Publications

Abstract Deep eutectic solvents (DES) are often regarded as greener sustainable alternative solvents and are currently employed in many industrial applications on a large scale. Bearing in mind the industrial importance of DES-and because the vast majority of DES has yet to be synthesized-the development of cheminformatic models and tools efficiently profiling their density becomes essential. In this work, after rigorous validation, quantitative structure-property relationship (QSPR) models were proposed for use in estimating the density of a wide variety of DES. These models were based on a modelling dataset previously employed for constructing thermodynamic models for the same endpoint. The best QSPR models were robust and sound, performing well on an external validation set (set up with recently reported experimental density data of DES). Furthermore, the results revealed structural features that could play crucial roles in ruling DES density. Then, intelligent consensus prediction was employed to develop a consensus model with improved predictive accuracy. All models were derived using publicly available tools to facilitate easy reproducibility of the proposed methodology. Future work may involve setting up reliable, interpretable cheminformatic models for other thermodynamic properties of DES and guiding the design of these solvents for applications.</p>

Abstract This study aims to design and characterize Nanostructured lipid carriers (NLC) and Nanostructured lipid carrier-based hydrogels with Passiflora edulis seeds oil, a by-product from Madeira Island food industry. NLC were prepared by the ultrasonication technique, using passion fruit seeds oil as a liquid lipid and glyceryl distearate as a solid lipid. These NLC were then gelled with Poly (acrylic acid). Long-term stability studies were conducted with NLC and NLC-based hydrogels stored for 12 months. The following tests were performed: morphology, encapsulation efficiency, particle size analysis, polydispersity index analysis, zeta potential, pH measurement, color analysis, viscosity studies, texture analysis, in vitro occlusion test, ex vivo skin penetration study, tyrosinase inhibition activity, in vitro skin permeation experiments and in vitro cytotoxicity studies. The developed NLC had spherical shape and narrow particle sizes distribution with mean sizes in the range of 150 nm and PDI below 0.3, Zeta potential values around -30 mV and high Encapsulation efficiency. The tyrosinase inhibitory activity and skin retention of the nanoparticles was superior to that of the non-encapsulated oil. The developed formulations did not show cytotoxicity towards HaCat cells and presented suitable viscosity and texture properties for skin application, proving to be good candidates as depigmenting agent.

Abstract Determination of antibiotics in environmental waters is an important global issue. Although furazolidone (FZD) was banned from use in food-producing animals, owing to its mutagenic and carcinogenic effects, this antibiotic has been illegally used across the world and its presence in environment have being noted. In this work, the first selective molecularly imprinted polymer (MIP) was developed for electrochemical detection of FZD. It was constructed based on the modification of the traditional carbon paste electrode (CPE) with MIP microparticles, followed by introduction of multi-walled carbon nanotubes (MWCNTs). Quantum mechanical (QM) calculations and molecular dynamics (MD) simulations were performed to allow rational selection of an appropriate functional monomer and to simulate the best pre-polymerisation conditions, respectively. The MIP were synthetized by polymerization using 2-acrylamido-2-methyl-1-propanesulfonic acid (AMPS) as monomer and FZD as template molecule. The MIP microparticles were then incorporated on CPE-MWCNTs and the electrochemical analysis of FZD were evaluated by differential pulse voltammetry (DPV). After optimisation of experimental conditions, the MIP-CPE-MWCNTs sensor exhibited a good linear response over the concentration range of 0.01 mu M to 1 mu M with a correlation coefficient of 0.9995. The limit of detection (LOD) was found to be 0.03 mu M (S/N = 3). Due to high imprinting efficiency the sensor displayed selectivity to recognise FZD molecules and it was successfully applied in water samples where excellent recovery values (over 90 %) were obtained. The proposed sensor provides an efficient and promising sustainable strategy for monitorisation of FZD in environmental waters.

