Publications

Abstract Pesticides affect different organs and tissues according to their bioavailability, chemical properties and further molecular interactions. In animal models exposed to several classes of pesticides, neurotoxic effects have been described, including the reduction of acetylcholinesterase activity in tissue homogenates. However, in homogenates, the reduction in enzymatic activity may also result from lower enzymatic expression and not only from enzymatic inhibition. Thus, in this work, we aimed to investigate the neurotoxic potential of four distinct pesticides: glyphosate (herbicide), imazalil (fungicide), imidacloprid (neonicotinoid insecticide) and lambda-cyhalothrin (pyrethroid insecticide), by assessing their inhibitory effect on the activity of acetylcholinesterase (AChE), butyrylcholinesterase (BChE) and tyrosinase, by using direct in vitro enzymatic inhibition methods. All pesticides dose-dependently inhibited AChE activity, with an inhibition of 11 +/- 2% for glyphosate, 48 +/- 2% for imidacloprid, 49 +/- 3% for imazalil and 50 +/- 3% for lambda-cyhalothrin, at 1 mM. Only imazalil inhibited BChE. Imazalil induced dose-dependent inhibition of BChE with identical pattern as that observed for AChE; however, for lower concentrations (up to 500 mu M), imazalil showed higher specificity for AChE, and for higher concentrations, the same specificity was found. Imazalil, at 1 mM, inhibited the activity of BChE by 49 +/- 1%. None of the pesticides, up to 1 mM, inhibited tyrosinase activity. In conclusion, the herbicide glyphosate shows specificity for AChE but low inhibitory capacity, the insecticides imidacloprid and lambda-cyhalothrin present selective AChE inhibition, while the fungicide IMZ is a broad-spectrum cholinesterase inhibitor capable of inhibiting AChE and BChE in an equal manner. Among these pesticides, the insecticides and the fungicide are the ones with higher neurotoxic potential.

Abstract In this work, three pesticides of different physicochemical properties: glyphosate (GLY, herbicide), imidacloprid (IMD, insecticide), and imazalil (IMZ, fungicide), were selected to assess their cytotoxicity against Caco-2 and HepG2 cells. Cell viability was assessed by the Alamar Blue assay, after 24 and 48 h exposure to different concentrations, and IC50 values were calculated. The mechanisms underlying toxicity, namely cellular reactive oxygen species (ROS), glutathione (GSH) content, lipid peroxidation, loss of mitochondrial membrane potential (MMP), and apoptosis/necrosis induction were assessed by flow cytometry. Cytotoxic profiles were further correlated with the molecular physicochemical parameters of pesticides, namely: water solubility, partition coefficient in an n-octanol/water (Log P-ow) system, topological polar surface area (TPSA), the number of hydrogen-bonds (donor/acceptor), and rotatable bonds. In vitro outputs resulted in the following toxicity level: IMZ (Caco-2: IC50 = 253.5 +/- 3.37 mu M, and HepG2: IC50 = 94 +/- 12 mu M) > IMD (Caco-2: IC50 > 1 mM and HepG2: IC50 = 624 +/- 24 mu M) > GLY (IC50 >>1 mM, both cell lines), after 24 h treatment, being toxicity time-dependent (lower IC50 values at 48 h). Toxicity is explained by oxidative stress, as IMZ induced a higher intracellular ROS increase and lipid peroxidation, followed by IMD, while GLY did not change these markers. However, the three pesticides induced loss of MMP in HepG2 cells while in Caco-2 cells only IMZ produced significant MMP loss. Increased ROS and loss of MMP promoted apoptosis in Caco-2 cells subjected to IMZ, and in HepG2 cells exposed to IMD and IMZ, as assessed by Annexin-V/PI. The toxicity profile of pesticides is directly correlated with their Log P-ow, as affinity for the lipophilic environment favours interaction with cell membranes governs, and is inversely correlated with their TPSA; however, membrane permeation is favoured by lower TPSA. IMZ presents the best molecular properties for membrane interaction and cell permeation, i.e., higher Log P-ow, lower TPSA and lower hydrogen-bond (H-bond) donor/acceptor correlating with its higher toxicity. In conclusion, molecular physicochemical factors such as Log P-ow, TPSA, and H-bond are likely to be directly correlated with pesticide-induced toxicity, thus they are key factors to potentially predict the toxicity of other compounds.

