Cobaltabis(dicarbollide) ([o-COSAN]−) as Multifunctional Chemotherapeutics: A Prospective Application in Boron Neutron Capture Therapy (BNCT) for Glioblastoma

Purpose: The aim of our study was to assess if the sodium salt of cobaltabis(dicarbollide) and its di-iodinated derivative (Na[o-COSAN] and Na[8,8′-I2-o-COSAN]) could be promising agents for dual anti-cancer treatment (chemotherapy + BNCT) for GBM. Methods: The biological activities of the small molecules were evaluated in vitro with glioblastoma cells lines U87 and T98G in 2D and 3D cell models and in vivo in the small model animal Caenorhabditis elegans (C. elegans) at the L4-stage and using the eggs. Results: Our studies indicated that only spheroids from the U87 cell line have impaired growth after treatment with both compounds, suggesting an increased resistance from T98G spheroids, contrary to what was observed in the monolayer culture, which highlights the need to employ 3D models for future GBM studies. In vitro tests in U87 and T98G cells conclude that the amount of 10B inside the cells is enough for BNCT irradiation. BNCT becomes more effective on T98G after their incubation with Na[8,8′-I2-o-COSAN], whereas no apparent cell-killing effect was observed for untreated cells. Conclusions: These small molecules, particularly [8,8′-I2-o-COSAN]−, are serious candidates for BNCT now that the facilities of accelerator-based neutron sources are more accessible, providing an alternative treatment for resistant glioblastoma

Bridging between Boron & Nanoworld : Versatile Combinations & Emerging Applications

