Synthesis and Photodynamic Effect of New Highly Photostable Decacationically Armed [60]- and [70]Fullerene Decaiodide Monoadducts To Target Pathogenic Bacteria and Cancer Cells

Novel water-soluble decacationically armed C-60 and C-70 decaiodide monoadducts, C-60- and C-70[>M(C3N6+C3)(2)], were synthesized, characterized, and applied as photosensitizers and potential nano-PDT agents against pathogenic bacteria and cancer cells. A high number of cationic charges per fullerene cage and H-bonding moieties were designed for rapid binding to the anionic residues displayed on the outer parts of bacterial cell walls. In the presence of a high number of electron-donating iodide anions as parts of quaternary ammonium salts in the arm region, we found that C-70[>M(C3N6+C3)(2)] produced more HO center dot than C-60[>M(C3N6+C3)(2)], in addition to O-1(2). This finding offers an explanation of the preferential killing of Gram-positive and Gram-negative bacteria by C-60[>M(C3N6+C3)(2)] and C-70[>M(C3N6+C3)(2)], respectively. The hypothesis is that O-1(2) can diffuse more easily into porous cell walls of Gram-positive bacteria to reach sensitive sites, while the less permeable Gram-negative bacterial cell wall needs the more reactive HO center dot to cause real damage.

On the diurnal cycle of urban aerosols, black carbon and the occurrence of new particle formation events in springtime Sao Paulo, Brazil

Large conurbations are a significant source of the anthropogenic pollution and demographic differences between cities that result in a different pollution burden. The metropolitan area of Sao Paulo (MASP, population 20 million) accounts for one fifth of the Brazilian vehicular fleet. A feature of MASP is the amount of ethanol used by the vehicular fleet, known to exacerbate air quality. The study describes the diurnal behaviour of the submicron aerosol and relies on total particle number concentration, particle number size distribution, light scattering and light absorption measurements. Modelled planetary boundary layer (PBL) depth and air mass movement data were used to aid the interpretation. During morning rush-hour, stagnant air and a shallow PBL height favour the accumulation of aerosol pollution. During clear-sky conditions, there was a wind shift towards the edge of the city indicating a heat island effect with implications on particulate pollution levels at the site. The median total particle number concentration for the submicron aerosol typically varied in the range 1.6 x 10(4)-3.2 x 10(4) cm(-3) frequently exceeding 4 x 10(4) cm-3 during the day. During weekdays, nucleation-mode particles are responsible for most of the particles by numbers. The highest concentrations of total particle number concentrations and black carbon (BC) were observed on Fridays. Median diurnal values for light absorption and light scattering (at 637 nm wavelength) varied in the range 12-33 Mm(-1) and 21-64 Mm(-1), respectively. The former one is equal to 1.8-5.0 mu g m(-3) of BC. The growth of the PBL, from the morning rush-hour until noon, is consistent with the diurnal cycle of BC mass concentrations. Weekday hourly median single-scattering albedo (omega(0)) varied in the range 0.59-0.76. Overall, this suggests a top of atmosphere (TOA) warming effect. However, considering the low surface reflectance of urban areas, for the given range of omega(0), the TOA radiative forcing can be either positive or negative for the sources within the MASP. On the average, weekend omega(0) values were 0.074 higher than during weekdays. During 11% of the days, new particle formation (NPF) events occurred. The analysed events growth rates ranged between 9 and 25 nm h(-1). Sulphuric acid proxy concentrations calculated for the site were less than 5% of the concentration needed to explain the observed growth. Thus, other vapours are likely contributors to the observed growth.

Synthesis and Solar Cell Application of New Alternating Donor-Acceptor Copolymers Based on Variable Units of Fluorene, Thiophene, and Phenylene

A new series of donor acceptor copolymers were synthesized via the Witting route and applied as an active layer in organic thin-films solar cells. These copolymers are composed of fluorene thiophene and phenylene thiophene units. The ratio between those was systematically varied, and copolymers containing 0%, 50%, and 75% of phenylene thiophene were characterized and evaluated when used in photovoltaic devices. The copolymers' composition, photophysical, electrical, and morphological properties are addressed and correlated with device performance. The 50% copolymer ratio was found to be the best copolymer of the series, yielding a power conversion efficiency (PCE) under air mass (AM) 1.5 conditions of 2.4% in the bilayer heterojunction with the C-60 molecule. Aiming at flexible electronics applications, solutions based on the heterojunction of this copolymer with PCBM (6,6-phenyl-C-61-butyric acid methyl ester) were also successfully deposited using an inkjet printing method and used as an active layer in solar cells.

