Publications

Abstract The standard (p degrees =0.1 MPa) molar enthalpies of formation of orotic and isoorotic acids, in the crystalline phase, were derived from the respective standard massic energies of combustion measured by static bomb combustion calorimetry, in oxygen, at T = 298.15 K, as -821.7 +/- 1.1 kJ mol(-1) and -838.3 +/- 1.9 kJ mol(-1), respectively. The molecular structure and conformational behaviour of orotic and isoorotic acids were studied by theoretical calculations and the standard gas-phase molar enthalpies of formation were derived using an appropriate set of working reactions. Sublimation enthalpies, at the reference temperature T = 298.15 K, were estimated from difference between crystalline and gaseous enthalpies of formation and from statistically-based interaction indices derived from molecular surface electrostatic potentials.

Abstract Relevant thermochemical data of γ-butyrolactone (GBL), a compound of considerable industrial and environmental significance, obtained from experimental and computational studies are reported in this work. The standard (p° = 0.1 MPa) molar enthalpy of formation, at T = 298.15 K, in the gaseous phase, was determined from the enthalpy of combustion and vaporization, obtained by static bomb calorimetry in oxygen and by Calvet microcalorimetry, respectively. The enthalpy of formation in the gaseous phase was also determined from G3 calculations. The excellent agreement between the experimental and computational thermochemical data provided a critical literature review of GBL and the proposal of new reference values for this lactone. Copyright © 2020 American Chemical Society.

Abstract Featured Application This is a contribution for enlarging the thermodynamic database of organic compounds and ketone derivatives. These data are very relevant to controlling experimental investigations to produce value-added chemical products from biomass. Moreover, the knowledge from such data can be used in the development of schemes for the prediction of homologous properties of related compounds, in particular, modeling studies for the prediction of bio-oil composition. The energetic study of 6-hydroxy-1-indanone and 7-hydroxy-1-indanone was performed using experimental techniques and computational calculations. The enthalpies of combustion and sublimation of the two compounds were determined and allowed to derive the corresponding gas-phase standard molar enthalpies of formation. For this purpose, static-bomb combustion calorimetry and drop-method Calvet microcalorimetry were the experimental techniques used. Further, the enthalpy of fusion of each compound was obtained from scanning differential calorimetry measurements. Additionally, the gas-phase standard molar enthalpies of formation of these compounds were calculated through high-level ab initio calculations. The computational study of the molecular structures of the indanones was carried out and two possible conformers were observed for 6-hydroxy-1-indanone. Furthermore, the energetic effects associated with the presence of one hydroxyl group as a substituent on the benzenic ring of 1-indanone were also evaluated. Both experimental and theoretical methods show that 7-hydroxy-1-indanone is thermodynamically more stable than the 6-isomer in the gaseous phase and these results provide evidence for the existence of a strong intramolecular H-bond in 7-hydroxy-1-indanone. Finally, the intramolecular proton transfer in 7-hydroxy-1-indanone has been evaluated and as expected, it is not energetically favorable.

Abstract This article sums up three case studies carried out at a Portuguese science center, an elementary school, and a preschool, where storytelling and hands-on activities were combined. These studies produced indicators in line with the idea that appropriate and carefully chosen stories, combined with hands-on activities, may be a useful pedagogical approach to promote the attraction of young students to science and to teach some of its concepts. The hands-on activities, related to prior storytelling, seem to be a good way to involve students through listening, reading, imagining, understanding, making, and explaining, and thus can generate interest in science and scientific research. Furthermore, it is necessary to make a deeper assessment of the impact of those approaches on learning, development of scientific literacy, and the way young students perceive chemistry. © 2020 Societe Francaise de Chimie. All rights reserved.