El treball presentat en aquesta tesi implica la recerca duta a terme en el grup de Laboratori de Materials Inorgànics i Catàlisi (LMI) sota la supervisió del Prof. Francesc Teixidor. La tesi es presenta com un compendi d'articles publicats o que es publicaran en un futur proper. La tesi doctoral aprofundeix en el món multifacètic de la química del bor, centrant-se particularment en els θ-metal·lacarborans, i la seva integració amb nanopartícules a mida, descobrint un regne de noves aplicacions i oportunitats. La tesi comença amb una breu Introducció sobre les diverses facetes dels metal·lacarborans i nanopartícules que serveix de base per comprendre els capítols següents. Les investigacions exhaustives comencen amb un estudi detallat sobre les propietats electroquímiques dels metal·lacarborans, particularment cobaltabis(dicarbollur) i ferrabis(dicarbollur), tant en sistemes aquosos com no aquosos amb un estudi comparatiu de Metal·lacarborans vs. Ferrocè. El ferrocè i els seus derivats han estat durant molt de temps la referència interna de referència en electroquímica per a diversos processos. No obstant això, les seves aplicacions estan limitades per problemes relacionats amb la solubilitat i les modificacions químiques. En aquest sentit, el capítol tracta del possible adveniment dels metal·lacarborans com a sistemes de referència interns "universals". El següent capítol sobre Metal·lacarborans & Proteïnes es deriva del coneixement previ de la forta interacció no covalent entre els grups [o-COSAN]- i amina a través de la formació d'enllaços de dihidrogen N-H···B-H. La visualització de proteïnes en la seva forma i entorn nadius sense interferències sempre ha estat una tasca desafiant. Per tant, en aquest estudi ens hem apropat a la 'superfície' d'una proteïna respecte a la seva interacció amb la sonda redox activa de 'molècula petita', [o-COSAN]-, emprant mesuraments electroquímics fàcils i eficaces. Aquests estudis ajuden a obtenir una visió més profunda de les superfícies de les proteïnes que poden ser valuoses per modificar les proteïnes per al disseny de fàrmacs i la biotecnologia. L'adaptació de metal·lacarborans a nanopartícules magnètiques d'enginyeria superficial obre una nova via per explorar i explotar les capacitats d'aquests dos materials. Així, el següent capítol explora la síntesi i caracterització de nanopartícules magnètiques i aprofundeix en les aplicacions de la conjectura: Metal·lacarborans & MNPs. La síntesi de nanopartícules magnètiques col·loïdalment estables i de mida controlada amb propietats magnètiques apreciables sempre ha estat un desafiament. Per tant, en el capítol proposem un mètode nou per a la síntesi de nanopartícules magnètiques col·loïdalment estables sense cap surfactant o agent que cobreixi. L' adaptació dels metal·lacarborans a les nanopartícules magnètiques funcionalitzades a la superfície s' assoleix, una vegada més, explotant els forts enllaços dihidrogen no covalents. El capítol explora l' aplicació d' aquests materials híbrids a la fotocatàlisi d' alcohols, així com la qüestió de modificar un sistema d' acord amb les necessitats. La manca de fluorescència, així com la capacitat dels metal·lacarborans com a catalitzadors eficients i robustos s'exploren més a fons en el capítol sobre Metal·lacarborans & Energia, en el qual s'investiga la capacitat de l' [o-COSAN]- com un elèctrode de "molècula petita". La destresa catalítica dels metal·lacarborans s' estudia en detall. Estenent l'estudi encara més en la falta de fluorescència en metal·lacarborans, s'estudia la capacitat de l' [o-COSAN]- com un extintor de fluorescència eficient respecte als punts quàntics de carboni funcionalitzats amb amines. Els fonaments del procés fotofísic subjacent entre Metal·lacarborans & C-dots s' investiguen a fons i en profunditat. Aquests materials híbrids que incorporen la capacitat de commutació de fluorescència 'on/off' obren noves vies on aventurar-se. La tesi navega a través de diverses aplicacions de metal·lacarborans i nanopartícules amb l'objectiu d'abordar desafiaments crítics i obrir noves vies per a l'avenç científic i el progrés tecnològic.El trabajo presentado en esta tesis implica la investigación llevada a cabo en el grupo de Laboratorio de Materiales Inorgánicos y Catálisis (LMI) bajo la supervisión del Prof. Francesc Teixidor. La tesis se presenta como un compendio de artículos publicados o que se publicarán en un futuro próximo. La tesis doctoral profundiza en el mundo multifacético de la química del boro, centrándose particularmente en los θ-metalacarboranos, y su integración con nanopartículas a medida, descubriendo un reino de nuevas aplicaciones y oportunidades. La tesis comienza con una breve Introducción sobre las diversas facetas de los metalacarboranos y nanopartículas que sirve de base para comprender los capítulos siguientes. Las investigaciones exhaustivas comienzan con un estudio detallado sobre las propiedades electroquímicas de los metalacarboranos, particularmente cobaltabis (dicarbolluro) y ferrabis (dicarbolluro), tanto en sistemas acuosos como no acuosos con un estudio comparativo de Metalacarboranos vs. Ferroceno. El ferroceno y sus derivados han sido durante mucho tiempo la referencia interna de referencia en electroquímica para diversos procesos. En este sentido, el capítulo trata del posible advenimiento de los metalacarboranos como sistemas de referencia internos "universales". El siguiente capítulo sobre Metalacarboranos & Proteínas deriva del conocimiento previo de la fuerte interacción no covalente entre los grupos [o-COSAN]- y amina a través de la formación de enlaces de dihidrógeno N-H···B-H. La visualización de proteínas en su forma y entorno nativos sin interferencias siempre ha sido una tarea desafiante. Por lo tanto, en este estudio hemos abordado la 'superficie' de una proteína con respecto a su interacción con la sonda redox activa basada en una 'molécula pequeña', [o-COSAN]-, empleando mediciones electroquímicas fáciles y eficientes. Estos estudios ayudan a obtener una visión más profunda de las superficies de las proteínas que pueden ser valiosas para modificar las proteínas para el diseño de fármacos y la biotecnología. La adaptación de metalacarboranos a nanopartículas