Biocompatibility of New Calcium Aluminate Cement (Endo Binder)

Introduction: The purpose of this study was to evaluate the biocompatibility of calcium aluminate cement (EndoBinder) in subcutaneous tissue of rats. Methods: Fifteen rats, weighing 300 g, were separated into 3 groups (n = 5) in accordance with the time of death (7, 21, 42 days). Two incisions were made in the dorsal subcutaneous tissue of each rat in which were implanted 2 polyethylene tubes filled with the test materials, Endo Binder (EB) and Grey MTA (GMTA). The external tube walls were considered the negative control group (CG). After 7, 21, and 42 days, animals were killed, obtaining 5 samples per group, at each time interval of analysis. Results: From the morphologic and morphometric analyses by using a score of (0-3) (50, 100, and 400x), results showed absence of inflammatory reaction (0) for EB after 42 days. However, for GMTA, a slight inflammatory reaction (1) was observed after 42 days, which means the persistence of a chronic inflammatory process. When compared with CG, tissue reaction ranging from discrete (1-7 days) to absent (0-42 days) was observed. Conclusions: EndoBinder presented satisfactory tissue reaction; it was biocompatible when tested in subcutaneous tissue of rats. (J Endod 2012;38:367-371)

Design and synthesis of new (E)-cinnamic N-acylhydrazones as potent antitrypanosomal agents

We report herein the synthesis and trypanocidal profile of new (E)-cinnamic N-acylhydrazones (NAHs) designed by exploiting molecular hybridization between the potent cruzain inhibitors (E)-1-(benzo[d] 11,3)dioxol-5-yl)-3-(4-bromophenyl)prop-2-en-1-one and (E)-3-hydroxy-N'-((2-hydroxynaphthalen-1-yl)methylene)-7-methoxy-2-naphthohydrazide. These derivatives were evaluated against both amastigote and trypomastigote forms of Trypanosoma cruzi and lead us to identify two compounds that were approximately two times more active than the reference drug, benznidazole, and with good cytotoxic index. Although designed as cruzain inhibitors, the weak potency displayed by the best cinnamyl NAH derivatives indicated that another mechanism of action was likely responsible for their trypanocide action. (C) 2012 Elsevier Masson SAS. All rights reserved.

The antimicrobial effect of new and conventional endodontic irrigants on intra-orally infected dentin

Objectives. To evaluate if the incorporation of antimicrobial compounds to chelating agents or the use of chelating agents with antimicrobial activity as 7% maleic acid and peracetic acid show similar disinfection ability in comparison to conventional irrigants as sodium hypochlorite or iodine potassium iodide against biofilms developed on dentin. Materials and methods. The total bio-volume of live cells, the ratio of live cells and the substratum coverage of dentin infected intra-orally and treated with the irrigant solutions: MTAD, Qmix, Smear Clear, 7% maleic acid, 2% iodine potassium iodide, 4% peracetic acid, 2.5% and 5.25% sodium hypochlorite was measured by using confocal microscopy and the live/dead technique. Five samples were used for each irrigant solution. Results. Several endodontic irrigants containing antimicrobials as clorhexidine (Qmix), cetrimide (Smear Clear), maleic acid, iodine compounds or antibiotics (MTAD) lacked an effective antibiofilm activity when the dentin was infected intra-orally. The irrigant solutions 4% peracetic acid and 2.5–5.25% sodium hypochlorite decrease significantly the number of live bacteria in biofilms, providing also cleaner dentin surfaces (p < 0.05). Conclusions. Several chelating agents containing antimicrobials could not remove nor kill significantly biofilms developed on intra-orally infected dentin, with the exception of sodium hypochlorite and 4% peracetic acid. Dissolution ability is mandatory for an appropriate eradication of biofilms attached to dentin.

Two series of new semisynthetic triterpene derivatives: differences in anti-malarial activity, cytotoxicity and mechanism of action

