Carborane-stilbene dyads: influence of substituents and cluster isomers on the photoluminescence properties

Two novel styrene-containing meta-carborane derivatives substituted at the second carbon cluster atom (Cc) with either a methyl (Me), or a phenyl (Ph) group, are introduced herein alongside with a new set of stilbene-containing ortho- (o-) and meta- (m-) carborane dyads. The latter set of compounds has been prepared from styrenecontaining carborane derivatives via Heck coupling reaction. High regioselectivity has been achieved for these compounds by using a combination of palladium complexes [Pd2(dba)3]/[Pd(t-Bu3P)2] as a catalytic system, yielding exclusively E isomers. All compounds have been fully characterized and the crystal structures of seven of them analyzed by X-ray diffraction. The absorption spectra of these compounds are similar to those of their respective fluorophore groups (styrene or stilbene), showing very low influence of the substituent (Me or Ph) linked to the second Cc atom or the cluster isomer (o- or m-). On the other hand, fluorescence spectroscopy revealed high emission intensities for Me-o-carborane derivatives, whereas their Ph-o-carborane analogues evidenced an almost total lack of fluorescence, confirming the significant role of the substituent bound to the adjacent Cc in o-carboranes. In contrast, all the m-carborane derivatives display similar photoluminescence (PL) behavior regardless of the substituent attached to the second Cc, demonstrating its small influence on the emission properties. Additionally, m-carborane derivatives are significantly more fluorescent than their o- counterparts, reaching quantum yield values as high as 30.2%. Regarding the solid state emission, only stilbene-containing Ph-o-carborane derivatives, which showed very low fluorescence in solution, exhibited a notable PL emission in films attributed to the aggregation-induced emission. DFT calculations were performed to successfully complement the photoluminescence studies, supporting the experimentally observed photophysical behavior of the styrene and stilbene-containing carborane derivatives. In conclusion, in this work is proved that it is possible to tailor the PL properties of the carborane-stilbene dyads by changing the Cc substituent and the carborane isomer.This work has been supported by Ministerio de Economía y Competitividad, MINECO, (CTQ2013-44670-R and CTQ2013-41339-P), and Generalitat de Catalunya (2014/SGR/149). Theoretical calculations have been achieved using computers from the Centro Técnico de Informática del Consejo Superior de Investigaciones Ciéntificas (CTI-CSIC). ICMAB acknowledges financial support from the MINECO, through the “Severo Ochoa” Program for Centers of Excellence in R&D (SEV- 2015-0496).Peer reviewe

Treatment with tocilizumab or corticosteroids for COVID-19 patients with hyperinflammatory state: a multicentre cohort study (SAM-COVID-19)

Objectives: The objective of this study was to estimate the association between tocilizumab or corticosteroids and the risk of intubation or death in patients with coronavirus disease 19 (COVID-19) with a hyperinflammatory state according to clinical and laboratory parameters. Methods: A cohort study was performed in 60 Spanish hospitals including 778 patients with COVID-19 and clinical and laboratory data indicative of a hyperinflammatory state. Treatment was mainly with tocilizumab, an intermediate-high dose of corticosteroids (IHDC), a pulse dose of corticosteroids (PDC), combination therapy, or no treatment. Primary outcome was intubation or death; follow-up was 21 days. Propensity score-adjusted estimations using Cox regression (logistic regression if needed) were calculated. Propensity scores were used as confounders, matching variables and for the inverse probability of treatment weights (IPTWs). Results: In all, 88, 117, 78 and 151 patients treated with tocilizumab, IHDC, PDC, and combination therapy, respectively, were compared with 344 untreated patients. The primary endpoint occurred in 10 (11.4%), 27 (23.1%), 12 (15.4%), 40 (25.6%) and 69 (21.1%), respectively. The IPTW-based hazard ratios (odds ratio for combination therapy) for the primary endpoint were 0.32 (95%CI 0.22-0.47; p < 0.001) for tocilizumab, 0.82 (0.71-1.30; p 0.82) for IHDC, 0.61 (0.43-0.86; p 0.006) for PDC, and 1.17 (0.86-1.58; p 0.30) for combination therapy. Other applications of the propensity score provided similar results, but were not significant for PDC. Tocilizumab was also associated with lower hazard of death alone in IPTW analysis (0.07; 0.02-0.17; p < 0.001). Conclusions: Tocilizumab might be useful in COVID-19 patients with a hyperinflammatory state and should be prioritized for randomized trials in this situatio

