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

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.This work was supported by the project MAT2012-38318-C03-02 from the Spanish Government and FEDER funds. F. N. thanks Universidad Nacional del Sur for supporting her postdoctoral stay. F. N. thanks the Ministerio de Ciencia e Innovación (MICINN) for a postdoctoral JdC fellowship. The authors also thank ECOSTBio Cost Action.Peer Reviewe

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

Covalent Grafting of Coordination Polymers on Surfaces: The Case of Hybrid Valence Tautomeric Interphases

© 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim. We have developed a novel approach for grafting coordination polymers, structured as nanoparticles bearing surface reactive carboxylic groups, to amino-functionalized surfaces through a simple carbodiimide-mediated coupling reaction. As a proof-of-concept to validate our approach, and on the quest for novel hybrid interphases with potential technological applications, we have used valence tautomeric nanoparticles exhibiting spin transition at or around room temperature. SEM and AFM characterization reveal that the nanoparticles were organized chiefly into a single monolayer while X-ray photoelectron spectroscopy (XPS) measurements confirm that the nanoparticles retain a temperature-induced electronic redistribution upon surface anchorage. Our results represent an effective approach towards the challenging manufacture of coordination polymers. CPPs immobilization: A generic approach for immobilizing coordination polymer nanoparticles (CPPs) on gold surfaces is reported. The protocol involves covalent bonding between amino-terminated alkyl chains on the gold surface and carboxylic groups on the CPPs surface. The thickness of the nanoparticle monolayer is comparable to the nanoparticle size. The nanoparticles used exhibit valence tautomerism in bulk and keep this property after surface attachment, as corroborated by X-ray photoelectron spectroscopy (XPS) measurements. The results represent an effective approach towards the manufacture of coordination polymers.F. N. thanks the Ministerio de Ciencia e Innovación (MICINN) for a postdoctoral JdC fellowship. This work was supported by project MAT2012-38318-C03-02 from the Spanish Government and by FEDER funds. ICN2 acknowledges support from the Severo Ochoa Program (MINECO, Grant SEV-2013-0295). The authors also thank MP1202 Cost ActionPeer Reviewe

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

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.This work was supported ICN2 acknowledges support from the Severo Ochoa Program (MINECO, Grant SEV-2013-0295). F.N. thanks the Ministerio de Ciencia e Innovación (MICINN) for a JdC fellowship. M.G. thanks the Consejo Superior de Investigaciones Cientifícas (CSIC) for a JAE fellowship.Peer Reviewe

Carboxyl group (-CO2H) functionalized coordination polymer nanoparticles as efficient platforms for drug delivery

Functionalization of nanoparticles can significantly influence their properties and potential applications. Although researchers can now functionalize metal, metal oxide, and organic polymer nanoparticles with a high degree of precision, controlled surface functionalization of nanoscale coordination polymer particles (CPPs) has remained a significant challenge. The lack of methodology is perhaps one of the greatest roadblocks to the advancement of CPPs into high added-value drug delivery applications. Here, we report having achieved this goal through a stepwise formation and functionalization protocol. We fabricated robust nanoparticles with enhanced thermal and colloidal stabilities by incorporation of carboxyl groups and these surface carboxyl groups could be subsequently functionalized through well-known peptide coupling reactions. The set of chemistries that we employed as proof-of-concept enabled a plethora of new functional improvements for the application of CPPs as drug delivery carriers, including enhanced colloidal stabilities and the incorporation of additional functional groups such as polyethylene glycol (PEG) or fluorescent dyes that enabled tracking of their cellular uptake. Finally, we ascertained the cytotoxicity of the new CPP nanoparticles loaded with camptothecin to human breast adenocarcinoma (MCF-7). Efflux measurements show that the encapsulation of camptothecin enhances the potency of the drug 6.5-fold and increases the drug retention within the cell.We acknowledge the financial support of the Ministerio de Economía y Competitividad through project MAT2012–38318-C03–02. F.N. thanks the Ministerio de Economía y Competitividad (MINECO) for a JdC (JCI-2011–09239) post-doctoral grant. F.N. also thanks the Universidad Nacional del Sur for financial support. Thanks to COST Action MP1106 and TD1004.Peer Reviewe

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