Synthesis and Photophysical Properties of Cycloplatinated(II) Complexes Bearing Isocyanide and Alkynyl Ligands

Cyclometalated platinum(II) complexes havegained increasing interest during the last yearsdue to their rich chemistry and uniqueluminescent properties, making them suitablefor light emitting diodes (OLEDs),photocatalysis, bioimaging or chemicalsensors. However, there are very scarceantecedents of heteroleptic cycloplatinated(II)compounds with isocyanide and alkynylligands.1To expand this research, we aimed to prepare anew family of luminescent cycloplatinatedcomplexes with 2-(2,4-difluorophenyl)pyridine(dfppy, a) and 4-(2-pyridyl)benzaldehyde(ppy-CHO, b) as cyclometalating ligands. Thealkynyl/tert-butyl isocyanide complexes[Pt(C^N)(CCR)(CNtBu)], bearing 4-ethynylanisole (2) and 2-ethynylthiophene (3)have obtained from the chloride derivatives[Pt(C^N)Cl(CNtBu)] (C^N = dfppy 1a, ppy-CHO 1b) using the Sonogashira protocol.These systems have been designed by takinginto account features that could make thesecomplexes interesting in biological studies.The complexes have been fully characterizedusing NMR spectroscopy together with X-raydiffraction. Their optical properties have beenstudied in detail and interpreted with the helpof TD-DFT calculations. The dfppy derivativesexhibit a mechanochromic behaviour, relatedto their strong tendency to form stackingstructures or aggregates by Pt···Pt and/or ···interactions

Structural and Chromic Behaviour of Cycloplatinated(II) Complexes Bearing Isocyanide Ligands

Cyclometalated platinum(II) complexes have received extensive attention due to theirproperties, such as long emissive lifetimes, high phosphorescent efficiency and tuneableexcited states. All these characteristics make them attractive candidates for chromicdevices with applications in bioimaging, sensors and optoelectronic devices.[1]In particular, cycloplatinated complexes bearing strong field isocyanide ligands haveattracted a great interest as efficient chromophores with stimuli switching responses. Inthis regard, we have previously reported a family of chloride isocyanide Pt(II) complexeswith remarkable mechanochromic properties.[2]To expand this research, we present the synthesis of a new family of luminescent platinumcomplexes, chloride-isocyanide [Pt(C^N)Cl(CNBut)] (1) and bis-isocyanide [Pt(C^N)(CNBut)2]ClO4 (2), bearing 2-(2,4-difluorophenyl)pyridine (dfppy, a) and 4-(2-pyridyl)benzaldehyde (ppy-CHO, b) as cyclometalating ligands. The characterization andphotophysical properties of all complexes have been studied in detail and rationalizedtogether with TD-DFT calculations.The chloride derivatives exhibit an interesting multi-stimuli behaviour, related to the formation of aggregates through intermolecular Pt···Pt and/or ··· interactions, resulting in a significantly red-shifted luminescence changes that have been analysed by X-ray studies

Predictors of Response to Exclusive Enteral Nutrition in Newly Diagnosed Crohn´s Disease in Children: PRESENCE Study from SEGHNP

Exclusive enteral nutrition (EEN) has been shown to be more effective than corticosteroids in achieving mucosal healing in children with Crohn´s disease (CD) without the adverse effects of these drugs. The aims of this study were to determine the efficacy of EEN in terms of inducing clinical remission in children newly diagnosed with CD, to describe the predictive factors of response to EEN and the need for treatment with biological agents during the first 12 months of the disease. We conducted an observational retrospective multicentre study that included paediatric patients newly diagnosed with CD between 2014–2016 who underwent EEN. Two hundred and twenty-two patients (140 males) from 35 paediatric centres were included, with a mean age at diagnosis of 11.6 ± 2.5 years. The median EEN duration was 8 weeks (IQR 6.6–8.5), and 184 of the patients (83%) achieved clinical remission (weighted paediatric Crohn’s Disease activity index [wPCDAI] 15 mg/L and ileal involvement tended to respond better to EEN. EEN administered for 6–8 weeks is effective for inducing clinical remission. Due to the high response rate in our series, EEN should be used as the first-line therapy in luminal paediatric Crohn’s disease regardless of the location of disease and disease activityS

