Publications

Abstract This work presents the vapor pressure at several temperatures for the 1,3-dialkylimidazolium bis(trifluoromethylsulfonyl)imide series, [C(N/2)C(N/2)im][NTf2] (N = 14, 16, 18, and 20), measured by a Knudsen effusion method combined with a quartz crystal microbalance. The thermodynamic properties of vaporization of the ionic liquids under study are analysed together with the results obtained previously for the shorter alkyl chain length [C(N/)2C(N/)2im][NTf2] (N = 2, 4, 6, 8, 10, and 12), in order to evaluate the effect of the alkyl side chains of the cation and to get additional insights concerning the nanostructuration of ionic liquids. The symmetry effect is explored, based on the comparison with the asymmetric imidazolium based ionic liquids, [C(N-1)C(1)im][NTf2]. A trend shift on the thermodynamic properties of vaporization along the alkyl side chains of the extended symmetric ionic liquids, around [C(6)C(6)im][NTf2], was detected. An intensification of the odd-even effect was observed starting from [C(6)C(6)im][NTf2], with higher enthalpies and entropies of vaporization for the odd numbered ionic liquids, [C(7)C(7)im][NTf2] and [C(9)C(9)im][NTf2]. Similar, but less pronounced, odd-even effect was found for the symmetric ionic liquids with lower alkyl side chains length, [C(N/2)C(N/2)im][NTf2] (with N = 4, 6, 8, 10, and 12). This effect is related with the predominant orientation of the terminal methyl group of the alkyl chain to the imidazolium ring and their influence in the cation-anion interaction. The same Critical Alkyl length at the hexyl, (C6C1 and C6C6) was found for both asymmetric and symmetric series indicating that the nanostructuration of the ionic liquids is related with alkyl chain length. (C) 2014 AIP Publishing LLC.

Abstract This work reports an experimental and computational thermochemical study for benzothiazole and two of its methyl benzothiazole derivatives, 2-methylbenzothiazole and 2,5-dimethylbenzothiazole. Values of the standard (p(o) = 0.1 MPa) molar energy of combustion of the three compounds were measured by rotating bomb combustion calorimetry. The standard molar enthalpy of the corresponding transitions from condensed to gaseous phases, at T = 298.15 K, was obtained from high temperature Calvet microcalorimetry measurements. The experimental results enable the calculation of the standard molar enthalpy of formation in the gaseous state, at T = 298.15 K, for the afore-mentioned compounds, the results being discussed in terms of structural and energetic contributions. The gas-phase enthalpies of formation were computationally estimated from high-level ab initio molecular orbital calculations at the G3//B3LYP level of theory. The computed values compare very well with the experimental results obtained in this work and show that, in terms of enthalpy, the methyl substituents lead to an increase on the stability of the compounds, in a similar way to that already described for the corresponded benzoxazole derivatives. Furthermore, this composite approach was also used to obtain information about the gas-phase basicity, proton and electron affinities and adiabatic ionization enthalpies.

Abstract The standard (p degrees = 0.1 MPa) molar enthalpies of formation, at T = 298.15 K, in the gaseous phase, for two nitrobenzofurazan derivatives, 4-N,N-dimethylamino-7-nitrobenzofurazan (DMANBF) and 4-N,N-diethylamino-7-nitrobenzofurazan (DEANBF), were derived from their enthalpies of combustion and sublimation, obtained by static bomb calorimetry and by the Knudsen effusion technique, respectively. The results are compared with the corresponding data calculated by the G3(MP2)//B3LYP approach. Computationally, the molecular structures of both compounds were established and the geometrical parameters were determined at the B3LYP/6-31G(d) level of theory.

Abstract This work reports an experimental and computational thermochemical study for 2-benzothiazolinone. The standard (p degrees = 0.1 MPa) molar energy of combustion of this compound was measured by rotating bomb combustion calorimetry. The standard molar enthalpy of the corresponding transition from crystalline to gaseous phases, at T = 298.15 K, was obtained from high temperature Calvet microcalorimetry measurements. The experimental results enable the calculation of the standard molar enthalpy of formation of the compound, in the gaseous state, at T = 298.15 K. The gas-phase enthalpies of formation of the title compounds, 2-benzothiazolinone and its enol form 2-hydroxybenzothiazole, were estimated computationally from high-level oh initio molecular orbital calculations at the G3(MP2)//B3LYP level of theory. The computed value for the keto form compares very well with the experimental result obtained in this work. The hydroxy <-> oxo tautomerism of the title compounds was explored in this work as it may be relevant to their ability to occur as different polymorphic forms.

Abstract Zinc oxide is widely used in the manufacture of a vast number of consumer goods and industrial applications. The employ of nano and sub-micrometer zinc oxide materials has recently been introduced as a more economic and more effective alternative to bulk zinc oxide. Furthermore zinc oxide is being used as antibacterial material since metal oxides are recognized as possessing antibacterial properties and are regarded as safe materials to human beings and animals. The present work aims to present our study on the antibacterial properties of zinc oxide particles prepared by a polyol thermal method. Spherical submicrometer ZnO particles were prepared and their antibacterial properties were tested in aqueous suspensions of E. coli bacteria. For ZnO concentrations higher than 50 ppm an inhibition of the growth rate of bacteria higher than 95 % is achieved.

