Publications

Abstract The crystal structures of two chromone derivatives, viz. ethyl 6-(4-methylphenyl)-4-oxo-4H-chromene-2-carboxylate, C19H16O4, (1), and ethyl 6-(4-fluorophenyl)-4-oxo-4H-chromene-2-carboxylate C18H13FO4, (2), have been determined: (1) crystallizes with two molecules in the asymmetric unit. A comparison of the dihedral angles beween the mean planes of the central chromone core with those of the substituents, an ethyl ester moiety at the 2-position and a para-substituted phenyl ring at the 6-position shows that each molecule differs significantly from the others, even the two independent molecules (a and b) of (1). In all three molecules, the carbonyl groups of the chromone and the carboxylate are trans-related. The supramolecular structure of (1) involves only weak C-H center dot center dot center dot pi interactions between H atoms of the substituent phenyl group and the phenyl group, which link molecules into a chain of alternating molecules a and b, and weak pi-pi stacking interactions between the chromone units. The packing in (2) involves C-H center dot center dot center dot O interactions, which form a network of two intersecting ladders involving the carbonyl atom of the carboxylate group as the acceptor for H atoms at the 7-position of the chromone ring and from an ortho-H atom of the exocyclic benzene ring. The carbonyl atom of the chromone acts as an acceptor from a meta-H atom of the exocyclic benzene ring. pi-pi interactions stack the molecules by unit translation along the a axis.

Abstract This work reports the experimental determination of relevant thermophysical properties of five halogenated fluorenes. The vapor pressures of the compounds studied were measured at different temperatures using two different experimental techniques. The static method was used for studying 2-fluorofluorene (liquid and crystal vapor pressures between 321.04 K and 411.88 K), 2-iodofluorene (liquid and crystal vapor pressures between 362.63 K and 413.86 K), and 2,7-dichlorofluorene (crystal vapor pressures between 364.64 K and 394.22 K). The Knudsen effusion method was employed to determine the vapor pressures of 2,7-difluorofluorene (crystal vapor pressures between 299.17 K and 321.19 K), 2,7-diiodofluorene (crystal vapor pressures between 393.19 K and 415.14 K), and (again) 2-iodofluorene (crystal vapor pressures between 341.16 K and 361.12 K). The temperatures and the molar enthalpies of fusion of the five compounds were determined using differential scanning calorimetry. The application to halogenated fluorenes of recently developed methods for predicting vapor pressures and enthalpies of sublimation and vaporization of substituted benzenes is also discussed.

Abstract The first potent and selective hA(1)AR ligand based on the chromone scaffold is reported in this work. Receptor-driven molecular modeling studies provide valuable information about the molecular interactions responsible for the high affinity of N-(2-nitrophenyl)-4-oxo-4H-chromene-2-carboxamide to the hA(1)AR (K-i = 0.219 mu M) and reinforce the crucial role of AR affinity of the amide linker located at C-2 of the pyrone ring.

Abstract Microalgae and cyanobacteria have received ample attention in the last few decades due to their environmental and biotechnological applications. Co-cultures of these microorganisms may present benefits particularly on wastewater bioremediation and biomass production. However, the understanding on the interactions between photosynthetic microorganisms is still in an early stage of knowledge. In this line, the aim of the present study was the evaluation of the growth dynamics of co-cultures of a cyanobacterium, Synechocystis salina, and a microalga, Pseudokirchneriella subcapitata, under low phosphate-phosphorus concentrations. Kinetic growth parameters were determined through the Monod and modified Gompertz models and evidence of allelochemical production was confirmed through metabolomic analysis of the supernatant obtained from the co-cultures using GC-MS and 1D-NMR. Kinetic growth parameters have shown that P. subcapitata was better adapted to grow under low phosphorus concentrations. Co-cultivation of these microorganisms did not influence P. subcapitata growth; however, S. salina growth was strongly inhibited. The modified Gompertz model has shown that growth inhibition of S. salina in co-cultures may be related to the activity of allelochemicals produced by P. subcapitata. This assumption was corroborated by the assessment of the antimicrobial potential of lactic acid (2-hydroxypropanoic acid), an organic acid identified in the supernatant from the co-cultures with growth inhibitory effects against S. salina.

Abstract The discovery of new chemical entities endowed with potent, selective, and reversible monoamine oxidase B inhibitory activity is a clinically relevant subject. Therefore, a small library of chromone derivatives was synthesized and screened toward human monoamine oxidase isoforms (hMAO-A and hMAO-B). The structure-activity relationships studies strengthen the importance of the amide spacer and the direct linkage of carbonyl group to the gamma-pyrone ring, along with the presence of meta and para substituents in the exocyclic ring. The most potent MAO-B inhibitors were N-(3'-chlorophenyl)-4-oxo-4H-chromene-3-carboxamide (20) (IC50 = 403 pM) and N-(3',4'-dimethylphenyl)-4-oxo-4H-chromene-3-carboxamide (27) (IC50 = 669 pM), acting as competitive and noncompetitive reversible inhibitors, respectively. Computational docking studies provided insights into enzyme-inhibitor interactions and a rationale for the observed selectivity and potency. Compound 27 stands out due to its favorable toxicological profile and physicochemical properties, which pointed toward blood-brain barrier permeability, thus being a valid candidate for subsequent animal studies.

