Publications

Abstract Adsorption of uranyl ions onto kaolinite, montmorillonite, humic acid and composite clay material (both clays and humic acid) was studied by measuring the system response to clay suspensions (pre-equilibrated with or without uranyl) and to perturbations of the solution chemistry. Adsorption behavior of selected materials under the frame of batch experiments was tested at high uranyl concentrations (6-1170 mu g/mL; 2.5 x 10(-2) to 4.9 mu M), whereas that under flow through continuous stirred reactor experiments was tested at low concentrations (1.00 x 10(-4) to 1.18 x 10(-4) M). Both experiments were developed at pH 4.5 and ionic strength 02 mM. The adsorption experiments follow a Langmuir isotherm model with a good correlation coefficient (R-2 > 0.97). The calculated amount of adsorbed and desorbed uranyl was carried out by numeric integration of the experimental data, whereas the desorption rates were determined from the breakthrough curve experiments. Kaolinite with highly disordered structure adsorbed less uranyl (3.86 x 10(-6) mol/g) than well-ordered kaolinite (1.76 x 10(-5) mol/g). Higher amount of uranyl was adsorbed by montmorillonite (3.60 x 10(-5) mol/g) and only half of adsorbed amount was desorbed (1.85 x 10(-5) mol/g). The molecular interactions between kaolinite, montmorillonite, humic acid, composite material and saturated uranyl ion solutions were studied by molecular fluorescence, infrared and X-ray photoelectron spectroscopy. The Stem-Volmer constant obtained for montmorillonite (2.6 x 10(3) M-1) is higher than for kaolinite (0.3 x 10(3) M-1). Molecular vibrations of Si-O stretching and Al-OH bending related to hydroxylated groups ( SiOH or AlOH) of kaolinite and montmorillonite show structural changes when uranyl ions are adsorbed. X-ray photoelectron spectroscopy shows that the U 4f(7/2) core level signals occur at 380.5 eV in either kaolinite or montmorillonite that resulted from the interaction of aluminol surface sites with the (UO2)(3)(OH)(5)(+).

Abstract This is the first report of a study employing a computational approach to study the binding of (D/L)-luciferyl-adenlyates and dehydroluciferyl-adenylate to firefly luciferase. A semi-empirical/molecular mechanics methodology was used to study the interaction between these ligands and active site molecules. All adenylates are complexed with the enzyme, mostly due to electrostatic interactions with cationic residues. Dehydroluciferyl-adenylate is expected to be a competitive inhibitor of luciferyl-adenylate, as their binding mechanism and affinity to luciferase are very similar. Both luciferyl-adenylates adopt the L-orientation in the active site of luciferase.

Abstract Firefly luciferase is the most important and studied bioluminescence system. Due to very interesting characteristics, this system has gained numerous biomedical, pharmaceutical and bioanalytical applications, among others. In order to improve the use of this system, various researchers have tried to understand experimentally the colour of bioluminescence, and to create ways of tuning the colour emitted. The objective of this manuscript is to review the experimental studies of firefly luciferin and oxyluciferin, and related analogues, fluorescence and bioluminescence.

Abstract Parkinson's disease (PD) is one of the most common neurodegenerative disorders. The role of monoamine oxidase (MAO) inhibitors has expanded in the PD treatment. The present review will summarize the current structure-activity relationship information available on MAOs inhibitors of unrelated families of compounds of oxygen heterocyclic type based on coumarin, chromone and chalcone scaffolds. As the current hitting-one-target therapeutic strategy has been proved to be quite inefficient in PD, this review will also discuss about the development of multi-target drugs, in which MAO inhibition plays a counter-part, as a novel and promising treatment approach for PD.

Abstract Adenosine receptors (ARs) are widespread on virtually every human organ/tissue, and have long been considered promising therapeutic targets in a wide range of conditions, ranging from cerebral diseases to cancer, including inflammatory disorders. The knowledge acquired up to date in relation to ARs, in particular regarding the molecular biology of the A(3) AR has provided a solid basis that led to the proposal of this receptor as a novel therapeutic target enabling the rational design and development of potent and selective A(3) AR ligands. This review attempts to summarize the most recent developments in the A(3) research field, focusing in particular on Quantitative Structure-Activity Relationships (QSAR) based studies that supported so far the design of new, potent and selective human A(3) AR antagonists. In addition, a classical QSAR modeling study carried out on two series of pyrazolo-triazolopyrimidine derivatives is presented as a case study. Specifically, a systematic evaluation of linear and non-linear models along with a variety of structure representations and feature selection tools is reported. The combination of these techniques (neural networks to capture non-linear relationships in the data and feature selection to prevent over-fitting) was found to produce QSAR models with good overall accuracy and robustness, as well as predictivity on external data. Moreover, the study indicated that the antagonist activity of these derivatives is largely explained by electrostatic, steric and hydrogen-bonding factors, highlighting the role of the size, shape and type of inhibitor in forming effective blocking of the A(3) AR subtype. The developed QSAR models could then be usefully employed to design new compounds selectively active towards the A(3) adenosine receptor.

