Publications

Abstract A fluorescence derivatization method for the quantification of the anthelmintic drug niclosamide in organized media (methyl-beta-cyclodextrin) is described. The derivatization reaction is based on a 3 h reduction reaction of the nitro group in niclosamide to an amino group by hydrogenation catalyzed by Pd/C in methanol:ethyl acetate (1:3). The aminoniclosamide exhibits a maximum of fluorescence at 431 nm (excitation at 280 nm) that is markedly enhanced when methyl-beta-cyclodextrin is present. The methodology was assessed by the analysis of pure and dosage forms. The method showed a linear range between 0 and 2200 mu g L-1 with a limit of detection of 45.7 nIe and a precision (relative standard deviation) of 4.1% in niclosamide. The effect of various interferents, such as niclosamide, fructose and 2-cyano-6-metoxybenzothiazole, in several tolerance ratios, was investigated respected to aminoniclosamide.

Abstract The present work reports an experimental study on the energetics of 2,1,3-benzothiadiazole and a computational study on its structure, energetics and aromaticity. In the experimental part the standard (p(o) = 0.1 MPa) massic energy of combustion, at T = 298.15 K, was measured by rotating bomb combustion calorimetry, in oxygen, and allowed the calculation of the respective standard molar enthalpy of formation, in the crystalline phase, at T = 298.15 K. The standard molar enthalpy of sublimation, at T = 298.15 K, was measured by high-temperature Calvet microcalorimetry. From the combination of data obtained by both techniques we were able to calculate the respective standard molar enthalpy of formation, in the gas phase, at T = 298.15 K: (276.6 +/- 2.5) kJ . mol (1). This thermochemical parameter was compared with estimates obtained from high level ab initio quantum chemical calculations using the G3(MP2)//B3LYP composite method and various appropriately chosen reactions. The molecular structure of 2,1,3-benzothiadiazole was obtained from DFT calculations with the B3LYP density functional and various basis sets: 6-31G(d), 6-311(d, p), 6-311+G(3df, 2p), aug-ccpVTZ and aug-ccpVQZ and its aromaticity and that of some related molecules were evaluated by analysis of nucleus independent chemical shifts (NICS) values.

Abstract Firefly luciferase exhibits a multicolor bioluminescence, which is caused by the modulation of the emission of oxyluciferin by intermolecular interactions. One of the objectives of the present paper was analyze the possible effect of the charge density of the emitter in the color tuning. Theoretical calculations on oxyluciferin, and its respective moieties, demonstrated that no correlation between charge density and light emission can be found once solvent effects are considered. Further computational calculations demonstrate that intermolecular interactions modulate the emission by affecting the geometry of oxyluciferin, which controls the energy gap between the excited and ground state. Direct intermolecular interactions and polarity also affect the color of emission of oxyluciferin, by the same mechanism. Also, the effect of charge density modulation of Keto-(-1). A novel emitter, 5-hydroxyoxyluciferin, was considered and demonstrated to be more red-shifted that oxyluciferin.

Abstract This paper reports an experimental and computational study on the energetics of 1,2,3-benzotriazin-4(3H)-one. The standard (p degrees = 0.1 MPa) molar enthalpy of formation of solid 1,2,3-benzotriazin-4(3H)-one, at T = 298.15 K, was derived from its standard massic energy of combustion measured by static bomb combustion calorimetry in oxygen. The Calvet high-temperature vacuum sublimation technique was used to measure the respective standard molar enthalpy of sublimation at T = 298.15 K From these two experimentally determined thermodynamic parameters, we have calculated the standard molar enthalpy of formation of 1,2,3-benzotriazin-4(3H)-one in the gas phase at T = 298.15 K, (200.9 +/- 3.8) kJ . mol(-1). Interrelations between structure and energy for 1,2,3-benzotriazin-4(3H)-one, the tautomer 1,2,3-benzotriazin-4(1H)-one, and the enol tautomer 1,2,3-benzotriazin-4-ol were discussed based on density functional theory (DFT) calculations with the B3LYP hybrid functional and the 6-311++G(d,p) basis set. The gas-phase enthalpy of formation of 1,2,3-benzotriazin-4(3H)-one was estimated from quantum chemical calculations using the G3(MP2)//B3LYP composite method. Nucleus-independent chemical shifts (NICS) were also calculated with the purpose of analyzing the aromaticity of the benzenic and heterocyclic rings of the title molecule and others related tautomerically to it.

