Variable Temperature Synthesis of Tunable Flame-Generated Carbon Nanoparticles

In this study, flame-formed carbon nanoparticles of different nanostructures have been produced by changing the flame temperature. Raman spectroscopy has been used for the characterization of the carbon nanoparticles, while the particle size has been obtained by online measurements made by electrical mobility analysis. The results show that, in agreement with recent literature data, a large variety of carbon nanoparticles, with a different degree of graphitization, can be produced by changing the flame temperature. This methodology allows for the synthesis of very small carbon nanoparticles with a size of about 3–4 nm and with different graphitic orders. Under the perspective of the material synthesis process, the variable-temperature flame-synthesis of carbon nanoparticles appears as an attractive procedure for a cost-effective and easily scalable production of highly tunable carbon nanoparticles

Discovery and optimization of benzoylpiperidine derivatives as new reversible, potent and selective MAGL inhibitors

The serine hydrolase monoacylglycerol lipase (MAGL) is the main responsible of the degradation of 2-arachidonoylglycerol, an endocannabinoid implicated in several physiological processes. Moreover, MAGL is involved in the formation of pro-tumorigenic signaling molecules. MAGL inhibition is considered a valid therapeutic approach to treat several pathological conditions, including several types of cancer.[1] So far, only a limited number of MAGL inhibitors have been discovered and most of them are characterized by an irreversible mechanism of action, determining the occurrence of undesired effects. In this study we identified a reversible MAGL inhibitor by a structure-based virtual screening analysis. With the aim of identifying more potent and selective MAGL inhibitors, chemical modifications were introduced to the original compound to improve both potency and selectivity.[2] The structural optimization led to the obtainment of nanomolar inhibitors (Figure 1), which are selective over other hydrolases and cannabinoid receptors. These new inhibitors exert an appreciable antiproliferative activity in cancer cells and are able to inhibit MAGL in in vivo assays. [1] Mulvihill MM, Nomura DK, Life Sci. 2013; 92(8-9):492-497. [2] Granchi C, Rizzolio F, Palazzolo S, Carmignani S, Macchia M, Saccomanni G, Manera C, Martinelli A, Minutolo F, Tuccinardi T, J Med Chem. 2016; 59(22):10299-10314

Identification of Lactate Dehydrogenase 5 Inhibitors using Pharmacophore- Driven Consensus Docking

Background: Human lactate dehydrogenase 5 (hLDH5) represents a promising anticancer target, particularly for the treatment of hypoxic tumors, where it is often hyperexpressed. In fact, by catalyzing the reduction of pyruvate to lactate, hLDH5 allows the survival of tumor cells under hypoxic conditions by means of glycolysis. Despite the efforts dedicated to the identification and development of hLDH5 inhibitors, only few compounds showing promising activity in cancer cell lines have been reported. Objective: In the present study, we developed a virtual screening (VS) protocol aimed at identifying new small molecule inhibitors of hLDH5. Method: The VS strategy consisted in a pharmacophore-driven consensus docking (CD) approach, combining a structure-based pharmacophore screening and CD protocol employing three different docking methods. Results: The VS protocol was applied to filter the Enamine commercial database and allowed the selection of three candidate ligands to be subjected to hLDH5 inhibition assays. One of the selected compounds showed a promising activity, compared to its low molecular weight, with an IC50 of 180.7 ± 16.5 μM. Conclusion: We identified a new small-molecule inhibitor of hLDH5 that can be considered as a new lead for the development of potent hLDH5 inhibitors. Moreover, these results demonstrate the reliability of the VS protocol developed

Insights into incipient soot formation by atomic force microscopy

Abstract Combustion-generated soot particles can have significant impact on climate, environment and human health. Thus, understanding the processes governing the formation of soot particles in combustion is a topic of ongoing research. In this study, high-resolution atomic force microscopy (AFM) was used for direct imaging of the building blocks forming the particles in the early stages of soot formation. Incipient soot particles were collected right after the particle nucleation zone of a slightly sooting ethylene/air laminar premixed flame at atmospheric pressure and analyzed by AFM after a rapid sublimation procedure. Our data shed light on one of the most complex and still debated aspect on soot formation, i.e., the nucleation process. The molecular constituents of the initial particles have been individually analyzed in detail in their chemical/structural characteristics. Our data demonstrate the large complexity/variety of the aromatic compounds which are the building blocks of the initial soot particles. Nevertheless, some fundamental and specific characteristics have been clearly ascertained. These include a significant presence of penta-rings as opposed to the purely benzenoid aromatic compounds and the noticeable presence of aliphatic side-chains. In addition, there were indications for the presence of persistent π radicals. Incipient soot was also investigated by Raman spectroscopy, the results of which agreed in terms of chemical and structural composition of the particles with those obtained by AFM