Abstract beta-Cyclodextrin was modified with 11-[(ethoxycarbonyl)thio]undecanoic acid and used as a capping agent, together with mercaptosuccinic acid, to prepare water-stable CdTe quantum dots. The water soluble quantum dot obtained displays fluorescence with a maximum emission at 425 nm (under excitation at 300 nm) with lifetimes of 0.53, 4.8, 181, and 44.1 ns, respectively. The S-beta CD-MSA-CdTe can act as a nanoprobe that is due to the affinity of the cyclodextrin moiety for selected substances such as acetylsalicylic acid (ASA) and its metabolites as foreign species. The fluorescence of the S-beta CD-MSA-CdTe is enhanced on addition of ASA. Linear calibration plots are observed with ASA in concentrations between 0 and 1 mg/l, with a limit of detection at 8.5 x 10(-9) mol/1 (1.5 ng/ml) and a precision as relative standard deviation of 1% (0.05 mg/l). The interference effect of certain compounds as ascorbic acid and its main metabolites such as salicylic, gentisic and salicyluric acid upon the obtained procedure was studied.

Abstract With the ultimate purpose of finding out the structural features that are relevant for MAO inhibitory activity and selectivity towards MAO-B isoform, a series of compounds encompassing a beta-nitrostyrene moiety was designed and the in vitro inhibitory activity was evaluated. In the present work, we report the synthesis and the pharmacological evaluation of a series of functionalized derivatives of beta-methyl-beta-nitrostyrene with distinct substitution patterns in the phenyl ring, namely hydroxyl, methoxy, benzyloxy and methylenedioxy. All the studied compounds were substituted in meta and para positions of the phenyl ring related to the nitrovinyl side chain. The synthesized compounds were evaluated towards both human MAO isoforms, displaying some of them activities in the low micromolar range. Particularly compound 6 (a methylenedioxy derivative) exhibits high potency and selectivity towards MAO-B.

Abstract Four different generation of thiol-DAB dendrimers were synthesized, S-DAB-G(x) (x = 1, 2, 3 and 5), and coupled with CdSe quantum dots, to obtain fluorescent nanocomposites as metal ions sensing. Cd(II) and Pb(II) showed the higher enhancement and quenching effects respectively towards the fluorescence of S-DAB-G(5)-CdSe nanocomposite. The fluorescence enhancement provoked by Cd(II) can be linearized using a Henderson-Hasselbalch type equation and the quenching provoked by Pb(II) can be linearized by a Stern-Volmer equation. The sensor responds to Cd(II) ion in the 0.05-0.7 mu M concentration range and to Pb(II) ion in the 0.01-0.15 mM concentration range with a LOD of 0.06 mM. The sensor has selectivity limitations but its dendrimer configuration has analytical advantages.

Abstract A fluorescence chemical sensor for C-reactive protein (CRP) was developed based on the selective interaction with CdSe and ZnSe quantum dots (QDs) coated with O-phosphorylethanolamine (PEA). Synthesis procedure and analytical parameters such as pH and ionic strength were studied. The decrease in the fluorescence emission intensity was explained due to the specific interaction of the QDs-PEA with CRP, and a correlation was observed between the quenching of the fluorescence and the concentration of CRP. The accuracy of the proposed method was 0.37% as RSD. The proposed method was applied to screen serum samples, and showed to be sensible at the C-reactive protein concentrations of risks levels.

Abstract A nanocomposite obtained by a thiol DAB-dendrimer (generation 5), coated with fluorescent ZnSe quantum dots, was successfully synthesized for the selective recognition of C-reactive protein. The procedure presented was carried out by a novel, cheap and non-toxic bottom up synthesis. The nanocomposite showed an excitation at 180 nm, with two emission bands at 411 and 465 nm, with a full-width at half-maximum of 336 nm. The Stokes shift was influenced by the presence of coating molecules and the intensity was dependent on pH due to the presence of a charge transfer process. The transmission electron microscopy images demonstrated that the spherical nanoparticles obtained displayed a regular shape of 30 nm size. The fluorescence intensity was markedly quenched by the presence of C-reactive protein, with a dynamic Stern-Volmer constant of 0.036 M-1. The quenching profile shows that about 51% of the ZnSe QDs are located in the external layer of the thiol dendrimer accessible to the quencher. The precision of the method obtained as relative standard deviation was 3.76% (4 mg L-1, n=3). This water soluble fluorescent nanocomposite showed a set of favorable properties to be used as a sensor for the C-reactive protein in serum samples, at concentrations of risk levels.