Suchergebnisse

Abstract
Crystalline silica (CS) is a well-known human carcinogen and freshly fractured CS is strongly held to be more toxic than aged dust. Mechanical fracturing indeed generates on CS surface a specific family of Nearly-Free Silanols (NFS), a moiety that was proved to destabilize cell membranes and initiate inflammation in vivo. During milling, silica nanoparticles are also generated, however their contribution to the overall toxicity of quartz is still largely unexplored. Nanoquartz can be synthetized via bottom-up methods, but the surface chemistry of those crystals strongly differs from nanoparticles resulting from fracturing. We report here a top-down milling procedure to obtain a nanometric quartz that shares with fractured quartz the key surface properties relevant to toxicity. Fracturing procedure was optimized by coupling dry and wet milling steps, using water as a dispersing agent, and varying milling times and rotational speeds. We obtained a set of samples that would be classified as nanomaterials under EU CLP regulation (>50% of particles in number are < 100 nm) and exhibited a strong tendency to form submicrometric agglomerates. Deagglomeration with surfactants or simulated body fluids was negligible. Partial lattice amorphization and bimodal crystallite domain size were observed, as confirmed by the presence of two distinct domains of scattering with nanometric (< 50 nm) and submicrometric (0.8-1 µm) crystallite size. A moderate membranolytic activity, which nicely correlated with the amount of surface NFS, signalled that our nanoquartz may induce inflammation in vivo. Overall, a membranolytic nanoquartz for investigating the toxic activity of nanometric silica was obtained.

Abstract
Respirable crystalline silica (RCS) is the leading cause of occupational respiratory diseases worldwide. RCS is associated with inflammatory lung reactions, which can lead to silicosis, cancer, and autoimmune diseases. The extreme variability of silica specimens, including its amorphous forms, the surface heterogeneity, and variable toxicity effects, generated one of the most intriguing enigmas in particle toxicology, i.e., deciphering which physico-chemical features explain and predict the variable hazard of silica. Using a set of ad hoc prepared synthetic and natural quartz particles, we have identified a unique subfamily of surface silanols as a key initiator of the toxicity of silica particles. These moieties, namely the "nearly-free silanols" (NFS), appear on the surface of quartz when crystals are fractured, and their amount can be modulated by physico-chemical processes. The peculiar spatial arrangement of NFS was demonstrated as the most energetically favorable and selective for interacting zwitterionic phospholipids that make up cell membranes. The toxic activity of NFS was also confirmed with amorphous nanosilica synthesized at high temperatures, and our recent findings suggest that NFS could impart toxic properties to other silica polymorphs and hydroxylated surfaces, including aluminosilicates and engineered stones. Overall, NFS occurrence accounts for the origin and variability of the toxicity of silica, opening perspectives for controlling RCS hazard, and may contribute to understand other important interfacial phenomena of hydroxylated materials.

A small library of 2,6- and 3,5-distyrenyl-substituted carborane-BODIPY dyes was efficiently synthesized by means of a Pd-catalyzed Heck coupling reaction. Styrenyl-carborane derivatives were exploited as molecular tools to insert two carborane clusters into the fluorophore core and to extend the π-conjugation of the final molecule in a single synthetic step. The synthetic approach allows to increase the molecular diversity of this class of fluorescent dyes by the synthesis of symmetric or asymmetric units with enhanced boron content. The structural characterization and the photoluminescence (PL) properties of synthesized dyes were evaluated, and the structure/properties relationships have been investigated by theoretical calculations. The developed compounds exhibit a significant bathochromic shift compared to their parent fluorophore scaffolds, and absorption and emission patterns were practically unaffected by the different substituents (Me or Ph) on the Ccluster atom (Cc) of the carborane cage or the cluster isomer (ortho- or meta-carborane). Remarkably, the presence of carborane units at 2,6-positions of the fluorophore produced a significant increase of the emission fluorescent quantum yields, which could be slightly tuned by changing the Cc-substituent and the carborane isomer, as well as introducing ethylene glycol groups at the meso-position of the BODIPY. ; We would like to acknowledge Dr. Emanuele Priola (UniTO) and Dr. Francesco Marra (UniTO) for technical support, and Prof. Claudio Medana (UniTO) for HRMS measurements. We acknowledge the italian MIUR, Huvepharma Italia srl, Regione Piemonte and Cassa di Risparmio di Torino for financial support. This research was funded by MINECO ((CTQ2016-75150-R) Agencia Estatal de Investigación AEI from MICINN (PID2019-106832RB-100/AEI/10.13039/501100011033) and Generalitat de Catalunya (2017 SGR1720). The work was also supported by the MICINN through the Severo Ochoa Program for Centers of Excellence FUNFUTURE (CEX2019-000917-S). Sohini Sinha was enrolled in the PhD Program of UAB. S. S. acknowledges financial support from DOC-FAM, European Union's Horizon 2020 research and innovation programme under the Marie Sklodowska-Curie grant agreement No 754397. ; With funding from the Spanish government through the 'Severo Ochoa Centre of Excellence' accreditation (CEX2019-000917-S). ; Peer reviewed