Publications

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 Patients with breast or ovarian cancer have not benefited from improved efficacy with pegylated liposomal doxorubicin relative to free drug, likely due to the limited extent of the enhanced permeability and retention (EPR) effect, further compromising drug bioavailability in the tumor. Herein it is hypothesized that targeting nucleolin overexpressed in tumor endothelial cells (readily accessible from the vascular compartment), besides cancer cells, with PEGASEMP (doxorubicin hydrochloride in a lipid-based pegylated nanoparticle functionalized with a 31-aminoacid peptide targeting nucleolin), lessens the dependence on high systemic exposures and EPR effect for successful tumor targeting. This strategy has resulted in improved intracellular tumor bioavailability of doxorubicin, at low systemic exposure, associated with a safe toxicological profile. Levels of cell surface nucleolin dictated the antitumor activity of PEGASEMP against nucleolin-overexpressing solid tumors of diverse histological origin, evidencing a significant growth inhibition of malignant mesothelioma over the standard of care. Those observations were paralleled by an impairment of the nucleolin-positive vasculature and downregulation of typically overexpressed genes. Patient stratification based on nucleolin mRNA expression correlated with prognosis and enabled identification of breast and mesothelioma tumors that may potentially benefit from PEGASEMP. Overall, a novel principle of drug delivery is presented with potential therapeutic impact across nucleolin-overexpressing human cancers. Data Availability: The data that support the findings of this study are available from the corresponding author upon reasonable request.

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.

Abstract Molecularly imprinted materials have been used in selective photocatalysis, essentially due to surface properties, possibility of reuse and low cost, that enhance their industrial and economic interest. The molecular imprinting technique allows the development of photocatalysts with selective recognition for a template molecule, used during synthesis, by increasing the surface area caused by selective recognition sites for the template used. In this work the preparation of hollow titania microspheres was merged with the process of generating selectivity for bilirubin in the shell structure by molecular imprinting. Three major synthesis parameters (solvent, temperature and TiO2 precursor) were studied by performing a set of experiments based in a full factorial design. The selected synthesis conditions were mainly dictated by the maximization of the surface area normalized by the thickness of the TiO2 shell and its controllability. The microspheres kept the integrity of the spherical shape while dispersed in the synthesis solvent. The observed imprinting features for the hollow microspheres prepared in the final synthesis conditions included imprinting factors of 3.1 for the binding strength and 1.3 for the capacity, and bilirubin/protoporphirin selectivity factors of 4.0 in terms of binding strength and 9.6 in terms of binding capacity. These features are very promising, especially the high selectivity factors, given the high resemblance between bilirubin and protoporphirin, and also due to the threat that the somewhat aggressive treatment for the silica core removal, might eventually pose to the templated microstructure of the shell. In fact, the photocatalytic selectivity of the imprinted microspheres was confirmed, with the observation of up to two-fold faster rates of bilirubin consumption vs. protoporphyrin consumption. © 2020

Abstract Two immunosensors were advanced to target hazelnut Cor a 14 based on electrochemical and optical transduction. Both approaches were developed with two types of custom-made antibodies, namely anti-Cor a 14 IgG (rabbit) and anti-Cor a 14 IgY (hen's egg) targeting the Cor a 14 allergen. Antibody immobilisation was performed via EDC/NHS onto disposable screen-printed electrodes. The detection limit (LOD) of the electrochemical immunoassay for Cor a 14 was 5-times lower than the optical, being down to 0.05 fg mL-1 with a dynamic range of 0.1 fg mL-1 to 0.01 ng mL-1. Antibody selectivity was verified against non-target 2S albumins (potential crossreactive plant species). Anti-Cor a 14 IgY exhibited the best specificity, presenting minor cross-reactivity with peanut/walnut. Preliminary results of the application of anti-Cor a 14 IgY electrochemical immunosensor to incurred foods established a LOD of 1 mg kg- 1 of hazelnut in wheat (0.16 mg kg- 1 hazelnut protein).

Abstract The urgent need to reduce the consumption of fossil fuels drives the demand for renewable energy and has been attracting the interest of the scientific community to develop materials with improved energy storage properties. We propose a sustainable route to produce nanoporous carbon materials with a high-surface area from commercial graphite using a dry ball-milling procedure through a systematic study of the effects of dry ball-milling conditions on the properties of the modified carbons. The microstructure and morphology of the dry ball-milled graphite/carbon composites are characterized by BET (Brunauer-Emmett-Teller) analysis, SEM (scanning electron microscopy), ATR-FTIR (attenuated total reflectance-Fourier transform infrared spectroscopy) and Raman spectroscopy. As both the electrode and electrolyte play a significant role in any electrochemical energy storage device, the gravimetric capacitance was measured for ball-milled material/glassy carbon (GC) composite electrodes in contact with a deep eutectic solvent (DES) containing choline chloride and ethylene glycol as hydrogen bond donor (HBD) in a 1:2 molar ratio. Electrochemical stability was tracked by measuring charge/discharge curves. Carbons with different specific surface areas were tested and the relationship between the calculated capacitance and the surface treatment method was established. A five-fold increase in gravimetric capacitance, 25.27 F center dot g(-1) (G40) against 5.45 F center dot g(-1), was found for commercial graphene in contact with DES. Optimal milling time to achieve a higher surface area was also established.

