Design of Targeted Nanostructured Coordination Polymers (NCPs) for Cancer Therapy

Conventional cancer chemotherapy presents notable drug side effects due to non-selective action of the chemotherapeutics to normal cells. Nanoparticles decorated with receptor-specific ligands on the surface have shown an important role in improving site-selective binding, retention, and drug delivery to the cancer cells. This review summarizes the recent reported achievements using nanostructured coordination polymers (NCPs) with active targeting properties for cancer treatment in vitro and in vivo. Despite the controversy surrounding the effectivity of active targeting nanoparticles, several studies suggest that active targeting nanoparticles notably increase the selectivity and the cytotoxic effect in tumoral cells over the conventional anticancer drugs and non-targeted nanoparticle platform, which enhances drug efficacy and safety. In most cases, the nanocarriers have been endowed with remarkable capabilities such as stimuli-responsive properties, targeting abilities, or the possibility to be monitored by imaging techniques. Unfortunately, the lack of preclinical studies impedes the evaluation of these unique and promising findings for the translation of NCPs into clinical trials

Síntesis y reactividad de complejos que contienen los fragmentos Pt-S y/o Pt-H : aplicación a la reacción de desulfuración del tiofeno /

Descripció del recurs: el 19-08-2008Consultable des del TDXTítol obtingut de la portada digitalitzadaEl trabajo experimental ha desarrollado tres objetivos que se enmarcan dentro del campo de la química de coordinación del platino(II) con ligandos que contienen azufre y de sus posibles aplicaciones. Así, primero se ha profundizado en el estudio de la influencia de los ligandos terminales en la reactividad del anillo central {Pt2S2} en complejos de fórmula [Pt2L2(μ-S)2] frente a un amplio conjunto de especies electrófilas. Posteriormente, se ha explorado la reactividad del complejo [Pt2(dppp)2H3]ClO4 (dppp = Ph2P(CH2)3PPh2) en presencia de aniones sulfuro o hidrogenosulfuro bajo diferentes condiciones experimentales. Y, finalmente, se ha estudiado la reacción de dicho complejo binuclear de platino con tiofeno, reacción que se puede considerar adecuada para modelar el proceso industrial de hidrodesulfuración del petroleo, es decir, la liberación de azufre de los compuestos organosulfurados que contiene. Todos estos objetivos se han conseguido mediante la utilización de técnicas avanzadas de resolución estructural directa, RMN y espectrometría de masas, las cuales han permitido la caracterización de un elevado número de nuevos compuestos, así como el estudio de su reactividad. Además, medidas electroquímicas y cálculos computacionales (DFT) han enriquecido la caracterización de los complejos obtenidos y han permitido proponer el mecanismo que acompaña su formación. El primer objetivo se ha desarrollado mediante: a) la síntesis y caracterización estructural de [Pt2(Ph2X(CH2)2XPh2)2(µ-S)2] (X = As), b) determinación de sus propiedades redox, y c) estudio de la nucleofilicidad de los átomos de azufre respecto a diversos centros metálicos, ácidos próticos (HCl, HClO4) y electrófilos orgánicos (CH2Cl2). La comparación de estos resultados con los anteriormente obtenidos para X = P ha permitido concluir que el cambio de átomo donador X en los ligandos terminales del anillo central {Pt2S2} no implica cambios estructurales notables entre complejos análogos, pero en cambio X = As provoca una disminución en la densidad electrónica de los aniones sulfuro y una considerable variación en las cinéticas de reacción. El segundo objetivo se ha analizado mediante el estudio pormenorizado de la reacción del complejo trihidruro de platino(II) [Pt2(dppp)2H3]ClO4] (dppp = Ph2P(CH2)3PPh2) con reactivos sulfurados sencillos (NaSH y Na2S) bajo diferentes condiciones experimentales. El seguimiento de estas reacciones ha permitido caracterizar por primera vez diversos complejos de Pt(II) que contienen fragmentos Pt-H, Pt-SH y/o Pt-S. Un análisis posterior ha evidenciado la fácil interconversión entre los compuestos obtenidos, transformación que transcurre por diferentes caminos según las condiciones de reacción utilizadas. Esta reactividad informa sobre las posibles transformaciones químicas que pueden tener lugar en la superficie de un catalizador heterogéneo en el proceso industrial de hidrodesulfuración. El tercer objetivo ha implicado el estudio de la reacción del complejo trihidruro dinuclear de platino [Pt2(dppp)2H3]ClO4 con tiofeno en diferentes condiciones experimentales. Así, la activación del enlace C-S del tiofeno por parte del complejo [Pt2(dppp)2H3]ClO4 ha dado lugar al