Publications

Abstract Quorum sensing (QS) has a central role in biofilm lifestyle and antimicrobial resistance, and disrupting these signaling pathways is a promising strategy to control bacterial pathogenicity and virulence. In this study, the efficacy of three structurally related benzaldehydes (4-hydroxybenzaldehyde, 4-hydroxy-3-methoxybenzaldehyde (vanillin) and 4-hydroxy-3,5-dimethoxybenzaldehyde (syringaldehyde)) in disrupting the las and pqs systems of Pseudomonas aeruginosa was investigated using bioreporter strains and computational simulations. Additionally, these benzaldehydes were combined with tobramycin and ciprofloxacin antibiotics to evaluate their ability to increase antibiotic efficacy in preventing and eradicating P. aeruginosa biofilms. To this end, the total biomass, metabolic activity and culturability of the biofilm cells were determined. In vitro assays results indicated that the aromatic aldehydes have potential to inhibit the las and pqs systems by > 80 %. Molecular docking studies supported these findings, revealing the aldehydes binding in the same pocket as the natural ligands or receptor proteins (LasR, PQSA, PQSE, PQSR). Benzaldehydes were shown to act as virulence factor attenuators, with vanillin achieving a 48 % reduction in pyocyanin production. The benzaldehyde-tobramycin combination led not only to a 60 % reduction in biomass production but also to a 90 % reduction in the metabolic activity of established biofilms. A similar result was observed when benzaldehydes were combined with ciprofloxacin. 4-Hydroxybenzaldehyde demonstrated relevant action in increasing biofilm susceptibility to ciprofloxacin, resulting in a 65 % reduction in biomass. This study discloses, for the first time, that the benzaldehydes studied are potent QS inhibitors and also enhancers of antibiotics antibiofilm activity against P. aeruginosa.

Abstract Lewy body dementia (LBD) represents the second most common neurodegenerative dementia but is a quite underexplored therapeutic area. Nepflamapimod (1) is a brain-penetrant selective inhibitor of the alpha isoform of the mitogen-activated serine/threonine protein kinase (MAPK) p38 alpha, recently repurposed for LBD due to its remarkable antineuroinflammatory properties. Neuroprotective propargylamines are another class of molecules with a therapeutical potential against LBD. Herein, we sought to combine the antineuroinflammatory core of 1 and the neuroprotective propargylamine moiety into a single molecule. Particularly, we inserted a propargylamine moiety in position 4 of the 2,6-dichlorophenyl ring of 1, generating neflamapimod-propargylamine hybrids 3 and 4. These hybrids were evaluated using several cell models, aiming to recapitulate the complexity of LBD pathology through different molecular mechanisms. The N-methyl-N-propargyl derivative 4 showed a nanomolar p38 alpha-MAPK inhibitory activity (IC50 = 98.7 nM), which is only 2.6-fold lower compared to that of the parent compound 1, while displaying no hepato- and neurotoxicity up to 25 mu M concentration. It also retained a similar immunomodulatory profile against the N9 microglial cell line. Gratifyingly, at 5 mu M concentration, 4 demonstrated a neuroprotective effect against dexamethasone-induced reactive oxygen species production in neuronal cells that was higher than that of 1.

Abstract Antimicrobial resistance (AMR) poses a global threat to human health, as exemplified by the devastating impact of ESKAPE pathogens, reducing treatment options, increasing disease burden, and elevating death rates due to treatment failure. This looming health threat has rekindled interest in the development of new antimicrobial therapies. In this study, a library of 49 structurally related quaternary heteronium salts (QHSs), such as quaternary ammonium and phosphonium compounds, was screened at a concentration of 32 mu g/mL against five ESKAPE pathogens (methicillin-resistant Staphylococcus aureus (MRSA), Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Escherichia coli), as well as the yeast -like fungus Candida albicans. The preliminary high -throughput screening (HTS) data revealed that QHSs with longer alkyl chain lengths (>= 12 carbons) exhibited broad-spectrum antimicrobial activity, with the C14-C16 homologous demonstrating the highest potency. The alkyl-triphenylphosphonium salts 1a-g exhibited the most significant antimicrobial activity among all tested compound series. The compounds identified as active in the initial HTS underwent confirmation assays to determine minimum inhibitory concentration (MIC) and cytotoxicity, following established protocols. Confirmatory assays identified 33 hits (MIC <= 16 mu g/mL), with 78% effective at very low concentrations (<= 0.25 mu g/mL). Seven hits showed safety profiles against HEK-293 cells and red blood cells at concentrations below 32 mu g/mL. Based on a comparative analysis of their potency against pathogenic microorganisms and cell toxicity, the salts of triphenylphosphonium and quinolinium with linear C8 hydrocarbon substituents (compounds 1b and 5b, respectively), and isoquinolinium, methylpyridinium and triethylammonium with linear C18 hydrocarbon substituents (compounds 3g, 4g, and 7g, respectively) have emerged as the most promising candidates for microbial growth control.