magnéticas de ingeniería superficial abre una nueva vía para explorar y explotar las virtudes de estos dos materiales. Así, el siguiente capítulo explora la síntesis y caracterización de nanopartículas magnéticas y profundiza en las aplicaciones de la conjetura: Metalacarboranos & MNPs. La síntesis de nanopartículas magnéticas coloidalmente estables y de tamaño controlado con propiedades magnéticas atractivas siempre ha sido un desafío. Por ello, en este capítulo proponemos un método novedoso para la síntesis de nanopartículas magnéticas coloidalmente estables sin tensioactivos ni agentes de recubrimiento.La adaptación de los metalacarboranos a las nanopartículas magnéticas funcionalizadas en la superficie se logra, una vez más, explotando los fuertes enlaces de dihidrógeno no covalentes. El capítulo explora la aplicación de estos materiales híbridos en la fotocatálisis de alcoholes, así como la cuestión de modificar un sistema de acuerdo con las necesidades. La falta de fluorescencia, así como la capacidad de los metalacarboranos como catalizadores eficientes y robustos se exploran más a fondo en el capítulo sobre Metalacarboranos & Energía, en el que se investiga la capacidad de [o-COSAN]- como un electrodo tipo "molécula pequeña". La capacidad catalítica de los metalacarboranos se estudia en detalle. Ampliando el estudio sobre la falta de fluorescencia en los metalacarboranos, se estudia la capacidad del [o-COSAN]- como eficiente quencher de fluorescencia con respecto a los puntos cuánticos de carbono funcionalizados con aminas. Los fundamentos del proceso fotofísico subyacente entre Metalacarboranos & C-dots se investigan a fondo y en profundidad. Estos materiales híbridos que incorporan la característica de un modo de conmutación de fluorescencia 'on/off' abren nuevas vías para explorar. La tesis navega a través de diversas aplicaciones de metalacarboranos y nanopartículas con el objetivo de abordar desafíos críticos y abrir nuevas vías para el avance científico y el progreso tecnológico.The work presented in this thesis entails the research carried out in the Inorganic Materials and Catalysis Laboratory group (LMI) under the supervision of Prof. Francesc Teixidor over the course of the Doctoral program. The dissertation is presented as a compendium of articles published or to be published in the near future. The doctoral thesis delves into the multifaceted world of boron chemistry, particularly focusing on θ-metallacarboranes, and their integration with tailored nanoparticles, uncovering a realm of novel applications and opportunities. The characterizations and applications of θ-metallacarboranes and nanoparticles together present a dynamic frontier in modern materials chemistry with an expansive range of possibilities. The thesis begins with a brief Introduction on the diverse facets of metallacarboranes and nanoparticles serving as a foundation for comprehending the subsequent chapters. The comprehensive investigations commence with a detailed and thorough study on the electrochemical properties of metallacarboranes, particularly cobaltabis(dicarbollide) and ferrabis(dicarbollide), in both aqueous and non-aqueous systems with a comparative study of Metallacarboranes vs. Ferrocene. Ferrocene and its derivatives have long been the benchmark internal reference in electrochemistry for various processes. Yet, their applications are constrained by challenges related to solubility and chemical modifications. In this regard, the chapter deals with potential advent of metallacarboranes as 'universal' internal reference systems. The following chapter on Metallacarboranes & Proteins stems from the pre-requisite knowledge of the strong non-covalent interaction between [o-COSAN]- and amine groups through N-H···B-H dihydrogen bond formation. Visualization of proteins in their native form and environment without any interferences has always been a challenging task. Hence, in this study we have tackled the 'surface' of a protein with respect to their interaction with the 'small molecule' redox-active probe, [o-COSAN]-, employing facile and robust electrochemical measurements. These studies aid in gaining a deeper insight on protein surfaces which can be valuable for modifying proteins for drug designs and bio-technology. Tailoring metallacarboranes onto surface engineered magnetic nanoparticles opens a new avenue for exploring and exploiting the virtues of both these materials. Thus, the subsequent chapter explores the synthesis and characterization of magnetic nanoparticles and delves into the applications of the conjecture: Metallacarboranes & MNPs. Synthesis of size-controlled, colloidally stable magnetic nanoparticles with appreciable magnetic properties has always been a challenge. Hence, in the chapter we propose a novel method for the synthesis of colloidally stable magnetic nanoparticles without any surfactant or capping agents. The tailoring of the metallacarboranes onto the surface functionalized magnetic nanoparticles is achieved, yet again, by exploiting the strong non-covalent di-hydrogen bonds. The chapter explores the application of these hybrid materials in photocatalysis of alcohols as well as begets the question of modifying a system according to the needs. The lack of fluorescence as well as the capability of metallacarboranes as efficient and robust catalysts are further explored in the chapter on Metallacarboranes & Energy wherein the ability of [o-COSAN]- as a 'small molecule' electrode is investigated. The catalytic prowess of the metallacarboranes is studied in detail. Extending the study further into the lack of fluorescence in metallacarboranes, the ability of [o-COSAN]- as an efficient fluorescence quencher with regard to amine functionalized carbon quantum dots is studied. The fundamentals of the photophysical process underlying between Metallacarboranes & C-dots are investigated thoroughly and in-depth. These hybrid materials incorporating the virtue of an 'on/off' fluorescence switching mode opens new avenues to be ventured. The thesis navigates through various applications of metallacarboranes and nanoparticles aiming to address critical challenges and open new avenues for scientific advancement and technological progress