Abstract The sodium-iodide symporter (NIS) mediates transport of iodide across the basolateral membrane of thyroid cells. NIS expression in thyroid cancer (TC) cells allows the use of radioactive iodine (RAI) as a diagnostic and therapeutic tool, being RAI therapy the systemic treatment of choice for metastatic disease. Still, a significant proportion of patients with advanced TC lose the ability to respond to RAI therapy and no effective alternative therapies are available. Defective NIS expression is the main reason for impaired iodide uptake in TC and NIS downregulation has been associated with several pathways linked to malignant transformation. NF-kappa B signaling is one of the pathways associated with TC. Interestingly, NIS expression can be negatively regulated by TNF-alpha, a bona fide activator of NF-kappa B with a central role in thyroid autoimmunity. This prompted us to clarify NF-kappa B's role in this process. We confirmed that TNF-alpha leads to downregulation of TSH-induced NIS expression in non-neoplastic thyroid follicular cell-derived models. Notably, a similar effect was observed when NF-kappa B activation was triggered independently of ligand-receptor specificity, using phorbol-myristate-acetate (PMA). TNF-alpha and PMA downregulation of NIS expression was reverted when NF-kappa B-dependent transcription was blocked, demonstrating the requirement for NF-kappa B activity. Additionally, TNF-alpha and PMA were shown to have a negative impact on TSH-induced iodide uptake, consistent with the observed transcriptional downregulation of NIS. Our data support the involvement of NF-kappa B-directed transcription in the modulation of NIS expression, where up-or down-regulation of NIS depends on the combined output to NF-kappa B of several converging pathways. A better understanding of the mechanisms underlying NIS expression in the context of normal thyroid physiology may guide the development of pharmacological strategies to increase the efficiency of iodide uptake. Such strategies would be extremely useful in improving the response to RAI therapy in refractory-TC.

Abstract An academic library created an online course in information literacy skills in 2007 for engineering students. This chapter reports the evaluation of the course's effectiveness in developing those skills. In the academic year 2015/2016, a case study with a mixed-methods approach was applied to 5th-year students (N=91) enrolled in a course unit for Master Dissertation's preparation in the informatics and computing engineering programme. Students showed high confidence in their information literacy skills. Online assignments' performance was good, but activities revealed quality issues. Performance in the course unit's assignments reveals a poor application of acquired skills. But satisfaction is high: students value independent learning and online access to resources and content. Despite evidence of some positive impact, the course lacks effectiveness due to issues in the course unit's assignments. Needed improvements include a better realignment with students' needs and a redesign with an instructional model to assure the promotion of students' success. © 2021 by IGI Global. All rights reserved.

Abstract In the present work, a detailed thermochemical, experimental and theoretical, study of benzocaine is presented. The enthalpy of formation in crystalline state at T = 298.15 K was obtained from combustion calorimetry experiments [ΔfHm°cr=-415.2±1.7kJ∙mol-1], within an oxygen atmosphere, using a static bomb calorimeter. The phase transition enthalpies (fusion, vaporization, and sublimation) were obtained by different techniques, namely differential scanning calorimetry, Calvet microcalorimetry, thermogravimetry, and the Knudsen effusion method. The results obtained by the different techniques are as follows: ΔcrlHm°298.15 K=21.4±0.1 kJ⋅mol−1; ΔlgHm°298.15 K=84.9±1.0 kJ⋅mol−1; ΔcrgHm°298.15 K=106.8±0.4 kJ⋅mol−1. From the experimental results, the enthalpy of formation of the aforesaid compound, in the gas phase, was calculated at T = 298.15 K as: ΔfHm°g=-308.4±1.8kJ∙mol-1. Theoretical enthalpies were computed using the Gaussian G4 composite method, atomization reactions, and the weighted Boltzmann average method. For the latter, the conformational diversity of the molecular structure of the compound was considered. Using the above data and using a similar approach, the theoretical entropy of benzocaine was computed as well. The experimental and theoretical values obtained were compared and an excellent accordance was found. Using the experimental and theoretical results, Gibbs energy of formation in crystalline and gaseous states of benzocaine, at T = 298.15 K were calculated as: ΔfGm°cr=-164.4kJ∙mol-1 and ΔfGm°g=-123.9kJ∙mol-1, respectively. Finally, the results obtained from the enthalpies of phase change are compared with those previously reported in the literature, in order to propose an exact value for these properties. © 2020 Elsevier Ltd

