Publications

Abstract An experimental and computational study of the thermochemical and structural properties of ethylenethiourea (ETU) has been carried out. The enthalpies of combustion and sublimation, measured respectively by rotating-bomb combustion calorimetry and Calvet microcalorimetry, yielded the gas-phase enthalpy of formation of ETU at T = 298.15 K. This latter parameter was also derived from high-level molecular orbital calculations at the G3(MP2)//B3LYP level of theory, leading to a value in excellent agreement with the one obtained from experimental data. With the purpose of evaluating the influence of the ring size in the enthalpy of formation of cyclic N,N'-thiourea derivatives, the calculation of the enthalpy of formation of N,N'-trimethylenethiourea (MTU) was performed using the G3-(MP2)//B3LYP approach. The effects of substituents (carbonyl and thiocarbonyl) on the molecular stability of several N-alkyl (cyclic) ureas/thioureas were also studied.

Abstract This paper reports an experimental and theoretical study about the energetic and structural characteristics of the 2-mercaptobenzimidazole (MBI) tautomeric forms (thione and thiol). The standard (pA degrees A = 0.1 MPa) molar enthalpy of formation, at T = 298.15 K, in the gaseous phase, for MBI was derived from its enthalpies of combustion and sublimation, obtained by rotating-bomb calorimetry and by the Knudsen effusion technique, respectively. The results are compared with the corresponding data for MBI thione/thiol tautomers calculated by the G3(MP2)//B3LYP approach that suggest the thione form as the preferred form of MBI in gaseous phase. Computationally, the molecular structures of both tautomers were established and the geometrical parameters were determined at the B3LYP/6-31G(d) level of theory. In addiction, the G3(MP2)//B3LYP tautomerization energy at 0 K for thione/thiol forms of MBI was calculated and also evidences that the tautomeric equilibrium favours the thione tautomer. The standard Gibbs energy of formation in crystalline and gaseous phases was also derived, allowing an analysis of the thermodynamic stability of MBI in comparison with other related compounds.

Abstract A simple and expedite electrochemical methodology was developed for the determination of ciprofloxacin, based on a glassy carbon (GC) electrode modified by a combination of multi-walled carbon nanotubes (MWCNT) with -cyclodextrin (-CD) incorporated in a polyaniline film. The combined use of -CD and MWCNT in the electrochemical sensor leads to a significant signal improvement. The -CD/MWCNT modified GC electrode exhibited efficient electrocatalytic behavior in the oxidation of ciprofloxacin with relatively high sensitivity, stability and lifetime. Molecular modeling studies showed that ciprofloxacin binds preferably to -CD rather than to CNT edges, leading to an improved sensitivity of the sensor. Under optimized conditions, a linear calibration curve was obtained for ciprofloxacin in the concentration range 10-80 mu M with a detection limit of 50nM. The analytical performance of this sensor was evaluated for the detection of ciprofloxacin in a wastewater treatment plant effluent.

Abstract How can a work of art give us clues about scientific aspects? How can chemistry help a painter enhance his creativity and, above all, preserve the original characteristics of his work? Does an artist require scientific knowledge to innovate or, at least, not to be faked? Other symbiotic fields between art and science are: tattoos, as body art with physical and chemical consequences; pigments, as basic materials with interesting historiographical preparations; spectroscopy diagnosis, as very broad and thorough method of analysis (but also specific and non-intrusive); biosensors, as one of the applications of new pigments. Note also the interconnection between the several possible paths of science and art, which reflect new challenges with enormous potential investigated through a literature review and the application as a case study in an educational inquiry module.

Abstract The disinfection-induced and photo-induced degradation of the UV filter 3-methylbutyl-(2E)-3-(4-methoxyphenyl)-acrylate (IMC) is investigated. High performance liquid chromatography was used to follow the degradation reactions, determine kinetic features and also the influence of external variables on degradation [pH; temperature; chlorine concentration; dissolved organic matter (DOM) concentration]. Liquid chromatography preceded by solid-phase extraction, was used for the determination of by-products. IMC was found to rapidly and substantially degrade in aqueous solution, when in exposure to active chlorine, displaying a pseudo second-order degradation rate constant of 0.042 +/- 0.001 L mol(-1) s(-1), and a half-life period of 23.8 +/- 0.6 s. Contact with aqueous active chlorine proved to yield merely the dichlorinated form of IMC, as the prominent disinfection by-product. The assessment of influence of external variables on degradation, was insured by a Box-Behnken experimental design formulation approach, with factorial analysis. In this regard, data shows that temperature plays a decisive factor in the reaction rate, without DOM in solution, leading to decreasing degradation rates as the temperature increases. With DOM in solution, pH and DOM proved to be the most influential variables on IMC degradation. Regarding the photo-degradation study, results have shown that IMC remained quite stable in aqueous solution when exposed to artificial solar radiation, with a rate constant of 0.00073 +/- 0.00002 min(-1) and a half-life period of 938.5 +/- 31.1 min. This work addresses yet another filter that has never been studied, and hopes to provide clarification on its environmental fate and behaviour when in the aqueous environmental compartments.

