Publications

Abstract The discovery of effective drugs for the treatment of neurodegenerative disorders (NDs) is a deadlock. Due to their complex etiology and high heterogeneity, progresses in the development of novel NDs therapies have been slow, raising social/economic and medical concerns. Nanotechnology and nanomedicine evolved exponentially in recent years and presented a panoply of tools projected to improve diagnosis and treatment. Drug-loaded nanosystems, particularly nanoparticles (NPs), were successfully used to address numerous drug glitches, such as efficacy, bioavailability and safety. Polymeric nanoparticles (PNPs), mainly based on polylactic-co-glycolic acid (PLGA), have been already validated and approved for the treatment of cancer, neurologic dysfunctions and hormonal-related diseases. Despite promising no PNPs-based therapy for neurodegenerative disorders is available up to date. To stimulate the research in the area the studies performed so far with polylactic-co-glycolic acid (PLGA) nanoparticles as well as the techniques aimed to improve PNPs BBB permeability and drug targeting were revised. Bearing in mind NDs pharmacological therapy landscape huge efforts must be done in finding new therapeutic solutions along with the translation of the most promising results to the clinic, which hopefully will converge in the development of effective drugs in a foreseeable future.

Abstract Coumarin is a privilege scaffold in medicinal chemistry. Coumarin derivatives are still an emerging class of highly potent pharmaceutical drugs, best known in the field of antimicrobials and anticoagulants. Thiocoumarins are a particular class of coumarins in which one or two of the oxygen atoms are replaced by a sulfur. They are chemically subdivided in three groups: Thiocoumarins, 2-thioxocoumarins, and dithiocoumarins. This review emphasizes the rationale behind the synthesis and biological applications of the most relevant publications related to this family of compounds. Particular attention has been given to their potential as drug candidates, with particular emphasis in the last 5 years. This article is based on the most relevant information collected from multiple electronic databases, including SciFinder, Pubmed, Espacenet, and Mendeley.

Abstract Targeting antioxidants to mitochondria is considered a promising strategy to prevent cellular senescence and skin ageing. In this study, we investigate whether four hydroxybenzoic acid-based mitochondria-targeted antioxidants (MitoBENs, MB1-4) could be used as potential active ingredients to prevent senescence in skin cells. Firstly, we evaluated the chemical stability, cytotoxicity, genotoxicity and mitochondrial toxicity of all compounds. We followed this by testing the antioxidant protective capacity of the two less toxic compounds on human skin fibroblasts. We then assessed the effects of the best hit on senescence, inflammation and mitochondrial remodeling on a 3D skin cell model, while also testing its mutagenic potential. Cytotoxicity and mitochondrial toxicity rankings were produced: MB3 < MB4 similar or equal to MB1 < MB2 and MB3 < MB1 < MB4 < MB2, respectively. These results suggest that pyrogallol-based compounds (MB2 and MB4) have lower cytotoxicity. The pyrogallol derivative, MB2, containing a 6-carbon spacer, showed a more potent antioxidant protective activity against hydrogen peroxide cytotoxicity. In a 3D skin cell model, MB2 also decreased transcripts related to senescence. In sum, MB2's biological safety profile, good chemical stability and lack of mutagenicity, combined with its anti-senescence effect, converts MB2 into a good candidate for further development as an active ingredient for skin anti-ageing products.