Bridging between Boron & Nanoworld: Versatile Combinations & Emerging Applications

El treball presentat en aquesta tesi implica la recerca duta a terme en el grup de Laboratori de Materials Inorgànics i Catàlisi (LMI) sota la supervisió del Prof. Francesc Teixidor. La tesi es presenta com un compendi d'articles publicats o que es publicaran en un futur proper. La tesi doctoral aprofundeix en el món multifacètic de la química del bor, centrant-se particularment en els θ-metal·lacarborans, i la seva integració amb nanopartícules a mida, descobrint un regne de noves aplicacions i oportunitats. La tesi comença amb una breu Introducció sobre les diverses facetes dels metal·lacarborans i nanopartícules que serveix de base per comprendre els capítols següents. Les investigacions exhaustives comencen amb un estudi detallat sobre les propietats electroquímiques dels metal·lacarborans, particularment cobaltabis(dicarbollur) i ferrabis(dicarbollur), tant en sistemes aquosos com no aquosos amb un estudi comparatiu de Metal·lacarborans vs. Ferrocè. El ferrocè i els seus derivats han estat durant molt de temps la referència interna de referència en electroquímica per a diversos processos. No obstant això, les seves aplicacions estan limitades per problemes relacionats amb la solubilitat i les modificacions químiques. En aquest sentit, el capítol tracta del possible adveniment dels metal·lacarborans com a sistemes de referència interns "universals". El següent capítol sobre Metal·lacarborans & Proteïnes es deriva del coneixement previ de la forta interacció no covalent entre els grups [o-COSAN]- i amina a través de la formació d'enllaços de dihidrogen N-H···B-H. La visualització de proteïnes en la seva forma i entorn nadius sense interferències sempre ha estat una tasca desafiant. Per tant, en aquest estudi ens hem apropat a la 'superfície' d'una proteïna respecte a la seva interacció amb la sonda redox activa de 'molècula petita', [o-COSAN]-, emprant mesuraments electroquímics fàcils i eficaces. Aquests estudis ajuden a obtenir una visió més profunda de les superfícies de les proteïnes que poden ser valuoses per modificar les proteïnes per al disseny de fàrmacs i la biotecnologia. L'adaptació de metal·lacarborans a nanopartícules magnètiques d'enginyeria superficial obre una nova via per explorar i explotar les capacitats d'aquests dos materials. Així, el següent capítol explora la síntesi i caracterització de nanopartícules magnètiques i aprofundeix en les aplicacions de la conjectura: Metal·lacarborans & MNPs. La síntesi de nanopartícules magnètiques col·loïdalment estables i de mida controlada amb propietats magnètiques apreciables sempre ha estat un desafiament. Per tant, en el capítol proposem un mètode nou per a la síntesi de nanopartícules magnètiques col·loïdalment estables sense cap surfactant o agent que cobreixi. L' adaptació dels metal·lacarborans a les nanopartícules magnètiques funcionalitzades a la superfície s' assoleix, una vegada més, explotant els forts enllaços dihidrogen no covalents. El capítol explora l' aplicació d' aquests materials híbrids a la fotocatàlisi d' alcohols, així com la qüestió de modificar un sistema d' acord amb les necessitats. La manca de fluorescència, així com la capacitat dels metal·lacarborans com a catalitzadors eficients i robustos s'exploren més a fons en el capítol sobre Metal·lacarborans & Energia, en el qual s'investiga la capacitat de l' [o-COSAN]- com un elèctrode de "molècula petita". La destresa catalítica dels metal·lacarborans s' estudia en detall. Estenent l'estudi encara més en la falta de fluorescència en metal·lacarborans, s'estudia la capacitat de l' [o-COSAN]- com un extintor de fluorescència eficient respecte als punts quàntics de carboni funcionalitzats amb amines. Els fonaments del procés fotofísic subjacent entre Metal·lacarborans & C-dots s' investiguen a fons i en profunditat. Aquests materials híbrids que incorporen la capacitat de commutació de fluorescència 'on/off' obren noves vies on aventurar-se. La tesi navega a través de diverses aplicacions de metal·lacarborans i nanopartícules amb l'objectiu d'abordar desafiaments crítics i obrir noves vies per a l'avenç científic i el progrés tecnològic.El trabajo presentado en esta tesis implica la investigación llevada a cabo en el grupo de Laboratorio de Materiales Inorgánicos y Catálisis (LMI) bajo la supervisión del Prof. Francesc Teixidor. La tesis se presenta como un compendio de artículos publicados o que se publicarán en un futuro próximo. La tesis doctoral profundiza en el mundo multifacético de la química del boro, centrándose particularmente en los θ-metalacarboranos, y su integración con nanopartículas a medida, descubriendo un reino de nuevas aplicaciones y oportunidades. La tesis comienza con una breve Introducción sobre las diversas facetas de los metalacarboranos y nanopartículas que sirve de base para comprender los capítulos siguientes. Las investigaciones exhaustivas comienzan con un estudio detallado sobre las propiedades electroquímicas de los metalacarboranos, particularmente cobaltabis (dicarbolluro) y ferrabis (dicarbolluro), tanto en sistemas acuosos como no acuosos con un estudio comparativo de Metalacarboranos vs. Ferroceno. El ferroceno y sus derivados han sido durante mucho tiempo la referencia interna de referencia en electroquímica para diversos procesos. En este sentido, el capítulo trata del posible advenimiento de los metalacarboranos como sistemas de referencia internos "universales". El siguiente capítulo sobre Metalacarboranos & Proteínas deriva del conocimiento previo de la fuerte interacción no covalente entre los grupos [o-COSAN]- y amina a través de la formación de enlaces de dihidrógeno N-H···B-H. La visualización de proteínas en su forma y entorno nativos sin interferencias siempre ha sido una tarea desafiante. Por lo tanto, en este estudio hemos abordado la 'superficie' de una proteína con respecto a su interacción con la sonda redox activa basada en una 'molécula pequeña', [o-COSAN]-, empleando mediciones electroquímicas fáciles y eficientes. Estos estudios ayudan a obtener una visión más profunda de las superficies de las proteínas que pueden ser valiosas para modificar las proteínas para el diseño de fármacos y la biotecnología. La adaptación de metalacarboranos a