Abstract Blood-brain barrier is a tightly packed layer of endothelial cells surrounding the brain that acts as the main obstacle for drugs enter the central nervous system (CNS), due to its unique features, as tight junctions and drug efflux systems. Therefore, since the incidence of CNS disorders is increasing worldwide, medical therapeutics need to be improved. Consequently, aiming to surpass blood-brain barrier and overcome CNS disabilities, silencing P-glycoprotein as a drug efflux transporter at brain endothelial cells through siRNA is considered a promising approach. For siRNA enzymatic protection and efficient delivery to its target, two different nanoparticles platforms, solid lipid (SLN) and poly-lactic-co-glycolic (PLGA) nanoparticles were used in this study. Polymeric PLGA nanoparticles were around 115 nm in size and had 50 % of siRNA association efficiency, while SLN presented 150 nm and association efficiency close to 52 %. Their surface was functionalized with a peptide-binding transferrin receptor, in a site-oriented manner confirmed by NMR, and their targeting ability against human brain endothelial cells was successfully demonstrated by fluorescence microscopy and flow cytometry. The interaction of modified nanoparticles with brain endothelial cells increased 3-fold compared to non-modified lipid nanoparticles, and 4-fold compared to non-modified PLGA nanoparticles, respectively. These nanosystems, which were also demonstrated to be safe for human brain endothelial cells, without significant cytotoxicity, bring a new hopeful breath to the future of brain diseases therapies.

Abstract Cancer is the major cause of morbidity and mortality worldwide. Hydroxycinnamic acids (HCAs) are naturally occurring compounds and their alkyl esters may possess enhanced biological activities. We evaluated C4, C14, C16, and C18 alkyl esters of p-coumaric, ferulic, sinapic, and caffeic acids (19 compounds) for their cytotoxic activity against four human cancer cells and also examined their effect on cell cycle alteration and apoptosis induction. The tetradecyl (1c) and hexadecyl (1d) esters of p-coumaric acid and tetradecyl ester of caffeic acid (4c), but not the parental HCAs, were selectively effective against MOLT-4 (human lymphoblastic leukemia) cells with IC50 values of 0.123 +/- 0.012, 0.301 +/- 0.069 and 1.0 +/- 0.1 mu M, respectively. Compounds 1c, 1d, and 4c significantly increased apoptotic cells in sub-G1 phase and activated the caspase-3 enzyme in MOLT-4 cells. Compound 1c was 15.4 and 23.6 times more potent than doxorubicin and cisplatin, respectively, against the drug resistant MES-SA-DX5 uterine sarcoma cells. These p-coumarate esters were several times less effective against NIH/3T3 fibroblast cells. Docking studies showed that 1c may cause cytotoxicity by interaction with carbonic anhydrase IX. In conclusion, long chain alkyl esters of p-coumaric acid are promising scaffolds for selective apoptosis induction in cancer cells.

Abstract Because of the lack of significant disease-modifying drugs for neurodegenerative disorders, a pressing need for new chemical entities endowed with IMAO-B still exists. Within this framework, and for the first time, a study was performed to compare coumarin- and chomone-3-phenylcarboxamide scaffolds. Compounds 10a and 10b were the most potent, selective, and reversible noncompetitive IMAO-B. The benzopyrone sp(2) oxygen atom was found to be position independent and a productive contributor for the ligand-enzyme complex stability.

Abstract Monoamine oxidase (MAO) is an enzyme responsible for metabolism of monoamine neurotransmitters which play an important role in brain development and function. This enzyme exists in two isoforms, and it has been demonstrated that MAO-B activity, but not MAO-A activity, increases with aging. MAO inhibitors show clinical value because besides the monoamine level regulation they reduce the formation of byproducts of the MAO catalytic cycle, which are toxic to the brain. A series of 2-phenylbenzofuran derivatives was designed, synthesized and evaluated against hMAO-A and hMAO-B enzymes. A bromine substituent was introduced in the 2-phenyl ring, whereas position 5 or 7 of the benzofuran moiety was substituted with a methyl group. Most of the tested compounds inhibited preferentially MAO-B in a reversible manner, with IC50 values in the low micro or nanomolar range. The 2-( 2'-bromophenyl)-5-methylbenzofuran ( 5) was the most active compound identified (IC50 = 0.20 mu M). In addition, none of the studied compounds showed cytotoxic activity against the human neuroblastoma cell line SH-SY5Y. Molecular docking simulations were used to explain the observed hMAO-B structure-activity relationship for this type of compounds.