Abstract Small-cell carcinoma of the ovary of hypercalcemic type (SCCOHT) and endometrial cancer from type 1 and type 2 are gynecological tumors that affect women worldwide. The treatment encompasses the use of cytotoxic drugs that are nonspecific and inefficient. Mitocans, a family of drugs that specifically target tumor cells' mitochondria, might be a solution, as they conjugate compounds, such as antioxidants, with carriers, such as lipophilic cations, that direct them to the mitochondria. In this study, caffeic acid was conjugated with triphenylphosphonium (TPP), 4-picolinium, or isoquinolinium, forming 3 new compounds (Mito6_TPP, Mito6_picol., and Mito6_isoq.) that were tested on ovarian (COV434) and endometrial (Hec50co and Ishikawa) cancer cells. The results of MTT and neutral red assays suggested a time- and concentration-dependent decrease in cell viability in all tumor cell lines. The presence of apoptosis was indicated by the Giemsa and Hoechst staining and by the decrease in mitochondrial membrane potential. The measurement of intracellular reactive oxygen species demonstrated the antioxidant properties of these compounds, which might be related to cell death. Generally, Mito6_TPP was more active at lower concentrations than Mito6_picol. or Mito6_isoq., but was accompanied by more cytotoxic effects, as shown by the lactate dehydrogenase release. Non-tumorous cells (HFF-1) showed no changes after treatment. This study assessed the potential of these compounds as anticancer agents, although further investigation is needed.

Abstract Adherence to topical treatments is low and is known to be influenced by the vehicle properties. Betamethasone dipropionate (BD) is an anti-inflammatory steroid, used in psoriasis treatment in the form of an ointment, cream, or solution. The aim of this work was to develop a new vehicle for BD, focusing on the preferences of patients with psoriasis as a strategy to improve treatment adherence. Two vehicles with an aqueous external phase were explored: an emulgel and a hydrogel based on a cyclodextrin inclusion complex used to improve the aqueous solubility of BD. Since BD solubilization was not fully achieved in the hydrogel, only the emulgel was selected for further characterization. This new vehicle (emulgel) is characterized by its white, shiny appearance and good spreading properties. In comparison with petrolatum, a lower residue, higher evaporation rate, lower stickiness, and reduced ability to stain polyester fabric were observed. This vehicle also showed shear thinning behavior. The impact of this new vehicle on adherence to topical treatments should be further confirmed in clinical settings.

Abstract Atorvastatin (ATV) is a statin member consumed in high quantities worldwide. In response to that, the occurrence of ATV in environmental waters has become a reality, highlighting the need of rapid and sensitive analytical devices for its monitoring. In this work, the first electrochemical molecularly imprinted polymer (MIP) sensor for the detection of ATV in water samples is presented. Computational studies were conducted based on quantum mechanical (QM) calculations and molecular dynamics (MD) simulations for rational selection of a suitable functional monomer and to study in detail the templatemonomer interaction, respectively. The sensor was prepared by electropolymerisation of the selected 4aminobenzoic acid (ABA) monomer with ATV, acting as template, on screen printed carbon electrode (SPCE). Cyclic voltammetry (CV) and electrochemical impedance spectroscopy (EIS) techniques were applied to characterise the modified electrode surfaces. The quantitative measurements were carried out with differential pulse voltammetry (DPV) in 0.1 M phosphate buffer (pH = 7). After investigation and optimisation of important experimental parameters, a linear working range down to 0.05 mmol L-1 was determined with a correlation coefficient of 0.9996 and a limit of detection (LOD) as low as 0.049 mmol L-1 (S/N = 3). High sensitivity and selectivity of the prepared sensor were demonstrated with the ability to recognise ATV molecules over its closer structural analogues. Moreover, the sensor was quickly and successfully applied in spiked water samples, proving its potential for future on-site monitoring of ATV in environmental waters.

Abstract A novel molecularly imprinted polymer (MIP) has been developed based on a simple and sustainable strategy for the selective determination of citalopram (CTL) using screen-printed carbon electrodes (SPCEs). The MIP layer was prepared by electrochemical in situ polymerization of the 3-amino-4 hydroxybenzoic acid (AHBA) functional monomer and CTL as a template molecule. To simulate the polymerization mixture and predict the most suitable ratio between the template and functional monomer, computational studies, namely molecular dynamics (MD) simulations, were carried out. During the experimental preparation process, essential parameters controlling the performance of the MIP sensor, including CTL:AHBA concentration, number of polymerization cycles, and square wave voltammetry (SWV) frequency were investigated and optimized. The electrochemical characteristics of the prepared MIP sensor were evaluated by both cyclic voltammetry (CV) and electrochemical impedance spectroscopy (EIS) techniques. Based on the optimal conditions, a linear electrochemical response of the sensor was obtained by SWV measurements from 0.1 to 1.25 mu mol L-1 with a limit of detection (LOD) of 0.162 mu mol L-1 (S/N = 3). Moreover, the MIP sensor revealed excellent CTL selectivity against very close analogues, as well as high imprinting factor of 22. Its applicability in spiked river water samples demonstrated its potential for adequate monitoring of CTL. This sensor offers a facile strategy to achieve portability while expressing a willingness to care for the environment.