Dietary α‐Linolenic Acid, Marine ω‐3 Fatty Acids, and Mortality in a Population With High Fish Consumption: Findings From the PREvención con DIeta MEDiterránea (PREDIMED) Study

Background: Epidemiological evidence suggests a cardioprotective role of α‐linolenic acid (ALA), a plant‐derived ω‐3 fatty acid. It is unclear whether ALA is beneficial in a background of high marine ω‐3 fatty acids (long‐chain n‐3 polyunsaturated fatty acids) intake. In persons at high cardiovascular risk from Spain, a country in which fish consumption is customarily high, we investigated whether meeting the International Society for the Study of Fatty Acids and Lipids recommendation for dietary ALA (0.7% of total energy) at baseline was related to all‐cause and cardiovascular disease mortality. We also examined the effect of meeting the society's recommendation for long‐chain n‐3 polyunsaturated fatty acids (≥500 mg/day). Methods and Results: We longitudinally evaluated 7202 participants in the PREvención con DIeta MEDiterránea (PREDIMED) trial. Multivariable‐adjusted Cox regression models were fitted to estimate hazard ratios. ALA intake correlated to walnut consumption (r=0.94). During a 5.9‐y follow‐up, 431 deaths occurred (104 cardiovascular disease, 55 coronary heart disease, 32 sudden cardiac death, 25 stroke). The hazard ratios for meeting ALA recommendation (n=1615, 22.4%) were 0.72 (95% CI 0.56–0.92) for all‐cause mortality and 0.95 (95% CI 0.58–1.57) for fatal cardiovascular disease. The hazard ratios for meeting the recommendation for long‐chain n‐3 polyunsaturated fatty acids (n=5452, 75.7%) were 0.84 (95% CI 0.67–1.05) for all‐cause mortality, 0.61 (95% CI 0.39–0.96) for fatal cardiovascular disease, 0.54 (95% CI 0.29–0.99) for fatal coronary heart disease, and 0.49 (95% CI 0.22–1.01) for sudden cardiac death. The highest reduction in all‐cause mortality occurred in participants meeting both recommendations (hazard ratio 0.63 [95% CI 0.45–0.87]). Conclusions: In participants without prior cardiovascular disease and high fish consumption, dietary ALA, supplied mainly by walnuts and olive oil, relates inversely to all‐cause mortality, whereas protection from cardiac mortality is limited to fish‐derived long‐chain n‐3 polyunsaturated fatty acids. Clinical Trial Registration URL: http://www.Controlled-trials.com/. Unique identifier: ISRCTN35739639

International nosocomial infection control consortium (INICC) report, data summary of 36 countries, for 2004-2009

The results of a surveillance study conducted by the International Nosocomial Infection Control Consortium (INICC) from January 2004 through December 2009 in 422 intensive care units (ICUs) of 36 countries in Latin America, Asia, Africa, and Europe are reported. During the 6-year study period, using Centers for Disease Control and Prevention (CDC) National Healthcare Safety Network (NHSN; formerly the National Nosocomial Infection Surveillance system [NNIS]) definitions for device-associated health care-associated infections, we gathered prospective data from 313,008 patients hospitalized in the consortium's ICUs for an aggregate of 2,194,897 ICU bed-days. Despite the fact that the use of devices in the developing countries' ICUs was remarkably similar to that reported in US ICUs in the CDC's NHSN, rates of device-associated nosocomial infection were significantly higher in the ICUs of the INICC hospitals; the pooled rate of central line-associated bloodstream infection in the INICC ICUs of 6.8 per 1,000 central line-days was more than 3-fold higher than the 2.0 per 1,000 central line-days reported in comparable US ICUs. The overall rate of ventilator-associated pneumonia also was far higher (15.8 vs 3.3 per 1,000 ventilator-days), as was the rate of catheter-associated urinary tract infection (6.3 vs. 3.3 per 1,000 catheter-days). Notably, the frequencies of resistance of Pseudomonas aeruginosa isolates to imipenem (47.2% vs 23.0%), Klebsiella pneumoniae isolates to ceftazidime (76.3% vs 27.1%), Escherichia coli isolates to ceftazidime (66.7% vs 8.1%), Staphylococcus aureus isolates to methicillin (84.4% vs 56.8%), were also higher in the consortium's ICUs, and the crude unadjusted excess mortalities of device-related infections ranged from 7.3% (for catheter-associated urinary tract infection) to 15.2% (for ventilator-associated pneumonia). Copyright © 2012 by the Association for Professionals in Infection Control and Epidemiology, Inc. Published by Elsevier Inc. All rights reserved