metalaciclo mononuclear [Pt(dppp)(SC4H4-C,S)], que implica exclusivamente la activación de un enlace C-S tiofénico, y al complejo dinuclear [Pt2(dppp)2(μ SC4H5-C,S)]ClO4, en donde la activación del enlace C-S va acompañada de la hidrogenación parcial del tiofeno. Experimentos adicionales y cálculos computacionales han evidenciado el papel del tiofeno como promotor de la ruptura del complejo trihidruro dinuclear de platino. También han evidenciado que los dos complejos de platino obtenidos no se interconvierten entre sí, y por tanto su formación transcurre mediante dos mecanismos en paralelo. En conclusión, la combinación de estudios experimentales y teóricos referidos a la reacción de [Pt2(dppp)2H3]ClO4 con tiofeno ha proporcionado una nueva perspectiva en el estudio del mecanismo HDS en fase homogénea.The experimental work has aimed at three objectives, all embodied in the field of the coordination chemistry of Pt(II) with sulfur-containing ligands and their possible applications. Thus, firstly, the influence of the terminal ligands in the reactivity of the central {Pt2S2} ring in complexes of formula [Pt2L2(μ-S)2] towards a wide collection of electrophilic species has been thoroughly studied. Subsequently, the reactivity of the complex [Pt2(dppp)2H3]ClO4 (dppp = Ph2P(CH2)3PPh2) in the presence of sulfide or hydrogensulfide anions has been explored under various experimental conditions. And finally, the reaction of the upper binuclear platinum complex with thiophene has been analyzed in detail. This reaction can be considered as a good model for the industrial process of hydrodesulfurization of petroleum, which involves the removal of sulfur from the included organosulfur compounds. All of these objectives have been achieved using advanced techniques of direct structural resolution, NMR and mass spectrometry, which have allowed the characterization of a high number of new complexes, as well as the study of its reactivity. In addition, electrochemistry measurements and in silico studies (DFT) have enriched the characterization of the complexes obtained and they have also allowed us to propose the reaction mechanism that accompanies their formation. The first objective has been developed through: a) the synthesis and structural characterization of [Pt2(Ph2X(CH2)2XPh2)2(µ-S)2] (X = As), b) the determination of its redox properties, and c) the study of the nucleophilicity of the sulfur atoms towards various metal centres, protic acids (HCl, HClO4) and organic electrophiles (CH2Cl2). Comparison of these results with those previously obtained for X = P have allowed us to conclude that the replacement of the donor atom X in the terminal ligands bound to the {Pt2S2} core does not involve significant structural changes in analogue complexes. However, when X = As the electronic density of the bridging sulfur atoms decrease and the corresponding reaction kinetics undergo considerable variations. The second objective has been analysed by means of a detailed study of the reaction between the trihydride platinum(II) complex [Pt2(dppp)2H3]ClO4] (dppp = Ph2P(CH2)3PPh2) and simple sulfur-containg species (NaSH or Na2S) under different experimental conditions. The monitoring of these reactions has led us to the unprecedented characterization of various Pt(II) complexes that include Pt-H, Pt-SH and/or Pt-S fragments. Subsequent studies have evidenced the ease of interconversion between the complexes obtained, which occurs through different pathways depending on the reaction conditions used. This reactivity gives information about the possible chemical transformations that can take place in the surface of the heterogeneous catalyst in the industrial process of hydrodesulfurization. The third objective has involved the reaction study of the binuclear trihydride platinum complex [Pt2(dppp)2H3]ClO4 with thiophene under different experimental conditions. Thus, C-S bond activation of thiophene by [Pt2(dppp)2H3]ClO4 has afforded the mononuclear [Pt(dppp)(SC4H4-C,S)] metallacycle that involves activation of the thiophenic C-S bond exclusively, and the dinuclear [Pt2(dppp)2(μ SC4H5-C,S)]ClO4 complex, where activation of this bond is concomitant with the partial hydrogenation of thiophene. Additional experiments and computational results have evidenced the role of thiophene as promoter of the cleavage of the binuclear platinum complex. They have also showed the non interconversion equilibrium between the two new platinum complexes obtained, thus indicating that two concurrent mechanisms are at work. Overall, the combination of experimental and theoretical studies of the reaction of [Pt2(dppp)2H3]ClO4 with thiophene has provided new insights into the mechanism of the homogeneous HDS

