Publications

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.

Abstract The use of deep eutectic solvents (DES) for metal electrodeposition has become an area of interest in the recent years however the use of additives on the electrodeposition from deep eutectic solvents is still an unexplored area. In this study we describe the influence of the tartrate ion on the deposition mechanism of zinc and on the resultant morphology of the deposits. Electrochemical techniques were used to characterize the deposition process and scanning electron microscopy was used to study the deposit morphology. It is shown that the presence of potassium hydrogen tartrate in ethaline does not alter the generic voltammetric profile of zinc in solution but in contrast the presence of tartaric acid cause major modifications. From the analysis of the chronoamperometric transients a 3D progressive nucleation mechanism is proposed for the deposition of zinc in absence and in the presence of potassium hydrogen tartrate. In the presence of tartaric acid a 2D progressive nucleation mechanism is proposed for the initial part of the deposition then changing to a 3D progressive mechanism. The SEM images reveal that both additives change the morphological characteristics of the deposits. However the use of tartaric acid introduces a more dramatic change.

Abstract Bisnaphthalimidopropyl (BNIP) derivatives have recently been shown to have potential as antileishmanial agents. However, these compounds have some drawbacks, including their low aqueous solubility and some toxic effects. In this study, we designed a drug delivery system for enhanced delivery of BNIP derivative compounds whilst reducing adverse toxic effects, and hence increasing their biological efficacy. A coated drug delivery system based on polymeric nanoparticles of pegylated poly(lactic acid) (PLA), a biodegradable polymer, was successfully achieved. The pegylated PLA nanoformulations loaded with BNIP derivatives were evaluated in an in vitro model of intracellular amastigotes in murine J774 and human THP-1 cells for visceral leishmaniasis using luciferase-expressing Leishmania infantum parasites. Pegylation of PLA nanoparticles significantly reduced the capacity of empty nanoparticles in inhibiting intracellular parasite growth. The BNIP derivatives BNIPDadec and BNIPDaoct exhibited EC50 values (concentration of compound necessary to decrease cell viability to 50% of the untreated control) of ca. 4.5 mu M for THP-1 and J774 cells and ca. 9.0 mu M for mouse bone marrow-derived macrophages. Nanoparticle encapsulation of the BNIP derivative compounds decreased their toxicity towards macrophages by >= 10-fold as evaluated by the MTT assay. The antileishmanial activity of free BNIPDadec was 1.02 +/- 0.41 mu M and 0.73 +/- 0.06 mu M for THP-1 and J774 macrophages, respectively. Pegylation of PLA nanoparticles loaded with BNIPDadec resulted in EC50 values of 1.43 +/- 0.63 mu M and 1.79 +/- 0.77 mu M for THP-1 and J774 macrophages, respectively. A similar trend was observed for free BNIPDaoct and pegylated BNIPDaoct PLA nanoparticles (2.43 perpendicular to 0.19 mu M and 1.23 perpendicular to 0.40 mu M for THP-1 macrophages and 1.36 +/- 0.17 mu M and 1.52 +/- 0.57 mu M for J774 macrophages). The nanoformulations were more efficient in reducing parasitic growth inside human macrophages than in murine cells, suggesting host cell-dependent metabolism.

Abstract Ultraviolet (UV) filters are vital constituents of sunscreens and other personal care products since they absorb, reflect and/or scatter UV radiation, therefore protecting us from the sun's deleterious UV radiation and its effects. However, they suffer degradation, mainly through exposure towards sunlight and from reactions with disinfectant products such as chlorine. On the basis of their increasing production and use, UV filters and their degradation products have already been detected in the aquatic environment, especially in bathing waters. This paper presents a comprehensive review on the work done so far as to identify and determine the by-products of UV filter photodegradation in aqueous solutions and those subsequent to disinfection-induced degradation in chlorinated aqueous solutions, namely swimming pools.

Abstract In this work, the interaction between ethyl(hydroxyethyl) cellulose (EHEC) and three dimeric lysine-based surfactants of distinct chain length (C-6, C-8 and C-10) have been assessed and the system was evaluated in terms of its temperature-dependent gelling capacity. The viscosity profile depends on the specific surfactant, its concentration and temperature. The observed profiles reflected polymer-polymer associations at elevated temperatures and polymer-surfactant interactions, implying the formation of micellartype associations. The systems induce gelation at higher temperatures. Longer chain-length surfactants induce gelation at lower concentrations due to their stronger tendency to selfassemble. The thermo-responsive gels showed gel strength generally lower than 20 Pa.s(n) and a fractal dimension of 2.3-2.4, respectively, indicating the formation of soft gels comprising a tight and homogeneous network. The weakest gel was produced in the presence of the C-6 surfactant. 2D Small-Angle Light Scattering patterns showed a pronounced effect of temperature in terms of the evolution of large hydrophobic clusters, an event precluded when high concentrations of the longer chain surfactants were used.

Abstract We apply a new methodology in the force field generation (Phys. Chem. Chem. Phys. 2011, 13, 7910) to study binary mixtures of five imidazolium-based room-temperature ionic liquids (RTILs) with acetonitrile (ACN). Each RTIL is composed of tetrafluoroborate (BF4) anion and dialkylimidazolium (MMIM) cations. The first alkyl group of MIM is methyl, and the other group is ethyl (EMIM), butyl (BMIM), hexyl (HMIM), octyl (OMIM), and decyl (DMIM). Upon addition of ACN, the ionic conductivity of RTILs increases by more than 50 times. It significantly exceeds an impact of most known solvents. Unexpectedly, long-tailed imidazolium cations demonstrate the sharpest conductivity boost. This finding motivates us to revisit an application of RTIL/ACN binary systems as advanced electrolyte solutions. The conductivity correlates with a composition of ion aggregates simplifying its predictability. Addition of ACN exponentially increases diffusion and decreases viscosity of the RTIL/ACN mixtures. Large amounts of ACN stabilize ion pairs, although they ruin greater ion aggregates.

Abstract In this paper, we apply novel intrinsic analysis methods, coupled with bivariate orientation analysis, to obtain a detailed picture of the molecular-level structure of ionic liquid surfaces. We observe pronounced layering at the interface, alternating non-polar with ionic regions. The outermost regions of the surface are populated by alkyl chains, which are followed by a dense and tightly packed layer formed of oppositely charged ionic moieties. We then systematically change the cation chain length, the anion size, the temperature and the molecular model, to examine the effect of each of these parameters on the interfacial structure. Increasing the cation chain length promotes orientations in which the chain is pointing into the vapor, thus increasing the coverage of the surface with alkyl groups. Larger anions promote a disruption of the dense ionic layer, increasing the orientational freedom of cations and increasing the amount of free space. The temperature had a relatively small effect on the surface structure, while the effect of the choice of molecular model was clearly significant, particularly on the orientational preferences at the interface. Our study demonstrates the usefulness of molecular simulation methods in the design of ionic liquids to suit particular applications.