Buone pratiche per la tutela della qualità dell’aria indoor. L’esperienza del Treno Verde 2017

La qualità dell’aria ed in particolare la qualità dell’aria all’interno degli edifici, nell’ambito dei temi relativi a salute e benessere della popolazione, assume oggi, importanza sempre più rilevante. I principali problemi legati alla qualità dell'aria Indoor - IAQ (Indoor Air Quality) - sono strettamente correlati alla concentrazione e definizione dei principali composti inquinanti presenti negli ambienti confinati. L’irrinunciabile tema del risparmio energetico ha prodotto precauzioni che hanno condotto, oltre a un maggior isolamento degli edifici ed a una diminuzione dei tassi di ventilazione, anche all’utilizzo di nuovi materiali e di nuove apparecchiature, cioè a misure che aumentano le concentrazioni di agenti inquinanti che si formano nei locali. Nel corso degli ultimi decenni si è difatti assistito a un progressivo deterioramento della qualità dell’aria negli ambienti confinati. Numerosi studi scientifici hanno dimostrato la presenza, nell’aria degli ambienti di vita, di agenti inquinanti a bassa concentrazione di difficile misurazione che possono determinare effetti sulla salute non ancora completamente noti. Gli inquinanti indoor, che possono agire singolarmente o combinati con altri fattori, determinano una diminuzione del comfort ambientale e un rischio per la salute; sono agenti di tipo chimico (composti organici e inorganici), fisico (radiazioni ionizzanti e non ionizzanti) e biologico (microrganismi, muffe, acari). Considerato che gran parte della popolazione trascorre il proprio tempo in ambienti confinati, l’esposizione all’inquinamento indoor è dominante rispetto a quella outdoor. Vengono considerati come sintomi specifici, non gravi, che possono impattare sulla salute e quindi, sui costi sociali del paese: malattie respiratorie trasmissibili, allergie e asma, sintomi della sindrome dell’edificio malato (SBS, dall’inglese Sick Building Syndrome)

Soot inception: A DFT study of σ and π dimerization of resonantly stabilized aromatic radicals

Recent advances in the soot studies have shown experimental evidences of π-radicals and cross-linked structures among the molecular constituents of just-nucleated soot particles. π-radicals could have an important role in particle nucleation by increasing the binding energy between polycyclic aromatic hydrocarbons with respect to pure van der Waals interactions. In this work we use density functional theory by Grimme D3 dispersion correction (DFT-D3) with hybrid functional and localized Gaussian basis set (B3LYP/6-31G**) to analyze and classify the clustering behaviors of two aromatic radicals visualized experimentally by atomic force microscopy (Commodo et al. Combust. Flame 205: 154–164, 2019). These aromatic radicals have different topological structures and delocalization of the unpaired electron. The binding energy and energy bandgap characteristics of the clusters are calculated. The theoretical results show a different clustering behavior for the two aromatic radicals. The one with a partial localization of the unpaired electron tends to form a σ-dimer; conversely, the radical with a greater delocalization of the unpaired electron leads to π-stacking formation with a slight overbinding of few kcal mol−1 with respect to pure van der Waals interactions and a marked lowering of the energy bandgap. The formation of π-stacking induced by delocalized π-radicals could in part explain some spectroscopic evidences observed during soot nucleation. © 2020 Elsevier Lt

Testing the performance of sensors for ozone pollution monitoring in a citizen science approach

