Negatively charged metallacarborane redox couples with both members stable to air

It was possible to synthesize and isolate redox couples in which both partners are negatively charged. The handy framework is [3,3'-Co(1,2-closo-C2B9H11)2]-. The E½ potential can be tuned by adjusting the nature and number of substituents on B and C. The octaiodinated species [3,3'-Co(1,2-closo-C2B9H7I4)2]- is the most favorable as it is isolatable and stable in air

Ion Transport across Biological Membranes by Carborane-Capped Gold Nanoparticles

Carborane-capped gold nanoparticles (Au/carborane NPs, 2-3 nm) can act as artificial ion transporters across biological membranes. The particles themselves are large hydrophobic anions that have the ability to disperse in aqueous media and to partition over both sides of a phospholipid bilayer membrane. Their presence therefore causes a membrane potential that is determined by the relative concentrations of particles on each side of the membrane according to the Nernst equation. The particles tend to adsorb to both sides of the membrane and can flip across if changes in membrane potential require their repartitioning. Such changes can be made either with a potentiostat in an electrochemical cell or by competition with another partitioning ion, for example, potassium in the presence of its specific transporter valinomycin. Carborane-capped gold nanoparticles have a ligand shell full of voids, which stem from the packing of near spherical ligands on a near spherical metal core. These voids are normally filled with sodium or potassium ions, and the charge is overcompensated by excess electrons in the metal core. The anionic particles are therefore able to take up and release a certain payload of cations and to adjust their net charge accordingly. It is demonstrated by potential-dependent fluorescence spectroscopy that polarized phospholipid membranes of vesicles can be depolarized by ion transport mediated by the particles. It is also shown that the particles act as alkali-ion-specific transporters across free-standing membranes under potentiostatic control. Magnesium ions are not transported

On the verge of bioorganic and inorganic chemistry: metallacarboranes in nanomedicine