Abstract This work describes the effect of potential and temperature on the grapheneionic liquid (EMImBF4) interfacial structure and properties with the focus on a novel phenomenon of ionic saturation. We apply classical molecular dynamics simulations to reproduce well-known phenomena of overscreening, mono -layer formation, and temperature-induced smearing of the interfacial structure. Using quantum density functional theory calculations, we show how quantum capacitance dampens the influence of temperature and improves the agreement with the experimental data. Using a bilayer model, we study characteristic features of capacitance-potential dependence and relate them to the changes in interfacial structure. These insights are of fundamental and practical importance for the application of similar interfaces in electrochemical energy storage and transformation devices such as capacitors and actuators. (C) 2022 The Authors. Published by Elsevier B.V.

Abstract Particulate matter (PM) and pollen interaction, either airborne or at the respiratory mucosa needs further clarification, as allergic reaction intensification can be related to the PM physical characteristics and toxicity. This study aimed to investigate the physical-chemical properties of PM that can adhere to the pollen wall during its transport or inhalation, using Quercus spp. as a model, in three Portuguese cities with different geographical locations, meteorological influ-ence and urbanization levels. Possible sources were evaluated through air masses trajectory analysis using the HYSPLIT model and correlation with meteorological factors. The sampling was performed using a 7-days Hirst-type volumetric sampler, and the pollen grains were observed using a Field Emission Electron Probe Microanalyser for PM analysis. A secondary electron image of each pollen grain was taken, to determine the adhered particles characteristics and energy dispersive x-ray spectroscopy (EDS) spectra were obtained for individual particles. A total of 484 pollen grains was observed, with 7683 particles counted and 1914 EDS spectra analyzed. The particle's equivalent diameter ranged from 0.3-16 mu m, with most having a diameter < 3 mu m. For the three cities, there were significant differences in the number of particles per pollen and the % area occupied by the particles. Particles adhered were mainly Si-rich, but variations in other dominant groups were observed. For Evora and Guarda, Ca-rich, SO-rich were second and third more representative, while Porto were Organic and Cl-rich. Metals&Oxides were found in all cities with the highest number in Porto. P-rich particles were only found in Evora. Sea salt particles were observed in Evora, coincide with air mass trajectories possible carrying them from the Mediterranean Sea. In conclusion, the PM physical characteristics are similar between the studied cities, however, the dominant chemical composition is different, certainly impacting the exposome influence and pollen-allergy intensification towards the same pollen type and concentration.