nanopartículas magnéticas de ingeniería superficial abre una nueva vía para explorar y explotar las virtudes de estos dos materiales. Así, el siguiente capítulo explora la síntesis y caracterización de nanopartículas magnéticas y profundiza en las aplicaciones de la conjetura: Metalacarboranos & MNPs. La síntesis de nanopartículas magnéticas coloidalmente estables y de tamaño controlado con propiedades magnéticas atractivas siempre ha sido un desafío. Por ello, en este capítulo proponemos un método novedoso para la síntesis de nanopartículas magnéticas coloidalmente estables sin tensioactivos ni agentes de recubrimiento.La adaptación de los metalacarboranos a las nanopartículas magnéticas funcionalizadas en la superficie se logra, una vez más, explotando los fuertes enlaces de dihidrógeno no covalentes. El capítulo explora la aplicación de estos materiales híbridos en la fotocatálisis de alcoholes, así como la cuestión de modificar un sistema de acuerdo con las necesidades. La falta de fluorescencia, así como la capacidad de los metalacarboranos como catalizadores eficientes y robustos se exploran más a fondo en el capítulo sobre Metalacarboranos & Energía, en el que se investiga la capacidad de [o-COSAN]- como un electrodo tipo "molécula pequeña". La capacidad catalítica de los metalacarboranos se estudia en detalle. Ampliando el estudio sobre la falta de fluorescencia en los metalacarboranos, se estudia la capacidad del [o-COSAN]- como eficiente quencher de fluorescencia con respecto a los puntos cuánticos de carbono funcionalizados con aminas. Los fundamentos del proceso fotofísico subyacente entre Metalacarboranos & C-dots se investigan a fondo y en profundidad. Estos materiales híbridos que incorporan la característica de un modo de conmutación de fluorescencia 'on/off' abren nuevas vías para explorar. La tesis navega a través de diversas aplicaciones de metalacarboranos y nanopartículas con el objetivo de abordar desafíos críticos y abrir nuevas vías para el avance científico y el progreso tecnológico.The work presented in this thesis entails the research carried out in the Inorganic Materials and Catalysis Laboratory group (LMI) under the supervision of Prof. Francesc Teixidor over the course of the Doctoral program. The dissertation is presented as a compendium of articles published or to be published in the near future. The doctoral thesis delves into the multifaceted world of boron chemistry, particularly focusing on θ-metallacarboranes, and their integration with tailored nanoparticles, uncovering a realm of novel applications and opportunities. The characterizations and applications of θ-metallacarboranes and nanoparticles together present a dynamic frontier in modern materials chemistry with an expansive range of possibilities. The thesis begins with a brief Introduction on the diverse facets of metallacarboranes and nanoparticles serving as a foundation for comprehending the subsequent chapters. The comprehensive investigations commence with a detailed and thorough study on the electrochemical properties of metallacarboranes, particularly cobaltabis(dicarbollide) and ferrabis(dicarbollide), in both aqueous and non-aqueous systems with a comparative study of Metallacarboranes vs. Ferrocene. Ferrocene and its derivatives have long been the benchmark internal reference in electrochemistry for various processes. Yet, their applications are constrained by challenges related to solubility and chemical modifications. In this regard, the chapter deals with potential advent of metallacarboranes as 'universal' internal reference systems. The following chapter on Metallacarboranes & Proteins stems from the pre-requisite knowledge of the strong non-covalent interaction between [o-COSAN]- and amine groups through N-H···B-H dihydrogen bond formation. Visualization of proteins in their native form and environment without any interferences has always been a challenging task. Hence, in this study we have tackled the 'surface' of a protein with respect to their interaction with the 'small molecule' redox-active probe, [o-COSAN]-, employing facile and robust electrochemical measurements. These studies aid in gaining a deeper insight on protein surfaces which can be valuable for modifying proteins for drug designs and bio-technology. Tailoring metallacarboranes onto surface engineered magnetic nanoparticles opens a new avenue for exploring and exploiting the virtues of both these materials. Thus, the subsequent chapter explores the synthesis and characterization of magnetic nanoparticles and delves into the applications of the conjecture: Metallacarboranes & MNPs. Synthesis of size-controlled, colloidally stable magnetic nanoparticles with appreciable magnetic properties has always been a challenge. Hence, in the chapter we propose a novel method for the synthesis of colloidally stable magnetic nanoparticles without any surfactant or capping agents. The tailoring of the metallacarboranes onto the surface functionalized magnetic nanoparticles is achieved, yet again, by exploiting the strong non-covalent di-hydrogen bonds. The chapter explores the application of these hybrid materials in photocatalysis of alcohols as well as begets the question of modifying a system according to the needs. The lack of fluorescence as well as the capability of metallacarboranes as efficient and robust catalysts are further explored in the chapter on Metallacarboranes & Energy wherein the ability of [o-COSAN]- as a 'small molecule' electrode is investigated. The catalytic prowess of the metallacarboranes is studied in detail. Extending the study further into the lack of fluorescence in metallacarboranes, the ability of [o-COSAN]- as an efficient fluorescence quencher with regard to amine functionalized carbon quantum dots is studied. The fundamentals of the photophysical process underlying between Metallacarboranes & C-dots are investigated thoroughly and in-depth. These hybrid materials incorporating the virtue of an 'on/off' fluorescence switching mode opens new avenues to be ventured. The thesis navigates through various applications of metallacarboranes and nanoparticles aiming to address critical challenges and open new avenues for scientific advancement and technological progress.Universitat Autònoma de Barcelona. Programa de Doctorat en Químic