Abstract The development of new chemical entities represents an important challenge in pharmaceutical industry, being the use of privileged scaffolds for library design and drug discovery a valuable approach. Among the panoply of privileged structures, our research group has focused its attention on the chromone (4H-benzopyran-4-one) scaffold due to its chemical versatility and ability to bind to multiple targets. With this endeavour we report an expedite two-step procedure for the synthesis of novel 6-aryl/heteroaryl-4-oxo-4H-chromene-2-carboxylic ethyl ester. The new chromones were synthesized by a C-C Suzuki cross-coupling microwave-assisted reaction, using Pd(OAc)(2) as a catalyst, and a classic Claisen condensation followed by an intramolecular cyclization process.

Abstract The development of fast and reliable methods for protein determination are of great relevance to a diversity of areas from industry to diagnostics. Molecular Imprinted Materials (MIM) has proved to be an interesting methodology for protein analysis however further studies of the effect of the experimental parameters and starting materials in the performance of the MIM are still required. Caffeic acid (CAF) is employed for the first time as a monomer to tailor a synthetic receptor for a protein target. This was done by bulk-electropolymerization, applying a constant potential of +2.0 V, for 30 s, on a carbon screen printed electrode, immersed in a solution of protein and CAF prepared in phosphate buffer. Annexin A3 (ANXA3) was selected as protein target due to the fact that this is an emerging biomarker in prostate cancer. The assembly of the protein imprinted material (PIM) was followed by Electrochemical Impedance Spectroscopy (EIS) and Raman Spectroscopy. A non-imprinted material (NIM) was prepared in parallel as control. Square wave voltammetry (SWV) was used to monitor the electrochemical signal of the [Fe(CN)(6)](3-)/[Fe(CN)(6)](4-) redox for the quantification of ANXA3. The optimized PIM-based device showed average detection limits (LOD) of 0.095 ng/mL, a linear behavior against log (concentration) between 0.10, and 200 ng/mL and good selectivity. The NIM-based device showed random behavior against protein concentration. Finally, the PIM-sensor was successfully applied to the analysis of ANXA3 in spiked urine samples.

Abstract Compared to the oil-derived plastics typically used in food packaging, biofilms of pure chitosan present serious moisture issues. The physical degradation of the polysaccharide with ultrasound effectively reduces the water vapor permeability in these films but, unfortunately, they also turn more brittle. Blending chitosans of different morphology and molecular mass (M) is an unexplored strategy that could bring balance without the need of incorporating toxic or non-biodegradable plasticizers. To this end, we prepared and characterized the mixtures of a high-M chitosan with the products of its own ultrasonic fragmentation. Biopolymer degradation was followed by dynamic light scattering (DLS) and the mechanical and structural characteristics of the mixtures were evaluated from different rheological methods and atomic force microscopy (AFM). The results indicate that, through the control of the sonication time and mixture ratio, it is possible to adjust the viscoelasticity and morphological aspect of the mixtures at intermediate levels relative to their individual components. In a more general sense, it is emphasized the importance of design and materials processing for the development of a novel generation of additive-free sustainable but functional bioplastics.

Abstract Purpose: There is nowadays extensive experimental and computational investigation on the pathophysiology of atherosclerosis, searching correlations between its focal nature and local hemodynamic environment. The goal of this work is to present a methodology for patient-specific hemodynamics study of the carotid artery bifurcation based on the use of ultrasound (US) morphological and blood flow velocity patient data. Materials/methods: Subject-specific studies were performed for two patients, using a developed finite element code. Geometrical models were obtained from the acquisition of longitudinal and sequential cross-sectional ultrasound images and boundary conditions from Doppler velocity measurements at the common carotid artery. Results: There was a good agreement between ultrasound imaging data and computational simulated results. For a normal and a stenosed carotid bifurcation the velocity, wall shear stress (WSS) and WSS descriptors analysis illustrated the extremely complex hemodynamic behavior along the cardiac cycle. Different patterns were found, associated with morphology and hemodynamic patient-specific conditions. High values of time-averaged WSS (TAWSS) were found at stenosis site and for both patients TAWSS fields presented low values within areas of high oscillating shear index and relative residence time values, corresponding to recirculation zones. Conclusion: Simulated hemodynamic parameters were able to capture the disturbed flow conditions in a normal and a stenosed carotid artery bifurcation, which play an important role in the development of local atherosclerotic plaques. Computational simulations based on clinic US might help improving diagnostic and treatment management of carotid atherosclerosis.

Abstract A strategy based on water-in-oil emulsion for the dispersion of a sol-gel mixture into small droplets was employed with the view of the production of naproxen-imprinted micro- and nanospheres. The procedure, aiming at a surface imprinting process, comprised the synthesis of a naproxen-derived surfactant. The imprinting process occurred at the interface of the emulsions or microemulsions, by the migration of the NAP-surfactant head into the sol-gel drops to leave surficial imprints due mainly to ion-pair interaction with a cationic group contained within the growing sol-gel network. The surface imprinted microspheric particles exhibited a log-normal size distribution with geometric mean diameter of 3.1 mu m. Amesoporous texture was found from measurements of the specific surface area (206 m(2)/g) and pore diameter (D-P 2 nm). Evaluation of the microspheres as packed HPLC stationary phases resulted in the determination of the selectivity factor against ibuprofen (alpha=2.1), demonstrating the successful imprinting. Chromatographic efficiency, evaluated by the number of theoretical plates (222 plates cm(-3)), emerged as an outstanding feature among the set of all relatable formats produced before, an advantage intrinsic to the location of the imprinted sites on the surface. The material presented a capacity of 3.2 mu mol g(-1). Additionally, exploratory work conducted on their nanoscale counterparts resulted in the production of nanospheres in the size order of 10 nm providing good indications of a successful imprinting process.