Disseny, preparació i estudi de compostos rics en bor amb propietats fotoluminiscents

Following in the same line of research initiated by the Catalysis and Inorganic Synthesis Group within the ICMAB time ago, this work is mainly focused on the synthesis of carborane derivatives with styrenyl groups via nucleophilic substitution reactions, followed by the incorporation of these derivatives to different types of platforms and structures in order to study their photoluminescence properties. Starting from these compounds, in which the o-carborane cluster is of closo nature (therefore neutral from electronic point of view), their corresponding nido (anionic) derivatives have been obtained, by the cluster’s partial deboronation reaction in basic medium. These derivatives have been fully characterised using common spectroscopic techniques such as infrared spectroscopy, NMR spectroscopy, mass spectrometry, elemental analysis and in some cases, X-ray diffraction. Subsequently, photoluminescence studies have been performed, indicating that although the derivatives of methyl-o-carborane and monosubstituted o-carborane exhibit an intense fluorescence, their phenyl-o-carborane analogues show almost no light emission at all. In order to explain such phenomenon, the cyclic voltammetry has been studied as well as DFT theoretical calculations performed, leading to the conclusion that the lack of fluorescence for the phenyl-o-carborane derivative is most probably due to a photoinduced electronic transfer process (PET). Different types of carbosilane and poly(aryl-ether) dendrimers have been chosen as platforms to which the styrenyl group-containing compounds have been incorporated into. To achieve this objective, these carboranyl derivatives have been adequately functionalised to contain a terminal Si-H bond and, in this manner, to carry out the hydrosilylation reaction of them with different type and generations of dendrimers that contain a variable number of terminal alkenes. In this way, structures bearing from 3 to 12 carborane clusters at the periphery have been obtained. Polyanionic dendrimers have also been generated via partial deboronation reactions of closo clusters to the respective nido derivatives, and isolated as alkaline salts. All of these synthesised dendrimers have been fully characterised. For the poly(aryl-ether) dendrimers, their thermal properties have been studied by thermogravimetric analysis (TGA), as well as their photophysical properties. The influence of the different substituents of the clusters (phenyl or methyl), number of clusters and the electronic nature of the cage on the photoluminescence has been studied. Those compounds that contain methyl-o-carborane have shown the highest emission quantic yields. These dendrimers, due to their elevated boron content, are considered to be good candidates for future biomedical applications, among others Boron Neutron Capture Therapy (BNCT) and other applications such as antivirals or bactericides. The family formed by cubic silsesquioxanes or POSS constitutes another interesting platform to be taken into account, when considering the incorporation of our carborane derivatives bearing the styrenyl group. With the aim of retaining the structure of these compounds, they have been reacted with octavinylsilsesquioxane via olefin metathesis reactions, yielding macromolecules that contain 8 carborane clusters at the periphery. As was previously accomplished for the poly(aryl-ether) dendrimers, their corresponding polyanionic derivatives have been also obtained, using the same partial deboronation reaction of the closo cluster to the respective nido species. All resulting compounds have been fully characterised by different spectroscopic techniques and elemental analysis. The thermal properties of neutral POSS with closocarboranes have been studied by TGA, showing a remarkable thermal stability. This fact lead us to carry out a more complete study of POSS, previously treated at 600 ºC for 1 hour, using powder X-rays diffraction (XRD) technique and transmission electron microscopy (TEM). Photoluminescence studies of neutral POSS have revealed a different behaviour concerning emissions data, respect to their styrenyl-carborane precursors. In this case, the phenyl-o-carborane derivative presents the highest intensity of emission, whereas the monosubstituted o-carborane species shows a total fluorescence quenching. DFT calculations have been done, both in fundamental and excited states, corroborating the experimental results. By analysing the photoluminescent properties of the isolated starting materials and after anchoring them to different platforms (dendrimers and POSS), it has been observed that the carborane cluster and its substituents play an important and interesting role within these properties. Therefore, we decided to go even further and synthesize, using diverse synthetic strategies (addition, hydrosilylation, nucleophilic substitution or Heck reactions, etc), compounds bearing carborane clusters and different fluorophore groups, such as fluorene, anthracene or stilbene. All of these compounds have been adequately characterised and there photoluminescent properties studied. In all cases, it has been observed that when the fluorophore group is not directly bonded to the cluster and is situated away from it, the emission intensities are quite elevated, whereas if there is an aromatic group directly bonded to the cluster (phenyl or fluorene) and the fluorophore group is close to it in space, a quenching of the fluorescence is produced, which, depending on the type of fluorophore, is more or less efficient. This phenomenon is in close agreement with the results obtained for the phenyl-o-carborane derivatives, for the starting carboranestyrenyl- carborane derivatives as well as for the poly(aryl-ether) dendrimers. During the three months stage at the University of York, different compounds derived from the o-carborane and incorporating at least 1 mesogen derivative of cholesterol have been synthesised, with the aim of obtaining new materials with liquid crystal properties. Once these compounds have been characterised, they have also been analysed by differential scanning calorimetry (DSC) and polarised optical microscopy (POM), to confirm that in general all compounds synthesised by hydrosilylation reaction do not show mesogenic properties, with the exception of the compound bearing 4 mesogens within its structure. On the other hand, all of the compounds synthesised via olefinic metathesis, show interesting mesogenic properties, exhibiting, in all cases, a chiral nematic mesophase (N*). Moreover, in the case of the methyl-o-carborane derivative, a Blue Phase (BP*) and a chiral smectic mesophase A (SmA*) are exhibited during the cooling cycle. These results indicate that for the latter compounds, the incorporation of the carborane clusters does not destroy the mesomorphic behaviour of the mesogen, but in addition, confers it new and interesting mesogenic properties