La investigación presentada en esta tesis describe la síntesis y caracterización de derivados aniónicos de metalacarboranos y las aplicaciones posteriores. La primera sección de la tesis se centra en la síntesis y caracterización de derivados metilados del cobaltacarboranos. La reacción de alquilación se ha logrado con éxito mediante acoplamiento cruzado entre el vértice BI y un reactivo de Grignard en presencia de [PdCl2(PPh3)2] como catalizador y CuI como cocatalizador. La determinación y la modulación del potencial redox de metalacarboranos con diferentes sustituientes ha sido estudiado con gran interés en nuestro grupo. Por lo tanto, se ha desarrollado con éxito una ruta sintética eficiente para obtener derivados clorados de metalacarboranos y el posterior estudio de las propiedades electroquímicas de los compuestos que se han sintetizado. El E1/2 (MIII/MII, M=Co, Fe) de los aniones B-halogenado y B-metilado de los metalacarboranos que se determinaron experimentalmente por voltametría cíclica indican que cada halógeno (Cl o I) introducido produce un efecto mayor y contrario al que produce el grupo alquilo. Basándose en su E1/2 potencial, ciertos compuestos seleccionados han sido probados como electrolitos en los dispositivos DSSC. Un logro importante reportado en esta tesis fue el aislamiento de diferentes sales de calcio, plata y hierro del cobaltacarboranos [3]- y sus derivados yodados. La posible aplicación de moléculas aniónicas altamente yodadas como agentes de contraste radiopacos para diagnóstico mediante imágenes de rayos X, requiere la síntesis y caracterización de Ca[I4-3]2 y Ca[I8-3]2. Las sales de plata derivadas del cobaltacarborano se han utilizado como precursoras para preparar las correspondientes sales de Fe(II) y Fe(III) que pueden formar nanopartículas magnéticas. La capacidad de los metalocarboranos individuales para el autoensamblaje y el agregado en soluciones acuosas se ha estudiado en los últimos años. Más recientemente, se ha demostrado que pequeños cambios en la estructura molecular de [3]- provocan modificaciones importantes en su comportamiento en disolución. Cuando se trabaja a altas concentraciones, la sustitución de dos BH por dos BI en la estructura de [3]- conduce a una fase liotrópica lamelar, mientras que las vesículas se forman a concentraciones bajas (1-9mM). Hemos preparado, aislado y caracterizado diferentes sales de cobaltacarborano y algunos derivados para los cuales se ha estudiado su comportamiento en D2O a diferentas concentraciones mediante 1H{11B}-RMN y 11B{1H}-RMN. Otro objetivo importante fue la reacción de apertura de anillo de los derivados de metalacarboranos functionalizados con un anillo de dioxano con biomoléculas, tales como vitaminas, ácidos grasos y azúcares a través de una reacción nucleófila. La reacción de yodación de estas biomoléculas con I2 natural, se realizó con éxito y con buenos rendimientos. Hemos diseñado nuevos derivados bioactivos de metalacarboranos que contienen dos posiciones reactivas diferentes: un átomo yodado para ser radiomarcado y una rama de PEG que se une al vector biológico. Las soluciones inyectables de compuestos química y radioquímicamente puras se han obtenido después de las reacciones de radiomarcaje, ya sea con 125I o 124I a través de la reacción de intercambio isotópico empleando un complejo de paladio como catalizador. Posteriormente se han realizado estudios de biodistribucion in vivo mediante Tomografía por Emisión de Positrones (PET) en ratones sanos y una vez confirmada la bioacumulation se estudió para ratones con cáncer de páncreas y pulmón.The research presented in this thesis describes the synthesis and characterization of anionic metallabis(dicarbollide) derivatives and the posterior applications. The first section of the thesis is focused on the synthesis and characterization of methylated cobaltabis(dicarbollide) derivatives. The alkylation reaction has been successfully accomplished by cross-coupling reaction between the B-I vertex and Grignard reagent in the presence of [PdCl2(PPh3)2] as catalyst and CuI as cocatalyst. The redox potential determination and modulation of differently substituted metallacarboranes is a matter of interest in our group. So, an efficient synthetic pathway to obtain chlorinated metallabis(dicarbollide) derivatives has been successfully developed and the posterior study of electrochemical properties of the compounds has been accomplished. The E1/2 (MIII/MII, M=Co, Fe) for B-halogenated and B-methylated metallabis(dicarbollide) anions were experimentally determined by Cyclic Voltammetry indicating that each halogen atom (Cl or I) produces an opposite and larger effect than each alkyl moiety. Based on their E1/2 potential, selected compounds have been tested as electrolytes in the DSSC devices. An important achievement reported in this thesis was the isolation of different calcium, silver and iron salts of cobaltabis(dicarbollide) [3]- and its iodinated derivatives. The possible application of such highly iodinated anionic molecules as radiopaque contrast agent for X-ray diagnosting imaging, required the synthesis and characterization of Ca[I4-3]2 and Ca[I8-3]2. Silver set of cobaltabis(dicarbollide) derivatives have been used as precursor to prepare the corresponding Fe(II) and Fe(III) salts that can form magnetic nanoparticles. The ability of single metallacarboranes to self-assembly and aggregate in aqueous solutions has been demonstrated in the last few years. More recently, it has been proven that minor changes in the molecular structure of [3]- provoke major modifications in the solution behavior. The substitution of two B-H by two B-I in the structure of [3]- leads to a lamellae lyotropic phase at high concentration, while vesicles are formed at small concentration (1-9mM). We prepared, isolated and characterized a set of different salts of the parent cobaltabis(dicarbollide) and some of its derivatives and we studied by 1H{11B}-NMR and 11B{1H}-NMR in D2O their behavior at different concentrations. Another important goal was the ring opening reaction of the zwitterionic metallabis(dicarbollide) derivatives with biomolecules, such as vitamins, fatty acids and sugars via a nucleophilic reaction. The iodination reaction of this biomolecules with natural I2 was successfully performed in good yields. We have designed new bio-functional metallabis(dicarbollide) derivatives which contain two different reactive sites: a suitable iodinated moiety ready to be radiolabeled and a PEG branch that can carry the vector. Injectable solutions of chemically and radiochemically pure compounds have been obtained after the radiolabelling reactions with either 125I or 124I via palladium catalyzed isotopic exchange reaction. In vivo Positron Emission Tomography (PET) biodistribution studies were performed on healthy mice and also in tumor model

On the verge of bioorganic and inorganic chemistry : metallacarboranes in nanomedicine /