Abstract Solid lipid nanoparticles (SLN) are colloidal drug and/or gene carriers developed from solid lipids and surfactants that are considered safe. Cationic SLN, usually used for formulating poorly water-soluble drugs and for gene delivery purposes, as positively charged particles may attach to cellular surfaces and be internalized more easily than negatively charged SLN, but they can also cause damage. The main aim of this work was to test a set of cationic SLN and investigate its influence on the amount of reactive oxygen species (ROS), on antioxidant enzymes activities and on possible oxidative damage to membrane lipids in HepG2 cells. The Dichlorofluorescein assay revealed great increase in ROS presence after cell exposure to SLN. While the exposure to SLN increased the activities of superoxide dismutase and glutathione peroxidase it decreased glutathione reductase activity. Although no significant increase in thiobarbituric reactive species was found, a decrease in sulfhydryl groups was detected. These results indicate that cationic SLN caused oxidative stress in HepG2 cells, but under reported exposure conditions HepG2 cells could attenuate the stress and thus the damage to cellular components was minimal.

Abstract The enthalpies of solution of alcohols were determined by calorimetry in HEPES and (HEPES + trehalose) at 298.15 K. The used methodology and experiment's design allowed us to extract from a single titration experiment the enthalpy of solution (Delta H-sol(m)), the limiting solubility of the alcohol in each aqueous media, and an estimation of the enthalpy of solution of water in the alcohol phase. From these values the changes in Gibbs energy (Delta(sol)G(m)) and in entropy (Delta S-sol(m)) of solution were derived. A decrease in solubility for 1-butanol and 1-pentanol in the crowded media (HEPES + trehalose) was observed which is driven by a significant decrease in the favorable enthalpy of solution. The partial molar heat capacity, C-p,2(infinity) in each media was determined in our heat capacity drop calorimeter, also at 298.15 K. A significant decrease of the partial molar heat capacity was observed for both alcohols in (HEPES + trehalose), which together with the obtained decrease in favorable Delta H-sol(m), is consistent with a decrease in hydrophobic solvation, as a result of a decrease in free solvent availability induced by the trehalose. Finally, we tentatively predict that in the aqueous media of the crowded solutions that characterize cells and biological fluids, solutes with low aqueous solubility will be more soluble, whereas the solubility of highly polar solutes will be reduced.

Abstract The development of new drugs always was time consuming and costly. With the development in experimental methods was possible to scan small-compounds libraries in order to find potentially suitable molecules. Nevertheless, these methods are able to so with a very low rate. Protein kinases are a class of enzymes involved in the great majority of cellular process. Due to its presence in many signal pathways, cell cycle and gene expression control mechanisms, this class is one of the major targets for pharmaceutical industries today. Aiming the reduction of time and costs in drug development computational tools started to be used, and commonly called Computer aided drug design (CADD). These methods can be separated in two different types of approaches, structure based (SBDD) and ligand based (LBDD). In order to use structure based methods, information about the 3D structure of the target is needed, normally obtained through x-ray crystallography or NMR. Ligand based methods are preferred when this information is not available. The focus of the present chapter is the structure based methods used in the computer drug discovery and design process targeting kinases. Starting with the visual and energetic analysis of the binding site, it is obtained enough information for the creation of a Pharmacophore model and the application of Virtual Screening process. The results of the screening can then be analysed through Molecular Docking process followed by Molecular Dynamics in order to better simulate the real binding conditions. The obtained complexes can be analysed using energy calculations, in order to better understand the binding process. Within the described procedures, computational tools originate a great amount of useful information since hit discovery from lead optimization. The data obtained can save time and reduce costs in the process of drug design and discovery in a large scale.

Abstract The raising level of awareness regarding the harmful effects of solar radiation has resulted in an increase in the production and use of sunscreens. These commercial products contain ultraviolet (UV) filters that absorb, reflect or scatter UV radiation (290-320 nm for UVB and 320-400 nm for UVA) therefore preventing sunburn, photo-aging and ultimately skin diseases such as skin cancer. A high screening efficiency can only be guaranteed if a UV filter has a high photo-stability. However, UV filters are known to undergo degradation upon exposure to sunlight and chemical substances used in water disinfection such as chlorine, leading to the formation of undesirable byproducts with properties different from the parent compounds. This chapter presents a comprehensive review on the computational studies performed so far on the structural, electronic, energetic and UV absorption properties of some of the most widely used UV-filters and their degradation products (UVFDP). Ab initio and density functional theory (DFT) methods have been used to obtain the molecular structure, energetics and other molecular properties of UVF-DP. UV-Vis absorption spectra and excited state properties have been calculated using the time dependent density functional theory (TD-DFT). The influence of different solvents in these properties has been studied using solution models. Transformation and degradation mechanisms have been established with the aid of computational methods and results indicate that these can be employed to assess the environmental fate of UV-filters.

Abstract In the present study we have developed lipid nanoparticle (LN) dispersions based on a multiple emulsion technique for encapsulation of hydrophilic drugs or/and proteins by a full factorial design. In order to increase ocular retention time and mucoadhesion by electrostatic attraction, a cationic lipid, namely cetyltrimethylammonium bromide (CTAB), was added in the lipid matrix of the optimal LN dispersion obtained from the factorial design. There are a limited number of studies reporting the ideal concentration of cationic agents in LN for drug delivery. This paper suggests that the choice of the concentration of a cationic agent is critical when formulating a safe and stable LN. CTAB was included in the lipid matrix of LN, testing four different concentrations (0.25%, 0.5%, 0.75%, or 1.0%wt) and how composition affects LN behavior regarding physical and chemical parameters, lipid crystallization and polymorphism, and stability of dispersion during storage. In order to develop a safe and compatible system for ocular delivery, CTAB-LN dispersions were exposed to Human retinoblastoma cell line Y-79. The toxicity testing of the CTAB-LN dispersions was a fundamental tool to find the best CTAB concentration for development of these cationic LN, which was found to be 0.5 wt% of CTAB.