Regioselective Ring-Opening of Oxetanes Catalyzed by Lewis Superacid Al(C6F5)3

This study details an aluminum-catalyzed regioselective isomerization of 2,2-disubstituted oxetanes to yield homoallylic alcohols. The reaction takes place in toluene at 40 °C, employing 1 mol % of Al(C6F5)3 as catalyst. This catalytic system shows a wide substrate scope (12 examples). The optimized conditions are especially useful for electron-rich aryl oxetanes, completely suppressing the formation of allyl isomers and reducing the amount of the dimer by-product. The synthetic applicability of the reported methodology is demonstrated by the enantioselective formal synthesis of curcuquinone and the σ1 receptor agonist RC-33

Tripodal BODIPY-tagged and functional molecular probes: synthesis, computational investigations and explorations by multiphoton fluorescence lifetime imaging microscopy

A range of novel BODIPY derivatives with a tripodal aromatic core was synthesized and characterized spectroscopically. These new fluorophores showed promising features as probes for in vitro assays in live cells and offer strategic routes for further functionalization towards hybrid nanomaterials. Incorporation of biotin tags facilitated proof-of-concept access to targeted bioconjugates as molecular probes. Computational explorations using DFT and TD-DFT calculations identified the most stable tripodal linker conformations and predicted their absorption and emission behavior. The uptake and speciation of these molecules in living prostate cancer cells was imaged by single- and two-photon excitation techniques coupled with two-photon fluorescence lifetime imaging (2P FLIM)The authors thank the ERC for funding through the Consolidator Grant O2Sense (617107), ERC PoC Tools-To-Sense (963937), and the University of Bath for the URSA-Science Strategic PhD studentship to ML. SIP also thanks the following grants for funding: STFC CDN+ Biosensing and NIR Imaging of New Biomarkers for Prostate Cancer, BBSRC (BB/W019655/1: Multi User High- Content Confocal Fluorescence Microscope); EP/K0171 60/1: ‘New manufacturable approaches to the deposition and patterning of graphene materials’; EP/L016354/1: EPSRC Centre for Doctoral Training in Sustainable Chemical Technologies EP/ G03768X/1: Doctoral Training Centre in Sustainable Chemical Technologies. DGC thanks to the Ministerio de Ciencia, Innovaci' on y Universidades (Spain) for funding (TED2021132779B-100 and TED2021-129876B I00

Homochiral Metal-Organic Frameworks for Enantioselective Separations in Liquid Chromatography

Selective separation of enantiomers is a substantial challenge for the pharmaceutical industry. Chromatography on chiral stationary phases is the standard method, but at a very high cost for industrial-scale purification owing to the high cost of the chiral stationary phases. Typically, these materials are poorly robust, expensive to manufacture and often too specific for a single desired substrate, lacking desirable versatility across different chiral analytes. Here we disclose a porous, robust homochiral metal-organic framework (MOF), TAMOF-1, built from copper(II) and an affordable linker prepared from natural L-histidine. TAMOF-1 has shown to be able to separate a variety of model racemic mixtures, including drugs, in a wide range of solvents of different polarity, outperforming several commercial chiral columns for HPLC separations. Although not exploited in the present article, it is worthy to mention that the preparation of this new material is scalable to the multikilogram scale, opening unprecedented possibilities for low-energy chiral separation at the industrial scale

Causal Effect of MMP-1 (Matrix Metalloproteinase-1), MMP-8, and MMP-12 Levels on Ischemic Stroke: A Mendelian Randomization Study.

MMP (matrix metalloproteinase) levels have been widely associated with ischemic stroke risk and poststroke outcome. However, their role as a risk factor or as a subeffect because of ischemia is uncertain. We performed a literature search of genome-wide studies that evaluate serum/plasma levels of MMPs. We used a 2-sample Mendelian randomization approach to evaluate the causality of MMP levels on ischemic stroke risk or poststroke outcome, using 2 cohorts: MEGASTROKE (n=440 328) and GODs (n=1791). Genome-wide association studies of MMP-1, MMP-8, and MMP-12 plasma/serum levels were evaluated. A significant association, which was also robust in the sensitivity analysis, was found with all ischemic strokes: MMP-12 (odds ratio=0.90 [95% CI, 0.86–0.94]; q value=7.43×10−5), and with subtypes of stroke, large-artery atherosclerosis: MMP-1 (odds ratio=0.95 [95% CI, 0.92–0.98]; q value=0.01) and MMP-12 (odds ratio=0.71 [95% CI, 0.65–0.77]; q value=5.11×10−14); small-vessel occlusion: MMP-8 (odds ratio=1.24 [95% CI, 1.06–1.45]; q value=0.03). No associations were found in relation to stroke outcome. Our study suggests a causal link between lower serum levels of MMP-12 and the risk of ischemic stroke, lower serum levels of MMP-1 and MMP-12 and the risk of large-artery stroke and higher serum levels of MMP-8 and the risk of lacunar stroke

RP11-362K2.2 : RP11-767I20.1 Genetic Variation Is Associated with Post-Reperfusion Therapy Parenchymal Hematoma. A GWAS Meta-Analysis

