Publications

Abstract Praziquantel (PZQ) is the drug of choice for oral treatment of schistosomiasis and other fluke infections that affect humans. Its low oral bioavailability demands the development of innovative strategies to overcome the first pass metabolism. In this article, solid lipid nanoparticles loaded with PZQ (PZQ-SLN) were prepared by a modified oil-in-water microemulsion method selecting stearic acid as lipid phase after solubility screening studies. The mean particle size (Z-Ave) and zeta potential (ZP) were 500 nm and -34.0 mV, respectively. Morphology and shape of PZQ-SLN were analysed by scanning electron microscopy revealing the presence of spherical particles with smooth surface. Differential scanning calorimetry suggested that SLN comprised a less ordered arrangement of crystals and the drug was molecularly dispersed in the lipid matrix. No supercooled melts were detected. The entrapment efficiency (EE) and loading capacity of PZQ, determined by high performance liquid chromatography, were 99.06 +/- 0.3 and 17.48 +/- 0.05, respectively. Effective incorporation of PZQ into the particles was confirmed by small angle X-ray scattering revealing the presence of a lipid lamellar structure. Stability parameters of PZQ-SLN stored at room temperature (25 degrees C) and at 4 degrees C were checked by analysing Z-Ave, ZP and the EE for a period of 60 days. Results showed a relatively long-term physical stability after storage at 4 degrees C, without drug expulsion.

Abstract Antimicrobial peptides (AMPS) take part in the immune system by mounting a first line of defense against pathogens. Recurrent structural and functional aspects are observed among peptides from different sources, particularly the net cationicity and amphipathicity. However, the membrane seems to be the key determinant of their action, either as the main target of the peptide action or by forming a barrier that must be crossed by peptides to target core metabolic pathways. More importantly, the specificity exhibited by antimicrobial peptides relies on the different lipid composition between pathogen and host cells, likely contributing to their spectrum of activity. Several mechanisms of action have been reported, which may involve membrane permeabilization through the formation of pores, membrane thinning or micellization in a detergent-like way. AMPs may also target intracellular components, such as DNA, enzymes and even organelles. More recently, these peptides have been shown to produce membrane perturbation by formation of specific lipid-peptide domains, lateral phase segregation of zwitterionic from anionic phospholipids and even the formation of non-lamellar lipid phases. To countermeasure their activity, some pathogens were successful in developing effective mechanisms of resistance to decrease their susceptibility to AMPs. The functional and integral knowledge of such interactions and the clarification of the complex interplay between molecular determinants of peptides, the pathogen versus host cells dichotomy and the specific microenvironment in which all these elements convene will contribute to an understanding of some elusive aspects of their action and to rationally design novel therapeutic agents to overcome the current antibiotic resistance issue.

Abstract Antioxidants are additives largely used in industry for delaying, retarding, or preventing the development of oxidative deterioration. Propyl gallate (E310) is a phenolic antioxidant extensively used in the food, cosmetics, and pharmaceutical industries. A series of lab experiments have been developed to teach students about the importance and significance of antioxidants in industry. In the first laboratory, the antioxidant propyl gallate is obtained and the structure identified. Students become acquainted with laboratory techniques such as extraction, crystallization, and thin-layer chromatography. In the second laboratory, spectroscopic data (IR, H-1 and C-13 NMR) is acquired and interpreted. Students become familiar with the basic concepts of organic compound identification. In the third laboratory, the antioxidant activity of the synthesized additive and gallic acid is evaluated by DPPH (2,2-diphenyl-1-picrythydrazyl) assay using trolox (6-hydroxy-2,5,7,8-tetramethylchroman-2-carboxylic acid) as standard. Concepts such as free radical chemistry, preparation of analytical samples, calibration methods, and UV-vis spectrophotometry, are reviewed. This series of experiments can also be used to explore the effect of substituents on radical stability because structurally related compounds were found to have qualitatively different antioxidant profiles.

Abstract The measurement of aryl-naphthyl rotational barriers, Delta G(double dagger), in various solvents for two substituted 1,8-diarylnaphthalenes by dynamic H-1 NMR showed that Delta G(double dagger) trends in aromatic systems can be fully rationalized only when considering the different types of aromatic interactions that can be established in the ground and transition states, namely, intramolecular interactions involving the aromatic rings and specific solvation interactions.

