Non-emissive RuII Polypyridyl Complexes as Efficient and Selective Photosensitizers for the Photooxidation of Benzylamines

RTI2018-100709-B-C21 CTQ (QMC)-RED2018-102471-T) Junta de Castilla y Leon (BU087G19 FEDER (BU042U16-BU305P18).Five new RuII polypyridyl complexes bearing N-(arylsulfonyl)-8-amidoquinolate ligands and three of their biscyclometalated IrIII congeners have been prepared and employed as photocatalysts (PCs) in the photooxidation of benzylamines with O2. In particular, the new RuII complexes do not exhibit photoluminescence, rather they harvest visible light efficiently and are very stable in solution under irradiation with blue light. Their non-emissive behavior has been related to the low electrochemical energy gaps and rationalized on the basis of theoretical calculations (DFT analysis) that predict low S0←T1 energy values. Moreover, the RuII complexes, despite being non-emissive, display excellent activities in the selective photocatalytic transformation of benzylamines into the corresponding imines. The presence of an electron-withdrawing group (-CF3) on the arene ring of the N-(arylsulfonyl)-8-amidoquinolate ligand improves the photocatalytic activity of the corresponding photocatalyst. Furthermore, all the experimental evidence, including transient absorption spectroscopy measurements suggest that singlet oxygen is the actual oxidant. The IrIII analogues are considerably more photosensitive and consequently less efficient photosensitizers (PSs).authorsversionpublishe

Biological activity and photocatalytic properties of a naphthyl-imidazo phenanthroline (HNAIP) ligand and its [Ir(ppy)2(HNAIP)]Cl and [Rh(ppy)2(HNAIP)]Cl complexes

The synthesized 2-(hydroxy-1-naphtyl)imidazo-[4,5-f][1,10]phenanthroline (HNAIP) ligand and its new iridium ([Ir(ppy)2(HNAIP)]Cl) and rhodium ([Rh(ppy)2(HNAIP)]Cl) complexes, being ppy = 2-phenylpiridinate, show cytotoxic effects in SW480 (colon adenocarcinoma) and A549 (epithelial lung adenocarcinoma) cells. They all are cytotoxic in the tested cell lines. HNAIP and [Rh(ppy)2(HNAIP)]+ are the most cytotoxic, whereas [Ir(ppy)2(HNAIP)]+ displays negligible cytotoxicity towards A549 cells and moderate activity towards SW480. The interaction of all three compounds with Bovine Serum Albumin (BSA), l-glutathione reduced (GSH), nicotinamide adenine dinucleotide (NADH) and DNA was studied to explain the differences found in terms of cytotoxicity. None of them are able to interact with BSA, thus excluding bioavailability due to plasma protein interaction as the possible differentiating factor in their biological activity. By contrast, small differences have been observed regarding DNA interaction. In addition, taking advantage of the emission properties of these molecules, they have been visualized in the cytoplasmic region of A549 cells. Inductively coupled plasma mass spectrometry (ICP-MS) experiments show, in turn, that the internalization ability follow the sequence [Rh(ppy)2(HNAIP)]+ > [Ir(ppy)2(HNAIP)]+ > cisplatin. Therefore, it seems clear that the cellular uptake by tumour cells is the key factor affecting the different cytotoxicity of the metal complexes and that this cellular uptake is influenced by the hydrophobicity of the studied complexes. On the other hand, preliminary catalytic experiments performed on the photo-oxidation of GSH and some amino acids such as l-methionine (Met), l-cysteine (Cys) and l-tryptophan (Trp) provide evidence for the photocatalytic activity of the Ir(III) complex in this type of reactions.“la Caixa” Banking Foundation (LCF/PR/PR12/11070003), Ministerio de Ciencia, Innovación y Universidades (RTI2018-102040-B-100 and RTI2018-100709-B-C21), Junta de Castilla y León (BU305P18, FEDER Funds

Síntesis y caracterización de complejos metálicos de Ir(III), Rh(III) y Ru(II). Estudio de su actividad citotóxica en células cancerígenas y de su uso en reacciones de (des)hidrogenación catalítica por transferencia