Abstract The applicability of deep eutectic solvents is determined by their physicochemical properties. In turn, the properties of eutectic mixtures are the result of the components' molar ratio and chemical composition. Owing to the relatively low viscosities displayed by alcohol-based deep eutectic solvents (DESs), their application in industry is more appealing. Modeling the composition-property relationships established in polyalcohol-based mixtures is crucial for both understanding and predicting their behavior. In this work, a physicochemical property-structure comparison study is made between four choline chloride polyalcohol-based DESs, namely, ethaline, propeline, propaneline, and glyceline. Physicochemical properties obtained from molecular dynamic simulations are compared to experimental data, whenever possible. The simulations cover the temperature range from 298.15 to 348.15 K. The simulated and literature experimental data are generally in good agreement for all the studied DESs. Structural properties, such as radial and spatial distribution functions, coordination numbers, hydrogen bond donor (HBD)-HBD aggregate formation, and hydrogen bonding are analyzed in detail. The higher prevalence of HBD:HBD and HBD:anion hydrogen bonds is likely to be the major reason for the relatively high density and viscosity of glyceline as well as for lower DES self-diffusions.

Abstract Amitriptyline (AMT) frequent presence in environmental waters reflects the continuous consumption growth and raises issues on the importance of its monitorization. In this work, a sensitive and selective electrochemiluminescence (ECL) sensor was constructed using molecularly imprinted polymer (MIP) recognition element for AMT detection. Molecular dynamics (MD) simulations were performed to select the best functional monomer. Precipitation polymerization was followed to prepare the MIP micro spheres using methacrylic acid (MAA) as functional monomer, ethylene glycol methacrylate (EGDMA) as crosslinker and chloroform (CHL) as solvent. The MIP sensor was then prepared on a low cost and disposable screen-printed electrodes (SPCEs), previously modified with single-walled carbon nanotubes (SWCNTs), by drop coating a solution containing the MIP microspheres synthesized. The mechanism of detection was based in the system Ru(bpy)(3)(2+)/AMT, where AMT acts as co-reactor of Ru(bpy)(3)(2+) ECL. Several parameters controlling the preparation process of the sensor and AMT detection were optimised. The MIP/SWCNTs/SPCE ECL sensor showed good analytical performance with a linear correlation between ECL signal and the AMT concentration ranging from 0.1 to 200 mu M (R-2 = 0.9991). The limits of detection (LOD) and quantification (LOQ) were found to be 0.4 mu M (S/N = 3) and 1.5 mu M (S/N = 10), respectively. The MIP ECL sensor displayed good selectivity to recognise AMT molecules when compared with analoge structures and it was successfully applied in real water samples with good recovery values (90 to 112%). The developed MIP ECL sensor is suitable for integration with portable devices for AMT detection in environmental waters.

Abstract 2.3. Cell culture conditions Skin fibroblasts from five sporadic late-onset PD (sPD) male patients and five age- and sex-matched healthy controls were obtained from a cell line repository of the Coriell Institute for Medical Research, USA (www.coriell.org), and their detailed information was previously described [43]. The repository ID numbers of control fibroblasts used were: ND29178, ND29179, ND34770, ND35044, and ND38530; the repository ID numbers of sPD fibroblasts used were: ND34265, ND35320, ND35322, ND35976, and ND39999.

Abstract A combination of several pharmacophores in one molecule has been successfully used for multi-target-directed ligands (MTDL) design. New propargylamine substituted derivatives combined with salicylic and cinnamic scaffolds were designed and synthesized as potential cholinesterases and monoamine oxidases (MAOs) inhibitors. They were evaluated in vitro for inhibition of acetyl- (AChE) and butyrylcholinesterase (BuChE) using Ellman's method. All the compounds act as dual inhibitors. Most of the derivatives are stronger inhibitors of AChE, the best activity showed 5-bromo-N-(prop-2-yn-1-yl)salicylamide 1e (IC50 = 8.05 mu M). Carbamates (4-bromo-2[(prop-2-yn-1-yl)carbamoyl]phenyl ethyl(methyl)carbamate 2d and 2,4-dibromo-6-[(prop-2-yn-1-yl)carbamoyl] phenyl ethyl(methyl)carbamate 2e were selective and the most active for BuChE (25.10 and 26.09 mu M). 4-Bromo2-[(prop-2-yn-1-ylimino)methyl]phenol 4a was the most potent inhibitor of MAOs (IC50 of 3.95 and approximate to 10 mu M for MAO-B and MAO-A, respectively) along with a balanced inhibition of both cholinesterases being a real MTDL. The mechanism of action was proposed, and binding modes of the hits were studied by molecular docking on human enzymes. Some of the derivatives also exhibited antioxidant properties. In silico prediction of physicochemical parameters affirm that the molecules would be active after oral administration and able to reach brain tissue.