Disseny, preparació i estudi de compostos rics en bor amb propietats fotoluminiscents

Following in the same line of research initiated by the Catalysis and Inorganic Synthesis Group within the ICMAB time ago, this work is mainly focused on the synthesis of carborane derivatives with styrenyl groups via nucleophilic substitution reactions, followed by the incorporation of these derivatives to different types of platforms and structures in order to study their photoluminescence properties. Starting from these compounds, in which the o-carborane cluster is of closo nature (therefore neutral from electronic point of view), their corresponding nido (anionic) derivatives have been obtained, by the cluster's partial deboronation reaction in basic medium. These derivatives have been fully characterised using common spectroscopic techniques such as infrared spectroscopy, NMR spectroscopy, mass spectrometry, elemental analysis and in some cases, X-ray diffraction. Subsequently, photoluminescence studies have been performed, indicating that although the derivatives of methyl-o-carborane and monosubstituted o-carborane exhibit an intense fluorescence, their phenyl-o-carborane analogues show almost no light emission at all. In order to explain such phenomenon, the cyclic voltammetry has been studied as well as DFT theoretical calculations performed, leading to the conclusion that the lack of fluorescence for the phenyl-o-carborane derivative is most probably due to a photoinduced electronic transfer process (PET). Different types of carbosilane and poly(aryl-ether) dendrimers have been chosen as platforms to which the styrenyl group-containing compounds have been incorporated into. To achieve this objective, these carboranyl derivatives have been adequately functionalised to contain a terminal Si-H bond and, in this manner, to carry out the hydrosilylation reaction of them with different type and generations of dendrimers that contain a variable number of terminal alkenes. In this way, structures bearing from 3 to 12 carborane clusters at the periphery have been obtained. Polyanionic dendrimers have also been generated via partial deboronation reactions of closo clusters to the respective nido derivatives, and isolated as alkaline salts. All of these synthesised dendrimers have been fully characterised. For the poly(aryl-ether) dendrimers, their thermal properties have been studied by thermogravimetric analysis (TGA), as well as their photophysical properties. The influence of the different substituents of the clusters (phenyl or methyl), number of clusters and the electronic nature of the cage on the photoluminescence has been studied. Those compounds that contain methyl-o-carborane have shown the highest emission quantic yields. These dendrimers, due to their elevated boron content, are considered to be good candidates for future biomedical applications, among others Boron Neutron Capture Therapy (BNCT) and other applications such as antivirals or bactericides. The family formed by cubic silsesquioxanes or POSS constitutes another interesting platform to be taken into account, when considering the incorporation of our carborane derivatives bearing the styrenyl group. With the aim of retaining the structure of these compounds, they have been reacted with octavinylsilsesquioxane via olefin metathesis reactions, yielding macromolecules that contain 8 carborane clusters at the periphery. As was previously accomplished for the poly(aryl-ether) dendrimers, their corresponding polyanionic derivatives have been also obtained, using the same partial deboronation reaction of the closo cluster to the respective nido species. All resulting compounds have been fully characterised by different spectroscopic techniques and elemental analysis. The thermal properties of neutral POSS with closocarboranes have been studied by TGA, showing a remarkable thermal stability. This fact lead us to carry out a more complete study of POSS, previously treated at 600 ºC for 1 hour, using powder X-rays diffraction (XRD) technique and transmission electron microscopy (TEM). Photoluminescence studies of neutral POSS have revealed a different behaviour concerning emissions data, respect to their styrenyl-carborane precursors. In