Abstract In this work, three pesticides of different physicochemical properties, namely, glyphosate (herbicide), imidacloprid (insecticide) and imazalil (fungicide), were selected to assess their cytotoxicity against distinct cell models (Caco-2, HepG2, A431, HaCaT, SK-MEL-5 and RAW 264.7 cells) to mimic gastrointestinal and skin exposure with potential systemic effect. Cells were subjected to different concentrations of selected pesticides for 24 h or 48 h. Cell viability was assessed by Alamar Blue assay, morphological changes by bright-field microscopy and the IC50 values were calculated. Cytotoxic profiles were analysed using the physico-chemical parameters of the pesticides, namely: molecular weight, water solubility, the partition coefficient in the n-octanol/water (Log P-ow) system, the topological polar surface area (TPSA), and number of hydrogen-bonds (donor/acceptor) and rotatable bonds. Results showed that glyphosate did not reduce cell viability (up to 1 mM), imidacloprid induced moderate toxicity (IC50 > 1 mM for Caco-2 cells while IC50 = 305.9 +/- 22.4 mu M for RAW 264.7 cells) and imazalil was highly cytotoxic (IC50 > 253.5 +/- 3.37 for Caco-2 cells while IC50 = 31.3 +/- 2.7 mu M for RAW 264.7 cells) after 24 h exposure. Toxicity was time-dependent as IC50 values at 48 h exposure were lower, and decrease in cell viability was accompanied by changes in cell morphology. Pesticides toxicity was found to be directly proportional with their Log P-ow, indicating that the affinity to a lipophilic environment such as the cell membranes governs their toxicity. Toxicity is inverse to pesticides TPSA, but lower TPSA favours membrane permeation. The lower toxicity against Caco-2 cells was attributed to the physiology and metabolism of cell barriers equipped with various ABC transporters. In conclusion, physicochemical factors such as Log P-ow, TPSA and H-bond are likely to be directly correlated with pesticide-induced toxicity, thus being key factors to potentially predict the toxicity of other compounds.

Abstract A new (bio)sensing platform based on differential refractometric measurements was developed. The sensing scheme is based on the combination LPFGs/MIP/NIP, involving a dual channel system for real-time compensation of non-specific interactions. The correction system improves the sensor behavior by reducing the response to interferents by 30%. © 2022 The Author(s).

Abstract <jats:p>Fullerenes are reactive as dienophiles in Diels–Alder reactions. Their distinctive molecular shape and properties result in interesting and sometimes elusive reaction patterns. Herein, to contribute to the understanding of fullerene reactivity, we evaluate the energies of reactions for Diels–Alder cycloadditions of C60, C70, and IC60MA with anthracene (Ant), by means of DFT computational analysis in vacuum and solution. The methods used showed little differentiation between the reactivity of the different fullerenes. The C70-Ant adducts where addition takes place near the edge of the fullerene were found to be the most stable regioisomers. For the IC60MA-Ant adducts, the calculated energies of reaction increase in the order: equatorial &gt; trans-3 &gt; trans-2 ≈ trans-4 ≈ trans-1 &gt; cis-3 &gt; cis-2. The change in the functional suggests the existence of stabilizing dispersive interactions between the surface of the fullerene and the addends. HOMA (harmonic oscillator model of aromaticity) analysis indicated an increase in aromaticity in the fullerene hexagons adjacent to the bonded addend. This increase is bigger in the rings of bisadduct isomers that are simultaneously adjacent to both addends, which helps explain the extra stability of the equatorial isomers. Solvation by m-xylene decreases the exothermicity of the reactions studied but has little distinguishing effect on the possible isomers. Thermal corrections reduce the exothermicity of the reactions by ~10 kJ∙mol−1.</jats:p>

Abstract This work reports a comprehensive experimental evaluation of the solid-liquid-gas phase equilibria for five representative phenylene-thiophene co-oligomers (3-ring aromatic compounds having both phenyl and thienyl units). The melting temperatures and corresponding standard molar enthalpies and entropies of fusion were measured by differential scanning calorimetry. The equilibrium vapor pressures of the crystalline solids as a function of temperature were measured by a combined Knudsen/quartz-crystal effusion method, with the consequent derivation of the standard molar enthalpies, entropies, and Gibbs energies of sublimation. The thermodynamic properties of vaporization were estimated from the fusion and sublimation data. The results were analyzed together with the literature data for the corresponding phenylene and thiophene homo-oligomers. The thermodynamic properties of fusion and sublimation exhibited a dependence on ring identity and position that cannot be adequately described by a simple group additivity reasoning. The plot of the Gibbs energy of sublimation as a function of the number of thienyl rings in the co-oligomer showed the existence of two series. Terminal 3-thienyl rings and a linear molecular shape were found to be consistent factors contributing to the stabilization of the crystal phase. The higher melting temperatures and lower volatilities of crystalline 3-thienyl compounds were tentatively explained by the ability of these rings to maximize intermolecular C-H & BULL;& BULL;& BULL;pi interactions independently of the sulfur position. The optical energy gaps, as measured by UV-vis in solution, were found to lie within the values for typical organic semiconductors (< 4 eV) and to decrease for co-oligomers containing more 2-thienyl units, following the increased ring-ring planarity of the molecules. The surface morphology of vapor-deposited thin films suggests a stronger tendency of the co-oligomers, if compared to their corresponding homo-oligomers p-terphenyl and terthiophene, to form less amorphous films.