Stroke is one of the most common causes of death and disability. Reperfusion therapies are the only treatment available during the acute phase of stroke. Due to recent clinical trials, these therapies may increase their frequency of use by extending the time-window administration, which may lead to an increase in complications such as hemorrhagic transformation, with parenchymal hematoma (PH) being the more severe subtype, associated with higher mortality and disability rates. Our aim was to find genetic risk factors associated with PH, as that could provide molecular targets/pathways for their prevention/treatment and study its genetic correlations to find traits sharing genetic background. We performed a GWAS and meta-analysis, following standard quality controls and association analysis (fastGWAS), adjusting age, NIHSS, and principal components. FUMA was used to annotate, prioritize, visualize, and interpret the meta-analysis results. The total number of patients in the meta-analysis was 2034 (216 cases and 1818 controls). We found rs79770152 having a genome-wide significant association (beta 0.09, p-value 3.90 x 10(-8)) located in the RP11-362K2.2:RP11-767I20.1 gene and a suggestive variant (rs13297983: beta 0.07, p-value 6.10 x 10(-8)) located in PCSK5 associated with PH occurrence. The genetic correlation showed a shared genetic background of PH with Alzheimer's disease and white matter hyperintensities. In addition, genes containing the ten most significant associations have been related to aggregated amyloid-beta, tau protein, white matter microstructure, inflammation, and matrix metalloproteinases.Peer reviewe

CCDC 1898970: Experimental Crystal Structure Determination

Related Article: M. Nieves Corella-Ochoa, Jesús B. Tapia, Heather N. Rubin, Vanesa Lillo, Jesús González-Cobos, José Luis Núñez-Rico, Salvador R.G. Balestra, Neyvis Almora-Barrios, Marina Lledós, Arnau Güell-Bara, Juanjo Cabezas-Giménez, Eduardo C. Escudero-Adán, Anton Vidal-Ferran, Sofía Calero, Melissa Reynolds, Carlos Martí-Gastaldo, José Ramón Galán-Mascarós|2019|J.Am.Chem.Soc.|141|14306|doi:10.1021/jacs.9b0650

CCDC 1898811: Experimental Crystal Structure Determination

Related Article: M. Nieves Corella-Ochoa, Jesús B. Tapia, Heather N. Rubin, Vanesa Lillo, Jesús González-Cobos, José Luis Núñez-Rico, Salvador R.G. Balestra, Neyvis Almora-Barrios, Marina Lledós, Arnau Güell-Bara, Juanjo Cabezas-Giménez, Eduardo C. Escudero-Adán, Anton Vidal-Ferran, Sofía Calero, Melissa Reynolds, Carlos Martí-Gastaldo, José Ramón Galán-Mascarós|2019|J.Am.Chem.Soc.|141|14306|doi:10.1021/jacs.9b0650

CCDC 1898969: Experimental Crystal Structure Determination

Related Article: M. Nieves Corella-Ochoa, Jesús B. Tapia, Heather N. Rubin, Vanesa Lillo, Jesús González-Cobos, José Luis Núñez-Rico, Salvador R.G. Balestra, Neyvis Almora-Barrios, Marina Lledós, Arnau Güell-Bara, Juanjo Cabezas-Giménez, Eduardo C. Escudero-Adán, Anton Vidal-Ferran, Sofía Calero, Melissa Reynolds, Carlos Martí-Gastaldo, José Ramón Galán-Mascarós|2019|J.Am.Chem.Soc.|141|14306|doi:10.1021/jacs.9b0650

CCDC 1898971: Experimental Crystal Structure Determination

Related Article: M. Nieves Corella-Ochoa, Jesús B. Tapia, Heather N. Rubin, Vanesa Lillo, Jesús González-Cobos, José Luis Núñez-Rico, Salvador R.G. Balestra, Neyvis Almora-Barrios, Marina Lledós, Arnau Güell-Bara, Juanjo Cabezas-Giménez, Eduardo C. Escudero-Adán, Anton Vidal-Ferran, Sofía Calero, Melissa Reynolds, Carlos Martí-Gastaldo, José Ramón Galán-Mascarós|2019|J.Am.Chem.Soc.|141|14306|doi:10.1021/jacs.9b0650

RP11-362K2.2:RP11-767I20.1 Genetic Variation Is Associated with Post-Reperfusion Therapy Parenchymal Hematoma. A GWAS Meta-Analysis

Stroke is one of the most common causes of death and disability. Reperfusion therapies are the only treatment available during the acute phase of stroke. Due to recent clinical trials, these therapies may increase their frequency of use by extending the time-window administration, which may lead to an increase in complications such as hemorrhagic transformation, with parenchymal hematoma (PH) being the more severe subtype, associated with higher mortality and disability rates. Our aim was to find genetic risk factors associated with PH, as that could provide molecular targets/pathways for their prevention/treatment and study its genetic correlations to find traits sharing genetic background. We performed a GWAS and meta-analysis, following standard quality controls and association analysis (fastGWAS), adjusting age, NIHSS, and principal components. FUMA was used to annotate, prioritize, visualize, and interpret the meta-analysis results. The total number of patients in the meta-analysis was 2034 (216 cases and 1818 controls). We found rs79770152 having a genome-wide significant association (beta 0.09, p-value 3.90 × 10−8) located in the RP11-362K2.2:RP11-767I20.1 gene and a suggestive variant (rs13297983: beta 0.07, p-value 6.10 × 10−8) located in PCSK5 associated with PH occurrence. The genetic correlation showed a shared genetic background of PH with Alzheimer’s disease and white matter hyperintensities. In addition, genes containing the ten most significant associations have been related to aggregated amyloid-β, tau protein, white matter microstructure, inflammation, and matrix metalloproteinases