Coordination polymers built from 1,4-bis(imidazol-1-ylmethyl)benzene : from crystalline to amorphous

The supramolecular chemistry of the bis-imidazole ligand 1,4-bis(imidazol-1-ylmethyl)benzene, popularly known as bix, has been explored by various researchers in order to synthesize functional coordination polymers (CPs). The flexibility of the bix ligand, its unpredictable conformation and its coordination behaviour with transition metal ions have resulted in a huge number of structurally diverse and functionally intriguing CPs. In this perspective review we discuss the progress in CPs of bix between 1997 and today. More precisely, this review emphasizes the developments in functional supramolecular coordination polymers built from the bix ligand, from crystalline materials to amorphous nanomaterials

Nous agents de contrast en IRM per al diagnòstic de tumors cerebrals

Investigadores de la UAB y del Institut Català de Nanociència I Nanotecnologia (ICN2) han desarrollado una partícula a base de polímeros de coordinación a nanoescala (NCP) construida con iones metálicos de hierro(III) paramagnético capaces de mostrar un alto contraste en T1 y T2 para la Imagen por Resonancia magnética (IRM) in vivo, permitiendo la obtención simultánea de imágenes de contraste positivo y negativo en un período de tiempo muy corto. Este trabajo abre nuevas posibilidades en la obtención de nanopartículas fácilmente biodegradables y no tóxicas con mejores propiedades como agentes de contraste duales T1 / T2 en IRM para el diagnóstico de tumores.Investigadors de la UAB i de l'Institut Català de Nanociència I Nanotecnologia (ICN2) han desenvolupat una partícula a base de polímers de coordinació a nanoescala (NCP) construïda amb ions metàl·lics de ferro(III) paramagnètic capaços de mostrar un alt contrast en T1 i T2 per a la Imatge per Ressonància magnètica (IRM) in vivo, permetent l'obtenció simultània d'imatges de contrast positiu i negatiu en un període de temps molt curt. Aquest treball obre noves possibilitats en l'obtenció de nanopartícules fàcilment biodegradables i no tòxics amb millors propietats com a agents de contrast duals T1 / T2 a IRM per al diagnòstic de tumors.Researchers from the UAB and the Institut Català de Nanociència I Nanotecnologia (ICN2) have developed a nanoscale coordination polymer particle (NCP) built using paramagnetic iron(III) metal ions able to exhibit T1 and T2 high contrast potential for the magnetic resonance image (MRI) in vivo, allowing simultaneous recording of positive and negative contrast images in a very short period of time. This work opens new possibilities in constructing easily biodegradable and nontoxic nanoparticles with improved T1/T2 dual-mode MRI contrast enhancement for tumour diagnosis