En esta tesis se aborda la síntesis, caracterización y el estudio químico, químico–físico y biológico de distintos complejos metálicos de rutenio(II), iridio(III) y rodio(III) para investigar su potencial uso en dos aplicaciones con una gran relevancia en nuestra sociedad actual: el tratamiento quimioterapéutico contra el cáncer y la catálisis en reacciones de hidrogenación/deshidrogenación. Parte 1. Complejos metálicos de Ru(II), Ir(III) y Rh(III) con actividad antiproliferativa en células cancerígenas y en bacterias. En los primeros capítulos de la tesis se detalla la síntesis, caracterización y estudio de las propiedades físico – químicas de los complejos metálicos sintetizados (mononucleares y dinucleares). Todos los complejos cuentan con un ligando de tipo aril-imidazo-fenantrolina También se ha evaluado su citotoxicidad en células de adenocarcinoma de colón (SW480) y adenocarcinoma epitelial de pulmón (A549), y su actividad antimicrobiana frente patógenos ESKAPE (principal causa de infecciones nosocomiales). Finalmente, se exploran los mecanismos a través de los cuales ejercen su actividad biológica, la cual puede ser de diversa naturaleza. Estos estudios tienen como objetivo principal entender los factores que son determinantes en la actividad biológica de los compuestos, permitiendo avanzar en el diseño racional de nuevos fármacos capaces de mejorar la eficacia de los tratamientos existentes. Parte 2. Complejos organometálicos de Ru(II), Ir(III) y Rh(III) en reacciones de (des)hidrogenación catalítica. Por otro lado, se ha sintetizado una familia de complejos organometálicos de tipo half-sandwich con ligandos quelantes de tipo κ2 -N,N’ con el objetivo de estudiar su actividad catalítica en reacciones de transferencia de hidrógeno. Algunos de los complejos han resultado ser activos en tres procesos que implican la transferencia concertada de hidruros y protones: la hidrogenación de CO2, la deshidrogenación de ácido fórmico y la hidrogenación de 2-metilquinolinas. En todos estos procesos, la presencia de un grupo -NH2 coordinado al centro metálico resultó jugar un papel clave

Cytotoxic activity and G-quadruplex stabilization of Ir(III) complexes with phenanthroimidazole derivative ligands

Resumen del póster presentado a la 24th Virtual Conference on Organometallic Chemistry (EuCOMC XXIV Virtual Conference), celebrada del 1 al 3 de septiembre de 2021.Metal complexes are playing an important role over the last few years in the design of new fluorophores with potential application in cell imaging and cancer therapy. Focusing on DNA as the cellular target, G-quadruplex DNA-forming sequences have attracted great attention because they are involved in several biological processes, from chromosome protection to senescence process. In fact, the higher prevalence of these structures in cancer cells than in normal cells, link G4 structures with cancer. So a growing interest is devoted to drugs with a good affinity for G4-DNA and selectivity towards G-quadruplex over duplex DNA to enhance and/or promote quadruplex-related biological effects.Bearing in mind the above-mentioned, we have synthesized a couple of Ir(III) biscyclometallated phosphorescent complexes, [Ir1]Cl and [Ir2]Cl, which incorporate two different imidazolephenanthroline ligands, L1 and L2, where L1 holds an acidic N-H group, while L2 is decorated with a N-Ph group. As shown in this work, such a trivial functional change influences the acidbase and redox chemistry of [Ir1]Cl and [Ir2]Cl, and what is more interesting, it also affects the subcellular localization of these derivatives, their cytotoxic behaviour and their mechanism of action. Finally, both complexes are able to stabilize a battery of G4 structures with preference for antiparallel two-tetrads G4 (Bom17 and TBA). In addition, [Ir1]Cl exhibits selectivity for G-quadruplex even in the presence of a DNA double helix as competitor revealing the potential of this complex for specifically target G4 structures.The authors thank “La Caixa” Foundation (LCF/PR/PR12/11070003), Junta de Castilla y León (BU305P18, FEDER Funds and ORDEN EDU/574/2018) and ministerio de Ciencia, Innovación y Universidades (RTI2018- 100709-B-C21 , RTI2018-102040-B-100 and RED2018-102471-T). Networking support by COST Action CA18202 (NECTAR) is also acknowledged.Peer reviewe