen Production Using a Red-Absorbing Ir(III)-Co(III) Dyad.

The synthesis of a Ir(III)-Co(III) dyad with vectorial electron transfer afforded a novel supramolecular system that photocatalytically produces hydrogen in a range extending from the blue region of the spectrum to the red region with higher turnover number and frequency compared to other bimetallic dyads.

Pt(II)-bis(quinolinyl) complexes for photocatalytic hydrogen production.

Three Pt(II)-bis(quinolinyl) complexes with varying electron densities were synthesized, structurally characterized and used for photocatalytic hydrogen production under different conditions. All the complexes were found to be active for hydrogen production giving a maximum turnover number (TON) of 1230 surpassing the conventionally used Pt-terpyridyl complexes.

Discovery of a novel series of potent S1P1 agonists.

The discovery of a novel series of S1P1 agonists is described. Starting from a micromolar HTS positive, iterative optimization gave rise to several single-digit nanomolar S1P1 agonists. The compounds were able to induce internalization of the S1P1 receptor, and a selected compound was shown to be able to induce lymphopenia in mice after oral dosing.

Mimicking 2,2':6',2'':6'',2'''-quaterpyridine complexes for the light-driven hydrogen evolution reaction: synthesis, structural, thermal and physicochemical characterizations.

The synthetic difficulties associated with quaterpyridine (qtpy) complexes have limited their use in the formation of various metallosupramolecular architectures in spite of their diverse structural and physicochemical properties. Providing a new facile synthetic route to the synthesis of functionalised qtpy mimics, we herein report the synthesis of three novel -NH2 functionalized qtpy-like complexes 12-14 with the general formula M(C16H14N12)(NO3)2 (M = Co(ii), Ni(ii) and Cu(ii)) in high yield and purity. Characterization of these complexes has been done by single crystal X-ray diffraction (SCXRD), thermogravimetric analysis, UV-Vis, infrared, mass spectrometry and cyclic voltammetry. As indicated by SCXRD, in all the synthesized complexes, the metal ions show a strongly distorted octahedral coordination geometry and typical hydrogen bonding networks involving DAT groups. In addition, complexes 12-14 have been analyzed as potential photocatalysts for hydrogen evolution reaction (HER) displaying good turnover numbers (TONs). Hydrogen produced from these photocatalysts can serve as the possible alternative for fossil fuels. To the best of our knowledge, this is the only study showcasing -NH2 functionalized qtpy-like complexes of Co(ii), Ni(ii) and Cu(ii) and employing them as photocatalysts for HER. Thus, a single proposed strategy solves two purposes-one related to synthesis while second is related to our environment.

Design and photophysical studies of iridium(iii)-cobalt(iii) dyads and their application for dihydrogen photo-evolution.

We report several new dyads constituted of cationic iridium(iii) photosensitizers and cobalt(iii) catalyst connected via free pendant pyridine on the photosensitizers. These dyads were studied by X-ray crystallography, electrochemistry, absorption and emission spectroscopy as well as theoretical calculations and were shown to efficiently produce H2 under visible light irradiation. In every case, the dyad outperformed the equivalent system without a pendant pyridine. The dependence between irradiation wavelength and photocatalytic performances was also studied, with H2 being evolved with turn-over numbers up to 295, 251, 188 and 78 molH2 molPS-1 under blue, green, yellow and red light, respectively.

A Bisamide Ruthenium Polypyridyl Complex as a Robust and Efficient Photosensitizer for Hydrogen Production.

A photosensitizer based on a ruthenium complex of a bisamide-polypyridyl ligand gives rise to a large improvement in photocatalytic stability, rate of activity, and efficiency in photocatalytic H2 production compared to [Ru(bpy)3 ]2+ (bpy=2,2'-bpyridine). The bisamide ruthenium polypyridyl complex combined with a cobaltoxime-based photocatalyst was found to be highly efficient under blue-light (turnover number (TON)=7800) and green-light irradiation (TON=7200) whereas [Ru(bpy)3 ]2+ was significantly less effective with a TON of 2600 and 1100, respectively. The greatest improvement was under red-light-emitting diodes, with bisamide ruthenium polypyridyl complex and cobaltoxime exhibiting a TON of 4200 compared to [Ru(bpy)3 ]2+ and cobaltoxime at a TON of only 71.

Discovery of a Novel Series of CRTH2 (DP2) Receptor Antagonists Devoid of Carboxylic Acids.

Antagonism of the CRTH2 receptor represents a very attractive target for a variety of allergic diseases. Most CRTH2 antagonists known to date possess a carboxylic acid moiety, which is essential for binding. However, potential acid metabolites O-acyl glucuronides might be linked to idiosynchratic toxicity in humans. In this communication, we describe a new series of compounds that lack the carboxylic acid moiety. Compounds with high affinity (K i < 10 nM) for the receptor have been identified. Subsequent optimization succeeded in reducing the high metabolic clearance of the first compounds in human and rat liver microsomes. At the same time, inhibition of the CYP isoforms was optimized, giving rise to stable compounds with an acceptable CYP inhibition profile (IC50 CYP2C9 and 2C19 > 1 µM). Taken together, these data show that compounds devoid of carboxylic acid groups could represent an interesting alternative to current CRTH2 antagonists in development.

Discovery of potent, selective, and orally bioavailable alkynylphenoxyacetic acid CRTH2 (DP2) receptor antagonists for the treatment of allergic inflammatory diseases.

New phenoxyacetic acid antagonists of CRTH2 are described. Following the discovery of a hit compound by a focused screening, high protein binding was identified as its main weakness. Optimization aimed at reducing serum protein binding led to the identification of several compounds that showed not only excellent affinities for the receptor (41 compounds with K(i) < 10 nM) but also excellent potencies in a human whole blood assay (IC(50) < 100 nM; PGD2-induced eosinophil shape change). Additional optimization of the PK characteristics led to the identification of several compounds suitable for in vivo testing. Of these, 19k and 19s were tested in two different pharmacological models (acute FITC-mediated contact hypersensitivity and ovalbumin-induced eosinophilia models) and found to be active after oral dosing (10 and 30 mg/kg).