Ruthenium-based PACT agents based on bisquinoline chelates: synthesis, photochemistry, and cytotoxicity

The known ruthenium complex [Ru(tpy)(bpy)(Hmte)](PF6)(2) ([1](PF6)(2), where tpy = 2,2':6',2 ''-terpyridine, bpy = 2,2'-bipyridine, Hmte = 2-(methylthio)ethanol) is photosubstitutionally active but non-toxic to cancer cells even upon light irradiation. In this work, the two analogs complexes [Ru(tpy)(NN)(Hmte)](PF6)(2), where NN = 3,3'-biisoquinoline (i-biq, [2](PF6)(2)) and di(isoquinolin-3-yl)amine (i-Hdiqa, [3](PF6)(2)), were synthesized and their photochemistry and phototoxicity evaluated to assess their suitability as photoactivated chemotherapy (PACT) agents. The increase of the aromatic surface of [2](PF6)(2) and [3](PF6)(2), compared to [1](PF6)(2), leads to higher lipophilicity and higher cellular uptake for the former complexes. Such improved uptake is directly correlated to the cytotoxicity of these compounds in the dark: while [2](PF6)(2) and [3](PF6)(2) showed low EC50 values in human cancer cells, [1](PF6)(2) is not cytotoxic due to poor cellular uptake. While stable in the dark, all complexes substituted the protecting thioether ligand upon light irradiation (520 nm), with the highest photosubstitution quantum yield found for [3](PF6)(2) (phi([3]) = 0.070). Compounds [2](PF6)(2) and [3](PF6)(2) were found both more cytotoxic after light activation than in the dark, with a photo index of 4. Considering the very low singlet oxygen quantum yields of these compounds, and the lack of cytotoxicity of the photoreleased Hmte thioether ligand, it can be concluded that the toxicity observed after light activation is due to the photoreleased aqua complexes [Ru(tpy)(NN)(OH2)](2+), and thus that [2](PF6)(2) and [3](PF6)(2) are promising PACT candidates.[GRAPHICS].Metals in Catalysis, Biomimetics & Inorganic Material

Co-operative and frustration effects in novel perovskite-related phases

We report on magnetic and electronic properties of various perovskite-type oxides containing 4d- and 5d-transition metals. The compounds under investigation crystallize in (distorted) cubic, layered, and hexagonal perovskite-related structures. These changes in structural dimensionality are reflected by different ordering phenomena. (Pseudo-) cubic perovskites AC