La investigación presentada en esta tesis describe la síntesis y caracterización de derivados aniónicos de metalacarboranos y las aplicaciones posteriores. La primera sección de la tesis se centra en la síntesis y caracterización de derivados metilados del cobaltacarboranos. La reacción de alquilación se ha logrado con éxito mediante acoplamiento cruzado entre el vértice BI y un reactivo de Grignard en presencia de [PdCl2(PPh3)2] como catalizador y CuI como cocatalizador. La determinación y la modulación del potencial redox de metalacarboranos con diferentes sustituientes ha sido estudiado con gran interés en nuestro grupo. Por lo tanto, se ha desarrollado con éxito una ruta sintética eficiente para obtener derivados clorados de metalacarboranos y el posterior estudio de las propiedades electroquímicas de los compuestos que se han sintetizado. El E1/2 (MIII/MII, M=Co, Fe) de los aniones B-halogenado y B-metilado de los metalacarboranos que se determinaron experimentalmente por voltametría cíclica indican que cada halógeno (Cl o I) introducido produce un efecto mayor y contrario al que produce el grupo alquilo. Basándose en su E1/2 potencial, ciertos compuestos seleccionados han sido probados como electrolitos en los dispositivos DSSC. Un logro importante reportado en esta tesis fue el aislamiento de diferentes sales de calcio, plata y hierro del cobaltacarboranos [3]- y sus derivados yodados. La posible aplicación de moléculas aniónicas altamente yodadas como agentes de contraste radiopacos para diagnóstico mediante imágenes de rayos X, requiere la síntesis y caracterización de Ca[I4-3]2 y Ca[I8-3]2. Las sales de plata derivadas del cobaltacarborano se han utilizado como precursoras para preparar las correspondientes sales de Fe(II) y Fe(III) que pueden formar nanopartículas magnéticas. La capacidad de los metalocarboranos individuales para el autoensamblaje y el agregado en soluciones acuosas se ha estudiado en los últimos años. Más recientemente, se ha demostrado que pequeños cambios en la estructura molecular de [3]- provocan modificaciones importantes en su comportamiento en disolución. Cuando se trabaja a altas concentraciones, la sustitución de dos BH por dos BI en la estructura de [3]- conduce a una fase liotrópica lamelar, mientras que las vesículas se forman a concentraciones bajas (1-9mM). Hemos preparado, aislado y caracterizado diferentes sales de cobaltacarborano y algunos derivados para los cuales se ha estudiado su comportamiento en D2O a diferentas concentraciones mediante 1H{11B}-RMN y 11B{1H}-RMN. Otro objetivo importante fue la reacción de apertura de anillo de los derivados de metalacarboranos functionalizados con un anillo de dioxano con biomoléculas, tales como vitaminas, ácidos grasos y azúcares a través de una reacción nucleófila. La reacción de yodación de estas biomoléculas con I2 natural, se realizó con éxito y con buenos rendimientos. Hemos diseñado nuevos derivados bioactivos de metalacarboranos que contienen dos posiciones reactivas diferentes: un átomo yodado para ser radiomarcado y una rama de PEG que se une al vector biológico. Las soluciones inyectables de compuestos química y radioquímicamente puras se han obtenido después de las reacciones de radiomarcaje, ya sea con 125I o 124I a través de la reacción de intercambio isotópico empleando un complejo de paladio como catalizador. Posteriormente se han realizado estudios de biodistribucion in vivo mediante Tomografía por Emisión de Positrones (PET) en ratones sanos y una vez confirmada la bioacumulation se estudió para ratones con cáncer de páncreas y pulmón.The research presented in this thesis describes the synthesis and characterization of anionic metallabis(dicarbollide) derivatives and the posterior applications. The first section of the thesis is focused on the synthesis and characterization of methylated cobaltabis(dicarbollide) derivatives. The alkylation reaction has been successfully accomplished by cross-coupling reaction between the B-I vertex and Grignard reagent in the presence of [PdCl2(PPh3)2] as catalyst and CuI as cocatalyst. The redox potential determination and modulation of differently substituted metallacarboranes is a matter of interest in our group. So, an efficient synthetic pathway to obtain chlorinated metallabis(dicarbollide) derivatives has been successfully developed and the posterior study of electrochemical properties of the compounds has been accomplished. The E1/2 (MIII/MII, M=Co, Fe) for B-halogenated and B-methylated metallabis(dicarbollide) anions were experimentally determined by Cyclic Voltammetry indicating that each halogen atom (Cl or I) produces an opposite and larger effect than each alkyl moiety. Based on their E1/2 potential, selected compounds have been tested as electrolytes in the DSSC devices. An important achievement reported in this thesis was the isolation of different calcium, silver and iron salts of cobaltabis(dicarbollide) [3]- and its iodinated derivatives. The possible application of such highly iodinated anionic molecules as radiopaque contrast agent for X-ray diagnosting imaging, required the synthesis and characterization of Ca[I4-3]2 and Ca[I8-3]2. Silver set of cobaltabis(dicarbollide) derivatives have been used as precursor to prepare the corresponding Fe(II) and Fe(III) salts that can form magnetic nanoparticles. The ability of single metallacarboranes to self-assembly and aggregate in aqueous solutions has been demonstrated in the last few years. More recently, it has been proven that minor changes in the molecular structure of [3]- provoke major modifications in the solution behavior. The substitution of two B-H by two B-I in the structure of [3]- leads to a lamellae lyotropic phase at high concentration, while vesicles are formed at small concentration (1-9mM). We prepared, isolated and characterized a set of different salts of the parent cobaltabis(dicarbollide) and some of its derivatives and we studied by 1H{11B}-NMR and 11B{1H}-NMR in D2O their behavior at different concentrations. Another important goal was the ring opening reaction of the zwitterionic metallabis(dicarbollide) derivatives with biomolecules, such as vitamins, fatty acids and sugars via a nucleophilic reaction. The iodination reaction of this biomolecules with natural I2 was successfully performed in good yields. We have designed new bio-functional metallabis(dicarbollide) derivatives which contain two different reactive sites: a suitable iodinated moiety ready to be radiolabeled and a PEG branch that can carry the vector. Injectable solutions of chemically and radiochemically pure compounds have been obtained after the radiolabelling reactions with either 125I or 124I via palladium catalyzed isotopic exchange reaction. In vivo Positron Emission Tomography (PET) biodistribution studies were performed on healthy mice and also in tumor model