Abstract Nitrocatechols are the standard pharmacophore to develop potent tight-binding inhibitors of catechol O-methyltransferase (COMT), which can be used as coadjuvant drugs to manage Parkinson's disease. Tolcapone is the most potent drug of this class, but it has raised safety concerns due to its potential to induce liver damage. Tolcapone-induced hepatotoxicity has been attributed to the nitrocatechol moiety; however, other nitrocatechol-based COMT inhibitors, such as entacapone, are safe and do not damage the liver. There is a knowledge gap concerning which mechanisms and chemical properties govern the toxicity of nitrocatechol-based COMT inhibitors. Using a vast array of cell-based assays, we found that tolcapone-induced toxicity is caused by direct interference with mitochondria that does not depend on bioactivation by P450. Our findings also suggest that (a) lipophilicity is a key property in the toxic potential of nitrocatechols; (b) the presence of a carbonyl group directly attached to the nitrocatechol ring seems to increase the reactivity of the molecule, and (c) the presence of cyano moiety in double bond stabilizes the reactivity decreasing the cytotoxicity. Altogether, the fine balance between lipophilicity and the chemical nature of the C1 substituents of the nitrocatechol ring may explain the difference in the toxicological behavior observed between tolcapone and entacapone.

Abstract Carbon electrodes, especially the glassy carbon electrodes (GCE) are widely accepted as very versatile sensing platforms. However, correlating the behaviour of the ferri/ferrocyanide redox couple ([Fe(CN) 6 ] 3-/4 ) with the GCE ' s surface modification is challenging. The surface modification can be achieved by applying a preconditioning electrochemical activation procedure. Hence, we report the investigation performed in order to provide further insights into the electrochemical behaviour of the commonly used redox probe in aqueous solutions. To that aim we took advantage of powerful and complementary electrochemical analytical techniques, like cyclic voltammetry (CV) and electrochemical impedance spectroscopy (EIS). Thus, this work highlights the critical role of the GCE initial conditions for optimizing the charge transfer processes and therefore to improve the [Fe(CN) 6 ] 3-/4- performance in sensing applications. The best results were obtained in phosphate buffer saline solution with previous electrochemical activation by fast potential cycling between [-0.5 and +1.8] V (vs. Ag| AgCl (KCl sat.)). Finally, one can consider this an eco-friendly and simple procedure to be carried out in the lab, however, its use must be carefully optimized when exploring other systems, as highlighted herein.

Abstract The present investigation describes the experimental evaluation of relevant physicochemical properties of five organochlorine compounds (OCs), including some that are related to their environmental mobility. The vapor pressures of (2,4′-Dichlorodiphenyl)dichloroethane (2,4′-DDD, CASN:53-19-0), 1,1-Dichloro-2,2-bis(4-chlorophenyl)ethane (4,4′-DDD, CASN:72-54-8) and 2,2-Bis(4-chlorophenyl)acetic acid (4,4′-DDA, CASN:83-05-6), as well as of the bactericide Nitrapyrin (CASN:1929-82-4) and of the rodenticide Crimidine (CASN:535-89-7) were determined at different temperatures. The Knudsen mass-loss effusion technique was employed to determine the sublimation vapor pressures of the referred compounds, apart from Crimidine. For the latter compound, a static method using a capacitance diaphragm manometer enabled the measurement of vapor pressures of both condensed (crystalline and liquid) phases. This technique was also used to measure the vapor pressures of the crystalline phase of Nitrapyrin over a larger temperature range, as well as its vaporization vapor pressures. The results of the standard molar enthalpies, entropies, and Gibbs energies of sublimation for all five compounds and of vaporization for Crimidine and Nitrapyrin, at reference temperatures, were derived. For these two compounds the phase diagram representations of the (p,T) results, in the vicinity of the triple point, were obtained. DSC analysis enabled the determination of the crystalline heat capacities of the five OCs studied and also of their temperatures and enthalpies of fusion. Gas-phase thermodynamic properties were estimated using quantum chemical calculations. The thermodynamic stability of the compounds studied was evaluated and compared in the crystalline and gaseous phases, at 298.15 K, in consideration with estimated results of the standard Gibbs energies of formation. Combined with other physical and chemical properties, the results derived from this study can be used to predict the mobility, and environmental fate of these pollutants. © 2024 Elsevier Ltd