Water-Stable Upconverting Coordination Polymer Nanoparticles for Transparent Films and Anticounterfeiting Patterns with Air-Stable Upconversion

Altres ajuts: acords transformatius de la UABPhoton upconversion (UC) based on triplet-triplet annihilation is a very promising phenomenon with potential application in several areas, though, due to the intrinsic mechanism, the achievement of diffusion-limited solid materials with air-stable UC is still a challenge. Herein, we report UC coordination polymer nanoparticles (CPNs) combining sensitizer and emitter molecules especially designed with alkyl spacers that promote the amorphous character. Beyond the characteristic constraints of crystalline MOFs, amorphous CPNs facilitate high dye density and flexible ratio tunability. To show the universality of the approach, two types of UC-CPNs are reported, exhibiting highly photostable UC in two different visible spectral regions. Given their nanoscale, narrow size distribution, and good chemical/colloidal stability in water, the CPNs were also successfully printed as anticounterfeiting patterns and used to make highly transparent and photostable films for luminescent solar concentrators, both showing air-stable UC

Coordination Polymer Particles with ligand-centred pH-responses and spin transition

A bis-catechol ligand connected through an imine bond is used to fabricate switchable coordination polymer particles with pH-tuned spin transition responses

Switchable colloids, thin-films and interphases based on metal complexes with non-innocent ligands: the case of valence tautomerism and their applications

Successful nanostructuration approaches developed in the last few years have allowed the preparation of robust valence tautomeric (VT) switchable (micro-/nano-) structures of a variety of dimensions and morphologies. These results are expected to definitely foster the implementation of these materials on hybrid molecular electronic devices but also endorse new applications in other different fields such as sensing, drug delivery or water remediation, among others.N. A. V.-M. thanks the Ministerio de Ciencia e Innovación (MICINN) for a predoctoral FPU fellowship. M. G. thanks the CSIC for a predoctoral grant (JAEpre). C. B. thanks the ICN2 and the Severo Ochoa program for his predoctoral grant. This work was supported by projects MAT2015-70615-R and CTQ2015-65439-R from the Spanish Government and by FEDER funds. ICN2 acknowledges support from the Severo Ochoa Program (MINECO, Grant SEV-2013-0295).We acknowledge support by the CSIC Open Access Publication Initiative through its Unit of Information Resources for Research (URICI).Peer Reviewe

Coordination polymer nanoparticles in medicine

Coordination polymer particles (CPPs) have recently emerged as a new family of nanoparticles. The potential multifunctionality of these nanosystems and the flexibility of their coordination chemistry open new perspectives in different fields, including medicine. This review outlines the most recent advances in this field, from CPP synthesis to their use as smart drug delivery systems, bioimaging probes or a combination of both

Surface Functionalization of Metal-Organic Framework Crystals with Catechol Coatings for Enhanced Moisture Tolerance

Robust catechol coatings for enhanced moisture tolerance were produced in one step by direct reaction of Hong Kong University of Science and Technology (HKUST) with synthetic catechols. We ascribe the rapid formation of homogeneous coatings around the metal-organic framework particles to the biomimetic catalytic activity of Cu(II) dimers in the external surface of the crystals. Use of fluorinated catechols results in hydrophobic, permeable coatings that protect HKUST from water degradation while retaining close to 100% of its original sorption capacity

Design and Synthesis of a Noninnocent Multitopic Catechol and Pyridine Mixed Ligand : Nanoscale Polymers and Valence Tautomerism

The design and synthesis of a new redox-active ligand combining catechol and pyridine units have allowed the achievement of cobalt-based nanoscale coordination polymer particles in a single-step exhibiting a switchable valence tautomeric behavior and thermal hysteresis. The combination of polymerizing capabilities with redox-active responses in a unique ligand leads to the formation of nanoparticles exhibiting a gradual valence tautomeric interconversion in the 35-370 K temperature range. Using one single ligand to obtain these nanoparticles facilitates possible nanostructure formation methodologies. (Chemical Equation Presented)