Compuestos luminiscentes cicloplatinados con propiedades multifuncionales

Los complejos plano cuadrados de platino(II) con ligandos aromáticos conjugados constituyen una nueva clase de materiales supramoleculares con interesantes propiedades espectroscópicas de gran versatilidad debido a su tendencia al apilamiento a través de interacciones metalofílicas Pt(II)-Pt(II), moduladas y, en ocasiones, asistidas por interacciones ··· entre los ligandos aromáticos. Estas propiedades se modulan con el tipo de ligandos, la carga del complejo o el microentorno, tanto en el estado fundamental como en el estado excitado. En particular, los compuestos ciclometalados de platino(II) presentan gran interés debido a sus atractivas propiedades fotofísicas con aplicaciones en diversas áreas. En este contexto, esta Tesis Doctoral se centra en la síntesis, caracterización y estudio de las propiedades de nuevos sistemas luminiscentes basados en complejos cicloplatinados(II) con ligandos isocianuro, isocianuro/acetiluro o carbenos acíclicos. Se han estudiado dos series de complejos de tipo cloro/isocianuro [Pt(C^N)Cl(CNR)] (R = Xyl y tBu) y la alquinilación de estos sustratos para obtener compuestos de tipo acetiluro/isocianuro [Pt(C^N)(CCR)(CNR)]. La variación de los ligandos isocianuro, ciclometalado (C^N) o alquinilo permite estudiar la influencia de estos ligandos en la estructura, empaquetamiento y en las propiedades fotofísicas. Este estudio, apoyado con cálculos teóricos, ha puesto de manifiesto que los compuestos con ligandos ciclometalados planos basados en la fenilpiridina exhiben una mayor tendencia a la agregación molecular a través de interacciones intermoleculares no covalentes Pt···Pt y/o ···, que gobiernan sus propiedades fotofísicas, generando simultáneamente un comportamiento mecanocrómico y emisión inducida por agregación (AIE). Con Cl/CNBut se favorecen este tipo de interacciones moleculares a largo alcance, dando lugar a materiales supramoleculares multifuncionales con propiedades vapocrómicas, solvatocrómicas, mecanocrómicas y termocrómicas. Además, el empleo de distintas rutas sintéticas ha permitido obtener separadamente isómeros cis y trans-[Pt(C^N)(CCR)(CNR)], lo que permite estudiar el efecto de la configuración cis/trans en las propiedades ópticas y su capacidad de actuar como sensores selectivos de cationes. Además, se ha preparado una familia de complejos luminiscentes de tipo carbeno acíclicos [Pt(C^N)Cl{C(NHXyl)(NHR)}] por adición nucleofílica de aminas primarias sobre el isocianuro coordinado en los precursores [Pt(C^N)Cl(CNXyl)]. Estos derivados representan los primeros ejemplos de complejos diaminocarbenos acíclicos cicloplatinados con propiedades antiproliferativas, como se ha puesto de manifiesto en los estudios de citotoxicidad e interacción del ADN realizados en colaboración con el CIBIR.Square-planar platinum(II) complexes with conjugated aromatic ligands constitute a new class of supramolecular materials with interesting spectroscopic properties of great versatility due to their tendency to stack through metallophilic Pt(II)-Pt(II) interactions, modified and, sometimes assisted, by ··· interactions between the aromatic ligands. These properties are modulated by the type of ligands, the charge of the complex and/or the microenvironment, both in the ground state and in the excited state. In particular, platinum(II) cyclometalated compounds are of great interest due to their attractive photophysical properties with applications in several areas. In this context, this PhD Thesis focuses on the synthesis, characterisation and analysis of the properties of new luminescent systems based on cycloplatinated(II) complexes bearing isocyanide, isocyanide/alkynyl or acyclic carbenes ligands. Two series of chloride/isocyanide-type complexes [Pt(C^N)Cl(CNR)] (R = Xyl and tBu) and their corresponding alkynylation process to obtain acetylide/isocyanide-type compounds [Pt(C^N)(CCR')(CNR)] have been studied. The variation of the isocyanide, cyclometalated (C^N) or alkynyl ligands has allowed us to investigate the influence of these ligands on the structure, packing and on the photophysical properties. This study, supported by theoretical calculations, has shown that compounds with planar cyclometalated ligands based on the phenylpyridinyl group exhibit a greater tendency towards molecular aggregation through non-covalent intermolecular interactions Pt···Pt and/or ···, which govern their photophysical properties, simultaneously generating mechanochromic behavior and aggregation-induced emission (AIE). These long-range molecular interactions are favoured in Cl/CNBut derivatives, resulting in multifunctional supramolecular materials with vapochromic, solvatochromic, mechanochromic and thermochromic properties. In addition, cis and trans-isomers [Pt(C^N)(CCR')(CNR)] were successfully isolated separately by using different synthetic pathways, which has allowed us to study the effect of cis/trans configuration on optical properties and their ability to act as selective cation sensors. Furthermore, a family of acyclic carbene-type luminescent complexes [Pt(C^N)Cl{C(NHXyl)(NHR)}] has been prepared by nucleophilic addition of primary amines onto the coordinated isocyanide in the precursors [Pt(C^N)Cl(CNXyl)]. These derivatives represent the first examples of cycloplatinated acyclic diaminocarbene complexes with antiproliferative properties, as evidenced by cytotoxicity and DNA interaction studies carried out in collaboration with CIBIR