Tropospheric ozone (O3) is an environmental pollutant of growing concern, especially in suburban and rural areas where the density of air quality monitoring stations is not high. In this type of areas citizen science strategies can be useful tools for awareness raising, but sensor technologies must be validated before sensor data are communicated to the public. In this work, the performance under field conditions of two custom-made types of ozone sensing devices, based on metal-oxide and electrochemical sensors, was tested. A large array of 132 metal-oxide (Sensortech MICS 2614) and 11 electrochemical (Alphasense) ozone sensors, built into 44 sensing devices, was co-located at reference stations in Italy (4 stations) and Spain (5). Mean R2 between sensor and reference data was 0.88 (0.78–0.96) and 0.89 (0.73–0.96) for Captor (metal-oxide) and Raptor (electrochemical) nodes. The metal-oxide sensors showed an upper limit (approximately 170 µg/m3) implying that these sensors may be useful to communicate mean ozone concentrations but not peak episodes. The uncertainty of the nodes was 10% between 100 and 150 µg/m3 and 20% between 150 and 200 µg/m3, for Captors, and 10% for >100 µg/m3 for Raptors. Operating both types of nodes up to 5 months did not evidence any clear influence of drifts. The use of these sensors in citizen science can be a useful tool for awareness raising. However, significant data processing efforts are required to ensure high data quality, and thus machine learning strategies are advisable. Relative uncertainties should always be reported when communicating ozone concentration data from sensing nodes.Peer ReviewedPostprint (published version

First-in-Class Dual Targeting Compounds for the Management of Seizures in Glucose Transporter Type 1 Deficiency Syndrome

The genetic disorder glucose transporter type 1 deficiency syndrome (GLUT1-DS) heavily affects the main intake of energy in tissues and determines the most relevant outcomes at the central nervous system (CNS) district, which is highly dependent on glucose. Herein, we report the design and development of a set of compounds bearing the glucosyl and galactosyl moieties. We assessed their ability to enhance the GLUT1 mediated glucose intake in non-small-cell lung cancer (NSCLC) cells and to inhibit the carbonic anhydrase (CA; EC 4.2.1.1) isoforms implicated in the physiopathology of uncontrolled seizures associated to epilepsy (i.e., I, II, IV, VA, VB, and XII). The binding mode of 8 in adduct with hCA II was determined by X-ray crystallography. Among the selected derivatives, compound 4b proved effective in suppressing the occurrence of uncontrolled seizures on the in vivo induced maximal electroshock (MES) model and thus gives sustainment of an unprecedently reported pharmacological approach for the management of GLUT1-DS associated diseases

Functionalized aliphatic polyketones with germicide activity

The COVID-19 pandemic has further confirmed to the community that direct contact with contaminated surfaces and objects represents an important source of pathogen spreading among humans. Therefore, it is of paramount importance to design effective germicidal paints to ensure a rapid and potent disinfectant action of surfaces. In this work, we design novel germicide polymeric coatings by inserting quaternary ammonium and sugar groups on the macromolecular backbone, thus respectively endowing the polymer with germicide features and hydrophilicity to interact with the surfaces. An aliphatic polyketone was selected as a starting polymer matrix that was functionalized with primary amine derivatives via the Paal–Knorr reaction. The resulting polymers were deposited on cellulose filter papers and checkboard charts with excellent coating yield and substrate coverage as determined by scanning electron microscopy for cellulose. Remarkably, the substrates coated by the functional polymers bearing quaternary ammonium compounds showed excellent bactericide properties with antibacterial rate of 99% and logarithmic reduction of >3. Notably, the polymers with higher hydrophobicity showed better retention on the substrate after being treated with water at neutral pH

Design, synthesis, ADME and biological evaluation of benzylpiperidine and benzylpiperazine derivatives as novel reversible monoacylglycerol lipase (MAGL) inhibitors.

The degradation of the endocannabinoid 2-arachidonoylglycerol is mediated by the enzyme monoacylglycerol lipase (MAGL), thus generating arachidonic acid, the precursor of prostaglandins and other pro-inflammatory mediators. MAGL also contributes to the hydrolysis of monoacylglycerols into glycerol and fatty acids in peripheral body districts, which may act as pro-tumorigenic signals. For this reason, MAGL inhibitors have been considered as interesting therapeutic agents for their anti-nociceptive, anti-inflammatory, antioxidant and anti-cancer properties. So far, only a limited series of reversible MAGL inhibitors, which are devoid of side effects shown by irreversible inhibitors in animal models, have been reported. Here we optimized a class of benzylpiperidine and benzylpiperazine-based compounds for a reversible MAGL inhibition. The best MAGL inhibitors of this class, compounds 28 and 29, showed a very good inhibition potency, both on the isolated enzyme and in U937 cells, as confirmed by molecular modeling studies that predicted their binding mode into the MAGL active site. Both compounds are characterized by a high selectivity for MAGL versus other serine hydrolases including enzymes of the endocannabinoid system, as confirmed by ABPP experiments in mouse brain membranes. Moreover, very good properties concerning ADME parameters and low in vivo toxicity have been observed for both compounds