Potential application of metallacarboranes as an internal reference: an electrochemical comparative study to ferrocene

Ferrocene and its derivatives have been extensively used as an internal reference in electrochemical processes. Yet, they possess limitations such as solvent restrictions that require chemical modifications. In this regard, we have studied the use of metallacarboranes [3,3'-M(1,2-C2B9H11)2]- (M = Co, Fe) as general internal reference systems and have proven their suitability by thoroughly investigating their electrochemical properties in both aqueous and organic electrolytes without any derivatization.This work was funded by the Spanish Ministry of Science, through the ‘‘Severo Ochoa’’ Programme for Centres of Excellence in R&D (CEX2019-000917-S) as well as the Ministerio de Economia y Competitividad (PID2019-106832RB-I00), (PID2020- 116728RB-I00, CTQ2015-71955-RED ELECTROBIONET) and Generalitat de Catalunya (2017SGR1720) are appreciated. J. A. M. Xavier acknowledges DOC-FAM programme under the Marie Sklodowska-Curie grant agreement no. 754397 and is enrolled in the PhD programme in UAB. Support from the Community of Madrid (TRANSNANOAVANSENS S2018/NMT-4349), is acknowledged.With funding from the Spanish government through the ‘Severo Ochoa Centre of Excellence’ accreditation (CEX2019-000917-S).Peer reviewe

Noncovalently Linked Metallacarboranes on Functionalized Magnetic Nanoparticles as Highly Efficient, Robust, and Reusable Photocatalysts in Aqueous Medium

A successful homogeneous photoredox catalyst has been fruitfully heterogenized on magnetic nanoparticles (MNPs) coated with a silica layer, keeping intact its homogeneous catalytic properties but gaining others due to the easy magnetic separation and recyclability. The amine-terminated magnetic silica nanoparticles linked noncovalently to H[3,3′-Co(1,2-C2B9H11)2]− (H[1]), termed MSNPs-NH2@H[1], are highly stable and do not produce any leakage of the photoredox catalyst H[1] in water. The magnetite MNPs were coated with SiO2 to provide colloidal stability and silanol groups to be tethered to amine-containing units. These were the MSNPs-NH2 on which was anchored, in water, the cobaltabis(dicarbollide) complex H[1] to obtain MSNPs-NH2@H[1]. Both MSNPs-NH2 and MSNPs-NH2@H[1] were evaluated to study the morphology, characterization, and colloidal stability of the MNPs produced. The heterogeneous MSNP-NH2@H[1] system was studied for the photooxidation of alcohols, such as 1-phenylethanol, 1-hexanol, 1,6-hexanediol, or cyclohexanol among others, using catalyst loads of 0.1 and 0.01 mol %. Surfactants were introduced to prevent the aggregation of MNPs, and cetyl trimethyl ammonium chloride was chosen as a surfactant. This provided adequate stability, without hampering quick magnetic separation. The results proved that the catalysis could be speeded up if aggregation was prevented. The recyclability of the catalytic system was demonstrated by performing 12 runs of the MSNPs-NH2@H[1] system, each one without loss of selectivity and yield. The cobaltabis(dicarbollide) catalyst supported on silica-coated magnetite nanoparticles has proven to be a robust, efficient, and easily reusable system for the photooxidation of alcohols in water, resulting in a green and sustainable heterogeneous catalytic system.This research has been financed by MINECO (CTQ2016-75150-R and CTQ2015-66143-P) and Generalitat de Catalunya (2017 SGR 1720). The “Severo Ochoa” Program for Centers of Excellence in R&D 234 (SEV-2015-0496) is appreciated. J.A.M.X. thanks the DOC-FAM programme funded by the European Union’s Horizon 2020 research and innovation programme under the Marie Sklodowska-Curie grant agreement No. 754397.Peer reviewe