Abstract The energy involved in the structural switching of acyl and hydroxyl substituents in the title compounds was evaluated combining experimental and computational studies. Combustion calorimetry and Knudsen effusion techniques were used to determine the enthalpies of formation, in the crystalline state, and of sublimation, respectively. The gas-phase enthalpy of formation of both isomers was derived combining these two experimental data. Concerning the computational study, the G3(MP2)//B3LYP composite method was used to optimize and determine the energy of the isomers in the gaseous state. From a set of hypothetical reactions it has been possible to estimate the gas-phase enthalpy of formation of the title compounds. The good agreement between the experimental and computational gas-phase enthalpies of formation of the 1-acetyl-2-naphthol and 2-acetyl-1-naphthol isomers, provided the confidence for extending the computational study to the 2-acetyl-3-naphthol isomer. The structural rearrangement of the substituents in position 1 and 2 in the naphthalene ring and the energy of the intramolecular hydrogen bond are the factors responsible for the energetic differences exhibited by the isomers. The gas phase tautomeric keto <-> enol equilibria of theo-acetylnaphthol isomers were analyzed using the Boltzmann's distribution.

Abstract This article presents a promising application of Fourier transform-mid infrared (FT-MIR) spectroscopy with multivariate curve resolution - alternating least-squares (MCR-ALS) as an at-line process analytical technology (PAT) to enhancing the understanding and continuous control of a pharmaceutical manufacturing process. Its objective was to monitor the synthesis of pharmaceutical multicomponent crystals in solid-state, namely the mixture between lamivudine (active pharmaceutical ingredient-API) and saccharin (coformer) using liquid assisted grinding (LAG) in proportion of 1:1 in a ball mill. The continuous monitoring of synthesis procedure ensured product quality, revealing some of the events that can be detected during mechanochemical synthesis by FT-MIR spectroscopy with MCR-ALS. The concentration profiles retrieved by MCR-ALS allowed to identify the end of the salt synthesis. In fact, this is one of the advantages of real-time monitoring using FT-MIR spectroscopy and MCR-ALS, because it can be helpful not only to monitor and control a pharmaceutical manufacturing process, but also to optimize efficient use of energy, time and raw materials for lamivudine-saccharinate salt synthesis. Moreover, it allowed to understand that the antiretroviral lamivudine-saccharinate salt synthetized by LAG showed a fast reaction mechanism due to the presence of ethanol as catalyst. Differential scanning calorimetry (DSC) and X-ray powder diffraction (XRPD) techniques provided additional information needed to fully characterize pharmaceutical lamivudine-saccharinate salt synthetized by LAG technique.

Abstract Background: Half of human cancers harbour TP53 mutations that render p53 inactive as a tumor suppressor. As such, reactivation of mutant (mut)p53 through restoration of wild-type (wt)-like function represents one of the most promising therapeutic strategies in cancer treatment. Recently, we have reported the (S)-tryptophanolderived oxazoloisoindolinone SLMP53-1 as a new reactivator of wt and mutp53 R280K with in vitro and in vivo p53-dependent antitumor activity. The present work aimed a mechanistic elucidation of mutp53 reactivation by SLMP53-1. Methods and results: By cellular thermal shift assay (CETSA), it is shown that SLMP53-1 induces wt and mutp53 R280K thermal stabilization, which is indicative of intermolecular interactions with these proteins. Accordingly, in silico studies of wt and mutp53 R280K DNA-binding domain with SLMP53-1 unveiled that the compound binds at the interface of the p53 homodimer with the DNA minor groove. Additionally, using yeast and p53-null tumor cells ectopically expressing distinct highly prevalent mutp53, the ability of SLMP53-1 to reactivate multiple mutp53 is evidenced. Conclusions: SLMP53-1 is a p53-activating agent with the ability to directly target wt and a set of hotspot mutp53. General Significance: This work reinforces the encouraging application of SLMP53-1 in the personalized treatment of cancer patients harboring distinct p53 status.