Abstract Electroactive polymer films based on [Ni(salen)]-type complexes were fabricated and their electronic properties characterized using in situ UV-visible spectroelectrochemistry. The extent of pi electronic delocalisation and electronic asymmetry were manipulated by introduction of different conjugated imine bridges. Measured electronic spectra were interpreted in terms of polaronic states in the band gap and metal-oxidized ligand charge transfer bands. Density functional theory (DFT) calculations for the monomers showed that the HOMO orbital (which governs oxidation potential) is ligand-dominated, and that substituents with greater electronic delocalisation in the diimine bridge decrease the HOMO-LUMO energy gap. Replacement of methyl by methoxyl substituents in the aldehyde moiety increases the calculated dipole moment. Substitution-driven variations in E(HOMO)-E(LUMO) for the monomers were reflected in the corresponding polymer band gaps, demonstrating that monomer electronic properties can be used predictively in the manipulation of polymer electronic properties. An important strategic aspect is the correlation of OFF predictions with the observed electronic properties of monomeric and polymeric materials; the extent to which such modelling can be used to optimise synthetic effort is discussed.

Abstract Vapor pressures of some azides have been determined by the transpiration method. The molar enthalpies of vaporization Delta(g)(I)H(m) of these compounds were derived from the temperature dependencies of vapor pressures. The measured data sets were successfully checked for internal consistency by comparison with vaporization enthalpies of similarly structured compounds.

Abstract Potent and selective ligands with a nucleoside skeleton are generally thought as agonists of the human A(3) adenosine receptor (AR), however, some of them can also act as full antagonists. This work reports a Quantitative Structure-Activity Relationship (QSAR) study for predicting the binding affinity of such type of compounds towards the A(3) AR. Several different theoretical molecular descriptors, calculated only on the basis of knowledge of the molecular structure and an efficient variable selection procedure, such as forward stepwise regression, led to models with satisfactory accuracy and predictive ability. But the best-final QSAR model is based on the Molecule Representation of Structures based on Electron diffraction (3D-MoRSE) descriptors capturing a reasonable interpretation. This QSAR model is able to explain more than 85% of the variance in the experimental affinity and manifests good predictive ability as indicated by the higher Q(2)s of cross-and external-validations. The model obtained in this study may provide guidance for future design of new potent and selective human A(3) AR full antagonists with a nucleoside skeleton.

Abstract This paper presents the main results of RP-HPLC-MS and microscale NMR analysis performed on Accompanying similar to Luciferin (AsLn(x)), compounds present in extracts of the bioluminescent earthworm Fridericia heliota that display similarities with Fridericia's luciferin, the substrate of the bioluminescent reaction. Three isomers of AsLn were discovered, AsLn(1), AsLn(2) and AsLn(3), all of which present a molecular weight of 529 Da. Their UV-Vis absorption spectra show maxima at 235 nm for AsLn(1), 238 and 295 nm for AsLn(2) and 241 and 295 nm for AsLn(3). MSn fragmentation patterns suggest the existence of carboxylic acid and hydroxyl moieties, and possibly chemical groups found in other luciferins like pterin or benzothiazole. The major isomer, AsLn(2), presents an aromatic ring and alkene and alkyl moieties. These luciferin-like compounds can be used as models that could give further insights into the structure of this newly discovered luciferin.

Abstract Methamphetamine (METH) is a powerful stimulant drug of abuse that has steadily gained popularity worldwide. It is known that METH is highly neurotoxic and causes irreversible damage of brain cells leading to neurological and psychiatric abnormalities. Recent studies suggested that METH-induced neurotoxicity might also result from its ability to compromise blood-brain barrier (BBB) function. Due to the crucial role of BBB in the maintenance of brain homeostasis and protection against toxic molecules and pathogenic organisms, its dysfunction could have severe consequences. In this study, we investigated the effect of an acute high dose of METH (30 mg/kg) on BBB permeability after different time points and in different brain regions. For that, young adult mice were sacrificed 1 h, 24 h or 72 h post-METH administration. METH increased BBB permeability, but this effect was detected only at 24 h after administration, being therefore a transitory effect. Interestingly, we also found that the hippocampus was the most susceptible brain region to METH, comparing to frontal cortex and striatum. Moreover, in an attempt to identify the key players in METH-induced BBB dysfunction we further investigated potential alterations in tight junction (TJ) proteins and matrix metalloproteinase-9 (MMP-9). METH was able to decrease the protein levels of zonula occludens (ZO)-1, claudin-5 and occludin in the hippocampus 24 h post-injection, and increased the activity and immunoreactivity of MMP-9. The pre-treatment with BB-94 (30 mg/kg), a matrix metalloproteinase inhibitor, prevented the METH-induced increase in MMP-9 immunoreactivity in the hippocampus. Overall, the present data demonstrate that METH transiently increases the BBB permeability in the hippocampus, which can be explained by alterations on TJ proteins and MMP-9.

Abstract A convenient, new, and effective protocol for a rapid synthesis of different substituted 3-arylcoumarins is reported. The developed synthetic route involves Pd-catalyzed cross-coupling reaction, using a catalytic complex Pd-salen. Under these conditions, a series of different substituted boronic acids have been successfully reacted with a coumarin halide to afford the coupling products in good yields.