Single stop analysis of a protein surface using molecular probe electrochemistry

Visualization of a protein in its native form and environment without any interference has always been a challenging task. Contrary to the assumption that protein surfaces are smooth, they are in fact highly irregular with undulating surfaces. Hence, in this study, we have tackled this ambiguous nature of the 'surface' of a protein by considering the 'effective' protein surface (EPS) with respect to its interaction with the geometrically well-defined and structurally inert anionic molecule [3,3'-Co(1,2-C2B9H11)2]-, abbreviated as [o-COSAN]-, whose stability, propensity for amine residues, and self-assembling abilities are well reported. This study demonstrates the intricacies of protein surfaces exploiting simple electrochemical measurements using a 'small molecule' redox-active probe. This technique offers the advantage of not utilizing any harsh experimental conditions that could alter the native structure of the protein and hence the protein integrity is retained. Identification of the amino acid residues which are most involved in the interactions with [3,3'-Co(1,2-C2B9H11)2]- and how a protein's environment affects these interactions can help in gaining insights into how to modify proteins to optimize their interactions particularly in the fields of drug design and biotechnology. In this research, we have demonstrated that [3,3'-Co(1,2-C2B9H11)2]- anionic small molecules are excellent candidates for studying and visualizing protein surfaces in their natural environment and allow proteins to be classified according to the surface composition, which imparts their properties. [3,3'-Co(1,2-C2B9H11)2]- 'viewed' each protein surface differently and hence has the potential to act as a simple and easy to handle cantilever for measuring and picturing protein surfaces.This work received funding from the Spanish Ministry of Science, through the “Severo Ochoa” Programme for Centres of Excellence in R&D (CEX2019-000917-S) as well as the Spanish Ministerio de Ciencia e Innovación (PID2019-106832RB-I00) and Generalitat de Catalunya (2017SGR1720). J. A. M. Xavier acknowledges the DOC-FAM programme under the Marie Sklodowska-Curie grant agreement No. 754397 and is enrolled in the PhD programme in UAB.With funding from the Spanish government through the ‘Severo Ochoa Centre of Excellence’ accreditation (CEX2019-000917-S).Peer reviewe

Light-Induced On/Off Switching of the Surfactant Character of the o-Cobaltabis(dicarbollide) Anion with No Covalent Bond Alteration

Cobaltabis(dicarbollide) anion ([o-COSAN]- ) is a well-known metallacarborane with multiple applications in a variety of fields. In aqueous solution, the cisoid rotamer is the most stable disposition in the ground state. The present work provides theoretical evidence on the possibility to photoinduce the rotation from the cisoid to the transoid rotamer, a conversion that can be reverted when the ground state is repopulated. The non-radiative decay mechanisms proposed in this work are coherent with the lack of fluorescence observed in 3D fluorescence mapping experiments performed on [o-COSAN]- and its derivatives. This phenomenon induced by light has the potential to destruct the vesicles and micelles cisoid [o-COSAN]- typically forms in aqueous solution, which could lead to promising applications, particularly in the field of nanomedicine.This work was supported by the Generalitat Valenciana (GV, project GV/2020/226), Generalitat de Catalunya (2017 SGR 1720), and the Spanish Ministerio de Ciencia e Innovación (MICINN, projects CTQ2017-87054-C2-2–304-P and PID2019-106832RB-I00). A.M.A.A. is grateful to the Erasmus+ Programme of the European Comission for his Erasmus Mundus TCCM scholarship. A.F.-M. is grateful to the GV and the European Social Fund for the postdoctoral contract APOSTD/2019/149 and to the MICINN for the Juan de la Cierva contract IJC2019-039297-I. D.R.-S. is grateful to the MICINN for the “Ramón y Cajal” grant (RYC-2015–19234). “Severo Ochoa” Program for Centers of Excellence in R&D 234 (SEV-2015-0496) is appreciated. J. A. M. Xavier acknowledges DOC-FAM programme under the Marie Sklodowska-Curie grant agreement No. 754397 and is enrolled in the PhD program of the UAB. Computations have been conducted at the local QCEXVAL and the LluisVives and Tirant III clusters of the Servei d'Informàtica (University of Valencia). We thank Dr. Jordi Faraudo (ICMAB-CSIC) for the scientific discussions.With funding from the Spanish government through the ‘Severo Ochoa Centre of Excellence’ accreditation (CEX2019-000917-S).Peer reviewe

How to switch from a poor PEDOT:X oxygen evolution reaction (OER) to a good one. A study on dual redox reversible PEDOT:metallacarborane

Over the years, extensive research has been carried out to optimize the oxygen evolution reaction (OER) by adopting different techniques as well as catalysts. Conducting organic polymers such as PEDOT have been employed to study the reaction but have failed to lower the over-potential for the reaction. Here we show electrochemically made, intimately blended, dual redox reversible materials incorporating PEDOT and metallacarboranes. The metallacarboranes act as doping agents but with tunable E1/2 potentials. The tunability of E1/2 allows the overlapping of the two redox potentials which subsequently leads to their synergy. The physico-chemical properties of the metallacarboranes fade and become integrated with PEDOT to form a dual redox reversible system. Therefore, the properties of the dopant are modified by the polymer. Thus, due to its high E1/2, the Co4+/3+ couple would not be an efficient electrocatalyst for water oxidation but when it is immersed in the PEDOT matrix the Co4+/3+ potential is more accessible so that very low overpotential values are obtained, which justifies the title of the work, How to switch from a poor PEDOT:X oxygen evolution reaction (OER) to a good one. The dual redox reversible system has been extensively characterized and has been shown to be a promising candidate for the water oxidation reaction