this case, the phenyl-o-carborane derivative presents the highest intensity of emission, whereas the monosubstituted o-carborane species shows a total fluorescence quenching. DFT calculations have been done, both in fundamental and excited states, corroborating the experimental results. By analysing the photoluminescent properties of the isolated starting materials and after anchoring them to different platforms (dendrimers and POSS), it has been observed that the carborane cluster and its substituents play an important and interesting role within these properties. Therefore, we decided to go even further and synthesize, using diverse synthetic strategies (addition, hydrosilylation, nucleophilic substitution or Heck reactions, etc), compounds bearing carborane clusters and different fluorophore groups, such as fluorene, anthracene or stilbene. All of these compounds have been adequately characterised and there photoluminescent properties studied. In all cases, it has been observed that when the fluorophore group is not directly bonded to the cluster and is situated away from it, the emission intensities are quite elevated, whereas if there is an aromatic group directly bonded to the cluster (phenyl or fluorene) and the fluorophore group is close to it in space, a quenching of the fluorescence is produced, which, depending on the type of fluorophore, is more or less efficient. This phenomenon is in close agreement with the results obtained for the phenyl-o-carborane derivatives, for the starting carboranestyrenyl- carborane derivatives as well as for the poly(aryl-ether) dendrimers. During the three months stage at the University of York, different compounds derived from the o-carborane and incorporating at least 1 mesogen derivative of cholesterol have been synthesised, with the aim of obtaining new materials with liquid crystal properties. Once these compounds have been characterised, they have also been analysed by differential scanning calorimetry (DSC) and polarised optical microscopy (POM), to confirm that in general all compounds synthesised by hydrosilylation reaction do not show mesogenic properties, with the exception of the compound bearing 4 mesogens within its structure. On the other hand, all of the compounds synthesised via olefinic metathesis, show interesting mesogenic properties, exhibiting, in all cases, a chiral nematic mesophase (N*). Moreover, in the case of the methyl-o-carborane derivative, a Blue Phase (BP*) and a chiral smectic mesophase A (SmA*) are exhibited during the cooling cycle. These results indicate that for the latter compounds, the incorporation of the carborane clusters does not destroy the mesomorphic behaviour of the mesogen, but in addition, confers it new and interesting mesogenic properties

Electrochemistry and Photoluminescence of Icosahedral Carboranes, Boranes, Metallacarboranes, and Their Derivatives

Icosahedral boranes, carboranes, and metallacarboranes are extraordinarily robust compounds with desirable properties such as thermal and redox stability, chemical inertness, low nucleophilicity, and high hydrophobicity, making them attractive for several applications such as medicine, nanomaterials, molecular electronics, energy, catalysis, environmental chemistry, and other areas. The hydrogen atoms in these clusters can be replaced by convenient groups that open the way to a chemical alternative to conventional "organic" or "organometallic" realms. Icosahedral boron cluster derivatives have been reviewed from different perspectives; however, there is a need for a review dedicated to the redox and photophysical characteristics of easily accessible borane and carborane derivatives, which are excellent materials for a wide range of applications. This review deals with the redox properties and photoluminescence behavior of this collection of compounds, as well as their influence on the properties of materials and devices whose working principles are related to electron-transfer or electron-promotion phenomena. We hope that this review will be of great value to boron cluster scientists and researchers working in the photoluminescence and electrochemistry fields who are interested in exploring the possibilities of these unique and promising systems