Abstract Surgical site infections (SSIs) are common postoperative occurrences due to contamination of the surgical wound or implanted medical devices with community or hospital-acquired microorganisms, as well as other endogenous opportunistic microbes. Despite numerous rules and guidelines applied to prevent these infections, SSI rates are considerably high, constituting a threat to the healthcare system in terms of morbidity, prolonged hospitalization, and death. Approximately 80% of human SSIs, including chronic wound infections, are related to biofilm-forming bacteria. Biofilm-associated SSIs are extremely difficult to treat with conventional antibiotics due to several tolerance mechanisms provided by the multidrug-resistant bacteria, usually arranged as polymicrobial communities. In this review, novel strategies to control, i.e., prevent and eradicate, biofilms in SSIs are presented and discussed, focusing mainly on two attractive approaches: the use of nanotechnology-based composites and natural plant-based products. An overview of new therapeutic agents and strategic approaches to control epidemic multidrug-resistant pathogenic microorganisms, particularly when biofilms are present, is provided alongside other combinatorial approaches as attempts to obtain synergistic effects with conventional antibiotics and restore their efficacy to treat biofilm-mediated SSIs. Some detection and real-time monitoring systems to improve biofilm control strategies and diagnosis of human infections are also discussed.

Abstract Covering: 2009 to 2021 Antimicrobial resistance is now rising to dangerously high levels in all parts of the world, threatening the treatment of an ever-increasing range of infectious diseases. This has becoming a serious public health problem, especially due to the emergence of multidrug-resistance among clinically important bacterial species and their ability to form biofilms. In addition, current anti-infective therapies have low efficacy in the treatment of biofilm-related infections, leading to recurrence, chronicity, and increased morbidity and mortality. Therefore, it is necessary to search for innovative strategies/antibacterial agents capable of overcoming the limitations of conventional antibiotics. Natural compounds, in particular those obtained from plants, have been exhibiting promising properties in this field. Plant secondary metabolites (phytochemicals) can act as antibiofilm agents through different mechanisms of action from the available antibiotics (inhibition of quorum-sensing, motility, adhesion, and reactive oxygen species production, among others). The combination of different phytochemicals and antibiotics have revealed synergistic or additive effects in biofilm control. This review aims to bring together the most relevant reports on the antibiofilm properties of phytochemicals, as well as insights into their structure and mechanistic action against bacterial pathogens, spanning December 2008 to December 2021.

Abstract The development of energy storage devices with better performance relies on the use of innovative materials and electrolytes, aiming to reduce the carbon footprint through the screening of low toxicity electrolytes and solvent-free electrode design protocols. The application of nanostructured carbon materials with high specific surface area, to prepare composite electrodes, is being considered as a promising starting point towards improving the power and energy efficiency of energy storage devices. Non-aqueous electrolytes synthesized using greener approaches with lower environmental impact make deep eutectic solvents (DES) promising alternatives for electrochemical energy storage and conversion applications. Accordingly, this work proposes a systematic study on the effect of the composition of DES containing a diol and an amide as HBD (hydrogen bond donor: 1,2-propylene glycol and urea), on the electrochemical performance of graphene and graphite composite electrodes/DES electrolyte interface. Glassy carbon (GC) was selected as the bare electrode material substrate to prepare the composite formulations since it provides an electrochemically reproducible surface. Gravimetric capacitance was measured for commercial graphene and commercial graphite/GC composite electrodes in contact with choline chloride, complexed with 1,2-propylene glycol, and urea as the HBD in 1:2 molar ratio. The electrochemical stability was followed by assessing the charge/discharge curves at 1, 2, and 4 A g−1. For comparison purposes, a parallel study was performed using commercial graphite. A four-fold increase in gravimetric capacitance was obtained when replacing commercial graphite (1.70 F g−1) by commercial graphene (6.19 F g−1) in contact with 1,2-propylene glycol-based DES. When using urea based DES no significant change in gravimetric capacitance was observed when commercial graphite is replaced by commercial graphene.