Cytolocalyzation and cytotoxicity of new luminescent cyclometalated platinum(II) complexes: use as organelle biomarkers and antitumoral drugs with potential in photodynamic therapy

Two series of luminescent cyclometalated Pt(II) com-plexes were synthesized a nd their biological activitywas assessed. One was based on the deprotonated do-nor-acceptor 2-(4-dimethylaminephenyl)benzothiazoleligand (NMe 2 -pbt) and includes four mononuclear com-plexes [Pt(Me2N-pbt)(C6F5 )L] (L = Me2N-pbtH) 1, p-dpbH(4-diphenylphosphino)benzoic acid) 2, o-dpbH (2-diphe-nylphosphino)benzoic acid) [Pt(Me2N-pbt)(C6F5 )(o-dpbH)]3 (unstable), and [Pt(Me2N-pbt)(o-dpb)] 4, as well as oftwo binuclear derivatives [{Pt(Me2N-pbt)(C6F5 )}2(m-PRnP)][PR4 P = O(CH2CH2OC(O)C6H 4PPh 2)2 5; PR12P = O{(CH-2CH2O)3C(O)C6H 4PPh 2}2 6]. The second includes 2,6-di-fluorophenylpyridine (dfppy) and phenylquinoline (pq) aschromophores and acyclic diaminocarbene (ADC) ligandsas auxiliary ligands [Pt(C^N)Cl{C(NHXyl)(NHR)}] [C^N =dfppy (a), pq (b); R = Pr 7a, 8a, CH2 Ph 7b, 8b]. In theNMe2-pbt based complexes the phosphorescent emissionis lost in aerated solutions, owing to photoinduced electrontransfer to 3 O2 and formation 1 O2 singlet, as confirmed incomplexes 2 and 4. Here we report some of their biological activity. Cytotoxicity studies in the human cancer celllines A549 (lung carcinoma) and HeLa (cervix carcinoma)showed good activity for the ADC complexes 7 and 8. Tothe best of our knowledge, these compounds representthe first examples of cycloplatinated complexes bearingacyclic diamino carbenes with antiproliferative properties(Ref.). Accordingly, 7a, 7b and 8a altered DNA electropho-retic mobility pointing as a possible cytotoxic mechanism.NMe2-pbt complexes 2, 3 and 6 were also active againstA549 and HeLa cancer cells, with higher efficiency in A549,in contrast to 1, 4, and 5. Cytolocalization studies revealedthat the no cytotoxic ligand Me 2 N-pbtH and their deriva-tive complexes 1-6 exhibit specific accumulation in theGolgi apparatus. Furthermore, the potential photodynamicproperty of this type of complexes was demonstrated withthe non-cytotoxic complex 4, which demonstrated efficientphotoinduced cytotoxicity after irradiation