Abstract The need to transition from fossil fuels to renewables arises from factors such as depletion, price fluctuations, and environmental considerations. Lignocellulosic biomass, being abundant, and quickly renewable, and not interfering with food supplies, offers a standout alternative for chemical production. This paper explores the energetic characteristics of two derivatives of furfural-a versatile chemical obtained from biomass with great potential for commercial sustainable chemical and fuel production. The standard (p degrees = 0.1 MPa) molar enthalpies of formation of the liquids furfurylamine and 5-methylfurfurylamine were derived from the standard molar energies of combustion, determined in oxygen and at T = 298.15 K, by static bomb combustion calorimetry. Their standard molar enthalpies of vaporization were also determined at the same temperature using high-temperature Calvet microcalorimetry. By combining these data, the gas-phase enthalpies of formation at T = 298.15 K were calculated as -(43.5 +/- 1.4) kJmol-1 for furfurylamine, and -(81.2 +/- 1.7) kJmol-1 for 5-methylfurfurylamine. Furthermore, a theoretical analysis using G3 level calculations was performed, comparing the calculated enthalpies of formation with the experimental values to validate both results. This method has been successfully applied to similar molecules. The discussion looks into substituent effects in terms of stability and compares them with similar compounds.

Abstract Given the growing scarcity of water and the continuous increase in emerging pollutants detected in water bodies, there is an imperative need to develop new, more effective, and sustainable treatments for wastewater. Advanced oxidation processes (AOPs) are considered a competitive technology for water treatment. Specifically, ozonation has received notable attention as a promising approach for degrading organic pollutants in wastewater. However, different groups of pollutants are hardly degradable via single ozonation. With continuous development, it has been shown that using engineered nanomaterials as nanocatalysts in catalytic ozonation can increase efficiency by turning this process into a low-selective AOP for pollutant degradation. Nanocatalysts promote ozone decomposition and form active free radicals responsible for increasing the degradation and mineralization of pollutants. This work reviews the performances of different nanomaterials as homogeneous and heterogeneous nanocatalysts in catalytic ozonation. This review focuses on applying metal- and carbon-based engineered nanomaterials as nanocatalysts in catalytic ozonation and on identifying the main future directions for using this type of AOP toward wastewater treatment.

Abstract The thermal behaviour of bathophenanthroline and bathocuproine has been studied using several techniques, namely, differential scanning calorimetry and thermogravimetry. To determine their respective enthalpies of sublimation, vapor pressure measurements were carried out using different methods, such as Knudsen effusion mass loss/mass spectrometry, isothermal thermogravimetry, and a quartz crystal microbalance technique. Furthermore, the enthalpies of sublimation were determined by measuring the heat change of the sublimation process using high-temperature Calvet microcalorimetry. The results obtained in this work allowed the determination of the standard molar enthalpies of sublimation at 298.15 K, for bathophenanthroline and bathocuproine. The values obtained were (183.8 +/- 2.2) kJ & sdot;mol- 1 and (206.2 +/- 2.8) kJ & sdot;mol- 1, respectively. Additionally, the standard molar enthalpies of fusion were determined to be (30.4 +/- 0.4) kJ & sdot;mol- 1 and (26.5 +/- 1.6) kJ & sdot;mol- 1 for bathophenanthroline and bathocuproine, respectively. The analysis of the results allows a deeper understanding of the phase transition behavior for these compounds from the condensed to the gaseous phases, elucidating molecular decomposition and the inherent intermolecular forces governing the species.

Abstract Urban agricultural soils have important social, environmental, and economic roles in big cities, contributing to their sustainability. However, food production in urban soils may be compromised due to soil pollution that resulted from decades of industrial, non-regulated environmental activity and mobile transport. In this study, 12 soils from the urban agricultural area of Rome (Italy) were analyzed for the potentially toxic elements (PTEs) Be, Ba, Pb, Co, Ni, V, Zn, Hg, Cd, As, Cu, and Cr. All but one of the soils under analysis were characterized by at least one PTE concentration above the threshold limit defined by the D.Lgs 152/06 for agricultural soils. Multivariate analysis showed that the soils could be classified into five clusters: clusters I and II had relatively lower mean PTE concentrations; clusters III, IV, and V had relatively higher mean PTE concentrations with several PTE concentrations above the threshold proposed by ILD. Three factors contributing to the variability of the PTE's concentration in the soils under investigation were identified: a geological factor related to PTE As, Ba, Be, and V; an anthropogenic factor related to Pb and Cu; and a mixed factor related to Co, Cr, Ni, and Zn. High PTE content may limit the utilization of urban soils for food production.