Abstract The chlorophenoxy herbicide MCPA(4-chloro-2-methylphenoxyacetic acid), widely used for the control of broad-leaf weeds primarily in cereal and grass seed crops, still remains one of the most often used herbicides in Portugal. As the formation of inclusion complexes with cyclodextrins can improve its solubility properties, the interaction between the herbicide MCPA and beta-cyclodextrin was investigated. The stability constants describing the extent of formation of the complexes have been determined by phase-solubility studies. Different analytical techniques [ultraviolet-visible spectroscopy (UV-Vis), differential scanning calorimetry (DSC), Fourier transform infrared spectroscopy (FTIR), proton nuclear magnetic resonance spectroscopy (H-1 NMR)] were employed for a thorough investigation of the structural characteristics of the obtained complexes, which exhibited distinct features and properties from both "guest" and "host" molecules. FTIR and H-1 NMR data obtained for the MCPA/beta-CD complexes gave information about the interaction between MCPA and the nonpolar cyclodextrin cavity. The dramatic change observed in band frequency and proton displacements of OCH2 group and H6 aromatic proton confirmed the inclusion of MCPA in beta-CD. The formation of an inclusion complex between MCPA and beta-CD increased the aqueous solubility of this herbicide which could be a particularly advantageous property for some specific applications, namely to improve commercial formulation and for environmental protection.

Abstract We report a study on the energetics and structural properties of naphthalene-based proton sponges and their corresponding protonated cations. In particular, we have determined the experimental standard enthalpies of formation in the gas phase at T = 298.15 K, Delta fH(m)(o) m (g), for the neutral and protonated DMAN [1,8-bis (dimethylamino)-naphthalene], (221.0 +/- 7.3) and (729.0 +/- 11.1) kJ.mol(-1), respectively. A reliable experimental estimation of enthalpy associated with "strain'' effect and hydrogen bond intramolecular (included within "enhanced basicity'', EB) contributions to the basicity of DMAN, were deduced from isodesmic reactions, -(29.1 +/- 4.6) and (87.1 +/- 11.9) kJ.mol(-1), respectively. The gas-phase basicities (GB) of naphthalene-based proton sponges are compared with the corresponding aqueous basicities (pKa), covering a range of 149 kJ.mol(-1) in GB and 11.5 in pKa. Density functional calculations at the M05-2X/6-311++G(d,p) level of theory were used to check the consistency of the experimental results and also to estimate the unavailable GB values of the considered species.

Abstract In this work, the interplay between structure and energetics in some representative phenylnaphthalenes is discussed from an experimental and theoretical perspective. For the compounds studied, the standard molar enthalpies, entropies and Gibbs energies of sublimation, at T = 298.15 K, were determined by the measurement of the vapor pressures as a function of T, using a Knudsen/quartz crystal effusion apparatus. The standard molar enthalpies of formation in the crystalline state were determined by static bomb combustion calorimetry. From these results, the standard molar enthalpies of formation in the gaseous phase were derived and, altogether with computational chemistry at the B3LYP/6-311++G(d,p) and MP2/cc-pVDZ levels of theory, used to deduce the relative molecular stabilities in various phenylnaphthalenes. X-ray crystallographic structures were obtained for some selected compounds in order to provide structural insights, and relate them to energetics. The thermodynamic quantities for sublimation suggest that molecular symmetry and torsional freedom are major factors affecting entropic differentiation in these molecules, and that cohesive forces are significantly influenced by molecular surface area. The global results obtained support the lack of significant conjugation between aromatic moieties in the alpha position of naphthalene but indicate the existence of significant electron delocalization when the aromatic groups are in the beta position. Evidence for the existence of a quasi T-shaped intramolecular aromatic interaction between the two outer phenyl rings in 1,8-di([1,1-biphenyl]4-yl)naphthalene was found, and the enthalpy of this interaction quantified on pure experimental grounds as -(11.9 +/- 4.8) kJ.mol(-1), in excellent agreement with the literature CCSD(T) theoretical results for the benzene dimer.