Water soluble organometallic small molecules as promising antibacterial agents : synthesis, physical–chemical properties and biological evaluation to tackle bacterial infections

The Na[3,3′-Fe(8-I-1,2-C2B9H10)2] and Na[2,2′-M(1,7-C2B9H11)] (M = Co3+, Fe3+) small molecules are synthesized and the X-ray structures of [(H3O)(H2O)5][2,2′-Co(1,7-C2B9H11)2] and [Cs(MeCN)][8,8′-I2-Fe(1,2 C2B9H10)2], both displaying a transoid conformation of the [M(C2B9)2]− framework, are reported. Importantly, the supramolecular structure of [(H3O)(H2O)5][2,2′-Co(1,7-C2B9H11)2] presents 2D layers leading to a lamellar arrangement of the anions while the cation layers form polymeric water rings made of six- and four-membered rings of water molecules connected via OH⋯H hydrogen bonds; B–H⋯O contacts connect the cationic and anionic layers. Herein, we highlight the influence of the ligand isomers (ortho-/meta-), the metal effect (Co3+/Fe3+) on the same isomer, as well as the influence of the presence of the iodine atoms on the physical–chemical and biological properties of these molecules as antimicrobial agents to tackle antibiotic-resistant bacteria, which were tested with four Gram-positive bacteria, five Gram-negative bacteria, and three Candida albicans strains that have been responsible for human infections. We have demonstrated an antimicrobial effect against Candida species (MIC of 2 and 3 nM for Na[3,3′-Co(8-I-1,2-C2B9H10)2] and Na[2,2′-Co(1,7-C2B9H11)2], respectively), and against Gram-positive and Gram-negative bacteria, including multiresistant MRSA strains (MIC of 6 nM for Na[3,3′-Co(8-I-1,2-C2B9H10)2]). The selectivity index for antimicrobial activity of Na[3,3′-Co(1,2-C2B9H11)2] and Na[3,3′-Co(8-I-1,2-C2B9H10)2] compounds is very high (165 and 1180, respectively), which reveals that these small anionic metallacarborane molecules may be useful to tackle antibiotic-resistant bacteria. Moreover, we have demonstrated that the outer membrane of Gram-negative bacteria constitutes an impermeable barrier for the majority of these compounds. Nonetheless, the addition of two iodine groups in the structure of the parent Na[3,3′-Co(1,2-C2B9H11)2] had an improved effect (3–7 times) against Gram-negative bacteria. Possibly the changes in their physical–chemical properties make the meta-isomers and the ortho-di-iodinated small molecules more permeable for crossing this barrier. It should be emphasized that the most active metallabis(dicarbollide) small molecules are both transoid conformers in contrast to the ortho- [3,3′-Co(1,2-C2B9H11)2]− that is cisoid. The fact that these small molecules cross the mammalian membrane and have antimicrobial properties but low toxicity for mammalian cells (high selectivity index, SI) represents a promising tool to treat infectious intracellular bacteria. Since there is an urgent need for antibiotic discovery and development, this study represents a relevant advance in the field.peerReviewe

Effect of Metformin and Lifestyle Interventions on Mortality in the Diabetes Prevention Program and Diabetes Prevention Program Outcomes Study

ObjectiveTo determine whether metformin or lifestyle modification can lower rates of all-cause and cause-specific mortality in the Diabetes Prevention Program and Diabetes Prevention Program Outcomes Study.Research design and methodsFrom 1996 to 1999, 3,234 adults at high risk for type 2 diabetes were randomized to an intensive lifestyle intervention, masked metformin, or placebo. Placebo and lifestyle interventions stopped in 2001, and a modified lifestyle program was offered to everyone, but unmasked study metformin continued in those originally randomized. Causes of deaths through 31 December 2018 were adjudicated by blinded reviews. All-cause and cause-specific mortality hazard ratios (HRs) were estimated from Cox proportional hazards regression models and Fine-Gray models, respectively.ResultsOver a median of 21 years (interquartile range 20-21), 453 participants died. Cancer was the leading cause of death (n = 170), followed by cardiovascular disease (n = 131). Compared with placebo, metformin did not influence mortality from all causes (HR 0.99 [95% CI 0.79, 1.25]), cancer (HR 1.04 [95% CI 0.72, 1.52]), or cardiovascular disease (HR 1.08 [95% CI 0.70, 1.66]). Similarly, lifestyle modification did not impact all-cause (HR 1.02 [95% CI 0.81, 1.28]), cancer (HR 1.07 [95% CI 0.74, 1.55]), or cardiovascular disease (HR 1.18 [95% CI 0.77, 1.81]) mortality. Analyses adjusted for diabetes status and duration, BMI, cumulative glycemic exposure, and cardiovascular risks yielded results similar to those for all-cause mortality.ConclusionsCancer was the leading cause of mortality among adults at high risk for type 2 diabetes. Although metformin and lifestyle modification prevented diabetes, neither strategy reduced all-cause, cancer, or cardiovascular mortality rates