Towards purely inorganic clusters in medicine : biocompatible divalent cations as counterions of cobaltabis(dicarbollide) and its iodinated derivatives

Monovalent cations, Cs+, and alkylammonium ([NR4]+) salts have traditionally been used to precipitate the anions of boranes, carborane and metallocarborane clusters. In contrast, in the body and in living organisms in general, divalent cations have a special relevance. In this work, we isolate for the first time the cobaltabis(dicarbollide) salts of the biocompatible divalent cations of biological importance that can have application both in biology and in materials science. The preparation of Ca2+, Mg2+ and Fe2+ salts of anionic iodinated nido-[C2B9H12]− and cobaltabis(dicarbollide) as well as its di-, tetra- and octa-iodinated derivatives are reported. Ca2+ and Mg2+ are hard Lewis acids and thus forms aqua ions if water is present in the synthetic process. All solid Ca2+ and Mg2+ salts studied in this work contained water molecules coordinated that have been detected by IR and TGA/DSC. Fe2+ is a medium hard Lewis acid and Fe3+ is a hard one. In acetone they do not coordinate to cobaltabis(dicarbollide) anion, but are solvated by acetone. The studied Ca2+ salts of iodinated cobaltabis(dicarbollide) are basically inorganic small molecules that provide at once the biocompatible divalent Ca2+ cation and and iodinated anions thus simultaneously providing an X-ray contrast agent and/or bone defect repairing agent in regenerative medicine.peerReviewe

A fast and simple B–C bond formation in metallacarboranes avoiding halometallacarboranes and transition metal catalysts†

An electrophilic substitution on metallacarboranes by using a stabilized carbocation that can be made in situ is reported for the first time. This new synthetic methodology provides a new perspective on easy metallacarborane derivatization with organic fragments, which enhances the properties of both fragments and widens their possible applications.This work has been supported by the Spanish Ministerio de Economía y Competitividad (CTQ2016-75150-R), the Generalitat de Catalunya (2017SGR1720) and European Union’s Horizon 2020 Marie Skłodowska-Curie grant agreement MSCA-IF-2016-751587. A. B. Buades is enrolled in the PhD program of UAB.Peer reviewe

Towards purely inorganic clusters in medicine: Biocompatible divalent cations as counterions of cobaltabis(dicarbollide) and its iodinated derivatives