Abstract Mobile handheld devices, such as smartphones and tablets, have become some of the most prominent ubiquitous terminals within the information and communication technology landscape. Their transformative power within the digital music domain changed the music ecosystem from production to distribution and consumption. Of interest here is the ever-expanding number of mobile music applications. Despite their growing popularity, their design in terms of interaction perception and control is highly arbitrary. It remains poorly addressed in related literature and lacks a clear, systematized approach. In this context, our paper aims to provide the first steps towards defining guidelines for optimal sonic interaction design practices in mobile music applications. Our design approach is informed by user data in appropriating mobile handheld devices. We conducted an experiment to learn links between control gestures and musical parameters, such as pitch, duration, and amplitude. A twofold action-reflection protocol and tool-set for evaluating the aforementioned links-are also proposed. The results collected from the experiment show statistically significant trends in pitch and duration control gesture mappings. On the other hand, amplitude appears to elicit a more diverse mapping approach, showing no definitive trend in this experiment.

Abstract 4-Oxoquinoline derivatives have been often used in drug discovery programs due to their pharmacological properties. Inspired on chromone and 4-oxoquinoline chemical structure similarity, a small series of quinoline-based compounds was obtained and screened, for the first time, toward human monoamine oxidases isoforms. The data showed the N-(3,4-dichlorophenyl)-1-methyl-4-oxo-1,4-dihydroquinoline-3-carboxamide 10 was the most potent and selective MAO-B inhibitor (IC50 = 5.30 +/- 0.74 nM and SI: >= 1887). The data analysis showed that prototropic tautomerism markedly influences the biological activity. The unequivocal characterisation of the quinoline tautomers was performed to understand the attained data. To our knowledge, there have been no prior reports on the characterisation of quinolone tautomers by 2D NMR techniques, namely by H-1-N-15 HSQC and H-1-N-15 HMBC, which are proposed as expedite tools for medicinal chemistry campaigns. Computational studies on enzyme-ligand complexes, obtained after MM-GBSA calculations and molecular dynamics simulations, supported the experimental data.

Abstract Chromone-3-phenylcarboxamides (Crom-1 and Crom-2) were identified as potent, selective, and reversible inhibitors of human monoamine oxidase B (hMAO-B). Since they exhibit some absorption, distribution, metabolism, and excretion (ADME)-toxicity liabilities, new derivatives were synthesized to map the chemical structural features that compose the pharmacophore, a process vital for lead optimization. Structure-activity relationship data, supported by molecular docking studies, provided a rationale for the contribution of the heterocycle's rigidity, the carbonyl group, and the benzopyran heteroatom for hMAO-B inhibitory activity. From the study, N-(3-chlorophenyl)-4H-thiochromone-3-carboxamide (31) (hMAO-B IC50 = 1.52 +/- 0.15 nM) emerged as a reversible tight binding inhibitor with an improved pharmacological profile. In in vitro ADME-toxicity studies, compound 31 showed a safe cytotoxicity profile in Caco-2, SH-SY5Y, HUVEC, HEK-293, and MCF-7 cells, did not present cardiotoxic effects, and did not affect P-gp transport activity. Compound 31 also protected SH-SY5Y cells from iron(III)-induced damage. Collectively, these studies highlighted compound 31 as the first-in-class and a suitable candidate for in vivo preclinical investigation.