Abstract Carbon nanotubes (CNTs) are receiving special attention due to their remarkable thermal, electrical, and mechanical properties. The present work reports an innovative synthesis procedure to decorate MWCNTs with silver nanoparticles (Ag-NPs) via pulsed reverse deposition technique using a deep eutectic solvent (DES) based on choline chloride and glycerol as an electrolyte at room temperature, not requiring any previous surface modification of MWCNTs. MWCNTs decorated with Ag-NPs disclose a significant enhancement of their electrochemical performance as demonstrated by the increase of electrode stability and specific capacitance. Electrochemical characterization of the composite material was performed using cyclic voltammetry and charge/discharge curves, achieving a specific capacitance up to 28.50 F. g-1, against 4.70 F. g-1 for the commercial MWCNTs in a three-electrode system. Retention of the specific capacitance up to 99% for the Ag-MWCNTs composites compared with a value of 78% for electrodes modified with commercial MWCNTs. The Ag-MWCNTs composites were characterized through SEM/EDX analysis, ultrahighresolution STEM, in which the Z - Contrast image was collected, and Raman analysis to prove the successful attachment of the Ag-NPs to the MWCNTs surface. AFM was performed to evaluate the conductivity of the composites. (c) 2021 The Authors. Published by Elsevier B.V. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

Abstract Fuel cells are emerging devices as clean and renewable energy sources, provided their efficiency is increased. In this work, we prepared nanocomposites based on multiwalled carbon nanotubes (MWNTs) and transition metal dichalcogenides (TMDs), namely WS2 and MoS2, and evaluated their performance as electrocatalysts for the oxygen evolution reaction (OER) and the oxygen reduction reaction (ORR), relevant to fuel cells. The one- and two-dimensional (1D and 2D) building blocks were initially exfoliated and non-covalently functionalized by surfactants of opposite charge in aqueous media (tetradecyltrimethylammonium bromide, TTAB, for the nanotubes and sodium cholate, SC, for the dichalcogenides), and thereafter, the three-dimensional (3D) MoS2@MWNT and WS2@MWNT composites were assembled via surfactant-mediated electrostatic interactions. The nanocomposites were characterized by scanning electron microscopy (SEM) and structural differences were found. WS2@MWNT and MoS2@MWNT show moderate ORR performance with potential onsets of 0.71 and 0.73 V vs. RHE respectively, and diffusion-limiting current densities of -1.87 and -2.74 mA center dot cm(-2), respectively. Both materials present, however, better tolerance to methanol crossover when compared to Pt/C and good stability. Regarding OER performance, MoS2@MWNT exhibits promising results, with eta(10) and j(max) of 0.55 V and 17.96 mA center dot cm(-2), respectively. The fabrication method presented here is cost-effective, robust and versatile, opening the doors for the optimization of electrocatalysts' performance.

Abstract Aqueous surfactant/polymermixtures form colloidal structures of great fundamental interest and practical relevance, such as nanostructured hydrogels for biomedical and pharmaceutical uses. In this work, we investigated the phase behavior, structure and cytotoxicity of mixtures of a double-tailed lysine-based surfactant, 16Lys12, and two hydroxyethyl cellulose (HEC) derivatives, JR400 and LM200. The surfactant, S-, is anionic and self-assembles into tubular structures at room temperature, undergoing a tubule-to-vesicle transition at approximate to 44 degrees C. JR400 is a cationic homopolymer, P+, longer and more densely charged than LM200, a closely related hydrophobically modified polymer, HMP+. Electrostatic and hydrophobic interactions play a crucial role in the observed phase behavior and resulting colloidal structures. Both the S-/P+ and S-/HMP+ mixtures show three main phase regions: at surfactant charge excess, bluish dispersions containing mixed polymer/tubular aggregates and, upon heating, polymer/vesicle clusters; a white precipitate near charge equimolarity, coexisting with either a solution or a gel; and highly viscous hydrogels, at polymer charge excess. In the bluish dispersions, the S-/P+ and S-/HMP+ systems show relevant differences in thermal behavior and type of aggregates present. Cryogenic scanning electron microscopy shows that the hydrogels consist of honeycomb-like structure of surfactant and polymer moieties. Cytotoxicity assays in the bluish dispersion region indicate good levels of cytocompatibility for both types of surfactant/polymer systems. Overall, these dispersions and hydrogels can be further explored for the encapsulation and temperature-triggered release of biomolecules.

Abstract Most applications of nanocarbons, such as carbon nanotubes and graphene, require that they are well-separated and well-dispersed in a liquid phase. Intensive efforts have been put on exfoliating and dispersing nanocarbons in aqueous solvents, typically using amphiphilic dispersants and sonication/centrifugation procedures, alongside a drive to fundamentally understand and rationally optimize these processes. Herein, we employed a robust method to separate and disperse multiwalled carbon nanotubes (MWNTs), and graphene nanoplatelets (GnPs) either from bulk graphite or from pre-formed GnP powders, using rigorously controlled processing conditions. An ionic (sodium cholate) and a nonionic (Triton X-100) surfactant were used as dispersants. Our aim was to determine high-precision dispersibility curves (concentration of dispersed nanomaterial versus initial surfactant concentration) for the different nanocarbon/dispersant systems, characterize morphologically the dispersed particles and compare the mechanisms of exfoliation of 1D and 2D nanocarbons at molecular level. Typically bell-shaped dispersibility curves with a plateau were obtained, and from the latter several quantitative metrics were extracted that permitted reliable comparisons between nanocarbon/surfactant systems. Scanning electron and atomic force microscopies allowed to characterize the suspended particles in the as-obtained dispersions, namely the MWNT bundle width and GnP dimensions (mean lateral size and layer number). Under fixed conditions (in particular, delivered energy per carbon mass), MWNTs are dispersed in much higher yields, by two orders of magnitude, than GnPs. However, and significantly, a master curve for the dispersibility was obtained, implying that common fundamental features underpin the dispersing process, irrespective of nanocarbon (1D or 2D) or surfactant (ionic or nonionic) types.