Abstract <jats:p> Ionic liquids (ILs) are a unique class of electrolytes, which characteristics make them suitable for use in solar cells, supercapacitors, and fuel cells<jats:sup>1</jats:sup>. Due to the appealing properties such as good electrochemical stability, low vapour pressure, high concentration of ions and the lack of solvent, they have been under intense study since the early 2000s. Although numerous theoretical<jats:sup>2,3</jats:sup>, computational<jats:sup>4,5</jats:sup>, and experimental studies<jats:sup>6,7</jats:sup> have shed light on the interfacial properties of ILs, which differ noticeably from the aqueous electrolytes, multiple open questions remain. One such problem is how the interfacial capacitance is affected by the ambient temperature, as studies have shown both positive and negative temperature dependences<jats:sup>8,9</jats:sup>. Understanding the temperature dependence of interfacial capacitance is crucial as it is relevant for the description of energy storage and is one of the few quantities, which can be estimated both experimentally and computationally.</jats:p> <jats:p>In this study, we combine the density functional theory (DFT) calculations with molecular dynamics (MD) simulations of graphene (Gr) | EMImBF<jats:sub>4</jats:sub> IL interface to explain the effect of temperature on capacitance. MD simulations allow us to investigate the probable distribution of ions near the electrode’s surface and relate the changes of ILs structure to the capacitance using the interfacial bilayer model (IBL). We show that the increase of temperature affects the capacitance near the potential of zero charge by attenuating the overscreening without a notable change in the IL interfacial structure. The characteristic peaks and plateaus in the capacitance potential dependence are explained through the concepts of IL layering and saturation of the second IL layer described in the IBL. Using the DFT calculations, we estimate the impact of the quantum capacitance of Gr on the total interfacial capacitance and its temperature dependence. By accounting for the limiting quantum capacitance, the total interfacial capacitance was significantly altered in the case of the Gr electrode, as the effect of the temperature was dampened, and a V-shaped capacitance curve was obtained.</jats:p> <jats:p>Acknowledgements:</jats:p> <jats:p>This work was supported by the Estonian Research Council grant PSG249 and by the EU through the European Regional Development Fund under project TK141 (2014-2020.4.01.15-0011). The financial support from FCT/MCTES through the Portuguese national funds, project No. UID/QUI/50006/2021 (LAQV@REQUIMTE) is also acknowledged.</jats:p> <jats:p>References:</jats:p> <jats:p>1 D. R. MacFarlane, N. Tachikawa, M. Forsyth, J. M. Pringle, P. C. Howlett, G. D. Elliott, J. H. Davis, M. Watanabe, P. Simon and C. A. Angell, <jats:italic>Energy Environ. Sci.</jats:italic>, 2014, <jats:bold>7</jats:bold>, 232–250.</jats:p> <jats:p>2 A. A. Kornyshev, <jats:italic>J. Phys. Chem. B</jats:italic>, 2007, <jats:bold>111</jats:bold>, 5545–5557.</jats:p> <jats:p>3 Z. A. H. Goodwin and A. A. Kornyshev, <jats:italic>Electrochem. Commun.</jats:italic>, 2017, <jats:bold>82</jats:bold>, 129–133.</jats:p> <jats:p>4 M. Salanne, <jats:italic>Phys. Chem. Chem. Phys.</jats:italic>, 2015, <jats:bold>17</jats:bold>, 14270–14279.</jats:p> <jats:p>5 I. V. Voroshylova, H. Ers, V. Koverga, B. Docampo-Álvarez, P. Pikma, V. B. Ivaništšev and M. N. D. S. Cordeiro, <jats:italic>Electrochim. Acta</jats:italic>, 2021, <jats:bold>379</jats:bold>, 138148.</jats:p> <jats:p>6 L. Siinor, K. Lust and E. Lust, <jats:italic>J. Electrochem. Soc.</jats:italic>, 2010, <jats:bold>157</jats:bold>, F83.</jats:p> <jats:p>7 V. Lockett, M. Horne, R. Sedev, T. Rodopoulos and J. Ralston, <jats:italic>Phys. Chem. Chem. Phys.</jats:italic>, 2010, <jats:bold>12</jats:bold>, 12499–12512.</jats:p> <jats:p>8 F. Silva, C. Gomes, M. Figueiredo, R. Costa, A. Martins and C. M. Pereira, <jats:italic>J. Electroanal. Chem.</jats:italic>, 2008, <jats:bold>622</jats:bold>, 153–160.</jats:p> <jats:p>9 M. Drüschler, N. Borisenko, J. Wallauer, C. Winter, B. Huber, F. Endres and B. Roling, <jats:italic>Phys. Chem. Chem. Phys.</jats:italic>, 2012, <jats:bold>14</jats:bold>, 5090–5099. </jats:p>