Monovalent cations, Cs+, and alkylammonium ([NR4]+) salts have traditionally been used to precipitate the anions of boranes, carborane and metallocarborane clusters. In contrast, in the body and in living organisms in general, divalent cations have a special relevance. In this work, we isolate for the first time the cobaltabis(dicarbollide) salts of the biocompatible divalent cations of biological importance that can have application both in biology and in materials science. The preparation of Ca2+, Mg2+ and Fe2+ salts of anionic iodinated nido-[C2B9H12]− and cobaltabis(dicarbollide) as well as its di-, tetra- and octa-iodinated derivatives are reported. Ca2+ and Mg2+ are hard Lewis acids and thus forms aqua ions if water is present in the synthetic process. All solid Ca2+ and Mg2+ salts studied in this work contained water molecules coordinated that have been detected by IR and TGA/DSC. Fe2+ is a medium hard Lewis acid and Fe3+ is a hard one. In acetone they do not coordinate to cobaltabis(dicarbollide) anion, but are solvated by acetone. The studied Ca2+ salts of iodinated cobaltabis(dicarbollide) are basically inorganic small molecules that provide at once the biocompatible divalent Ca2+ cation and and iodinated anions thus simultaneously providing an X-ray contrast agent and/or bone defect repairing agent in regenerative medicine.This work has been supported by the Spanish Ministerio de Economía y Competitividad (CTQ2016-75150-R) and the Generalitat de Catalunya (2017SGR1720). Miquel Nuez is enrolled in the PhD program of the UAB.Peer reviewe

How to get the desired reduction voltage in a single framework! Metallacarborane as an optimal probe for sequential voltage tuning

An appealingly wide set of redox couples ranging from -1.74 to -0.35 V based on a metallabisdicarbollide derivative, [M(C2B9H11-yIy)2]- (M = Co, Fe), each being distinguished from the former by near 0.15 V and all having the same structure have been demonstrated. The redox active methyl viologen moiety ([MV]2+) has been used as a benchmark

Deciphering the role of the cation in anionic cobaltabisdicarbollide clusters

International audienceThe counter cation influence (H+, Na+, K+ and Li+) on the aggregates formation in aqueous solution of the salts of cobaltabisdicarbollide [1]- and its derivatives (monoiodinated [I-1]- and diiodinated [I2-1]-) has been studied by means of 11B{1H} and 1H{11B} NMR spectroscopy. 11B{1H} NMR spectrum of M[1] (M= alkali or H+) in water exhibits much wider signals than in an organic solvent because organic solvents (acetone) cause disaggregation. The wider resonances are found at concentrations larger than 10 mM while the sharpest signals are found below 10 mM, in which a large fraction of H[1] is in monomeric form and only a small fraction of H[1] participate in the formation of vesicles that has been visualized by CryoTEM. 11B{1H} NMR of H[1] at concentrations lower than 10 mM corresponds to the monomer and the phase transition that is observed is due to the monomer to micelles transformation. The 11B-NMR is, therefore, an excellent probe to visualize the phase transition between vesicles/monomer and micelles/monomer that appears between 10 and 20mM, for all tested cations. The 1H{11B} NMR spectra contribute interesting complementary information to the one retrieved from the 11B{1H} NMR, particularly in what concerns to dihydrogen bonds formation, C-H···H-B. These results have been compared with available crystal structures, which reveal the presence of such intermolecular dihydrogen bonds as responsible of the aggregates formation of [1]- in water. Computational analysis of the intermolecular interactions and self-assembly of the anions [1]- [I2-1]- are presented

Graphene Modified Fluorinated Cation-Exchange Membranes for Proton Exchange Membrane Water Electrolysis

One of major current technical challenges in proton exchange membrane water electrolysis (PEMWE) is the limited proton conductivity. Nowadays, graphene is considered one of the most promising candidates for improving the ionic transport properties, isotopic selectivity and proton conductivity throughout the unique two-dimensional structure. In this paper, we report on the development of graphene modified commercial membranes (Fumapem®) containing different graphene loadings for PEMWE applications. The membranes are characterized by Scanning Electron Microscopy (SEM) and thermo-gravimetrical and differential thermal analysis (TGA-DSC). Properties of composite membranes are investigated, including water uptake and ion-exchange capacity (IEC). In plane four-electrode arrangement is used to determine the proton conductivity of the composite membranes. It is found that composite membranes show an improved behaviour when compared to pristine commercial membranes and graphene loading can improve proton conductivity. In our conditions, the calculated activation energy (Ea) for proton conduction is found to be about 3.80 kJ mol−1 for the composite Fumapem®/graphene membrane with 10 mg graphene loading, lower than of the pristine polymer proton exchange membrane