Background The discovery and development of anti-malarial compounds of plant origin and semisynthetic derivatives thereof, such as quinine (QN) and chloroquine (CQ), has highlighted the importance of these compounds in the treatment of malaria. Ursolic acid analogues bearing an acetyl group at C-3 have demonstrated significant anti-malarial activity. With this in mind, two new series of betulinic acid (BA) and ursolic acid (UA) derivatives with ester groups at C-3 were synthesized in an attempt to improve anti-malarial activity, reduce cytotoxicity, and search for new targets. In vitro activity against CQ-sensitive Plasmodium falciparum 3D7 and an evaluation of cytotoxicity in a mammalian cell line (HEK293T) are reported. Furthermore, two possible mechanisms of action of anti-malarial compounds have been evaluated: effects on mitochondrial membrane potential (ΔΨm) and inhibition of β-haematin formation. Results Among the 18 derivatives synthesized, those having shorter side chains were most effective against CQ-sensitive P. falciparum 3D7, and were non-cytotoxic. These derivatives were three to five times more active than BA and UA. A DiOC6(3) ΔΨm assay showed that mitochondria are not involved in their mechanism of action. Inhibition of β-haematin formation by the active derivatives was weaker than with CQ. Compounds of the BA series were generally more active against P. falciparum 3D7 than those of the UA series. Conclusions Three new anti-malarial prototypes were obtained from natural sources through an easy and relatively inexpensive synthesis. They represent an alternative for new lead compounds for anti-malarial chemotherapy.

Modeling global pricing and launching of new drugs

Doctorado en Economía: Aplicaciones a las finanzas y seguros, a la economía sectorial, al medio ambiente y a las infraestructuras.

Design and development of new pressure sensors for aerodynamic applications

This artwork reports on two different projects that were carried out during the three years of Doctor of the Philosophy course. In the first years a project regarding Capacitive Pressure Sensors Array for Aerodynamic Applications was developed in the Applied Aerodynamic research team of the Second Faculty of Engineering, University of Bologna, Forlì, Italy, and in collaboration with the ARCES laboratories of the same university. Capacitive pressure sensors were designed and fabricated, investigating theoretically and experimentally the sensor’s mechanical and electrical behaviours by means of finite elements method simulations and by means of wind tunnel tests. During the design phase, the sensor figures of merit are considered and evaluated for specific aerodynamic applications. The aim of this work is the production of low cost MEMS-alternative devices suitable for a sensor network to be implemented in air data system. The last two year was dedicated to a project regarding Wireless Pressure Sensor Network for Nautical Applications. Aim of the developed sensor network is to sense the weak pressure field acting on the sail plan of a full batten sail by means of instrumented battens, providing a real time differential pressure map over the entire sail surface. The wireless sensor network and the sensing unit were designed, fabricated and tested in the faculty laboratories. A static non-linear coupled mechanical-electrostatic simulation, has been developed to predict the pressure versus capacitance static characteristic suitable for the transduction process and to tune the geometry of the transducer to reach the required resolution, sensitivity and time response in the appropriate full scale pressure input A time dependent viscoelastic error model has been inferred and developed by means of experimental data in order to model, predict and reduce the inaccuracy bound due to the viscolelastic phenomena affecting the Mylar® polyester film used for the sensor diaphragm. The development of the two above mentioned subjects are strictly related but presently separately in this artwork.

Synthetic and mechanistic investigation of new radical processes: reaction of organic azides with group-XIII Lewis acids

Dichloroindium hydride revealed to be a valid alternative to tributyltin hydride for radical reduction of organic (alkyl, aryl, acyl, solfonyl) azides. The new approach entails mild reaction conditions and provides high yields of the corresponding amines and amides, also showing high degrees of selectivity. The system dichloroindium hydride / azides can be utilised in fivemembered ring closures of g-azidonitriles, as a new source of aminyl radicals for the attractive synthesis of interesting amidine compounds in the absence of both toxic reagents and tedious purification procedures. Allylindium dichloride seems a good substitute for dichloroindium hydride for generation of indium centred radicals under photolytic conditions, since it allows allylation of electrophilic azides (e.g. phenylsulfonyl azide) and halogen or ester δ-substituted azides, the latter through a 1,5-H transfer rearrangement mechanism. Evidences of the radical nature of the reactions mechanism were provided by ESR spectroscopy, furthermore the same technique, allowed to discover that the reaction of azides with indium trichloride and other group XIII Lewis acids, in particular gallium trichloride, gives rise to strongly coloured, persistent paramagnetic species, whose structure is consistent with the radical cation of the head-to-tail dimer of the aniline corresponding to the starting azide.

Design and Characterization of New Luminescent Sensors and Labels

The aim of this Ph.D. project has been the design and characterization of new and more efficient luminescent tools, in particular sensors and labels, for analytical chemistry, medical diagnostics and imaging. Actually both the increasing temporal and spatial resolutions that are demanded by those branches, coupled to a sensitivity that is required to reach the single molecule resolution, can be provided by the wide range of techniques based on luminescence spectroscopy. As far as the development of new chemical sensors is concerned, as chemists we were interested in the preparation of new, efficient, sensing materials. In this context, we kept developing new molecular chemosensors, by exploiting the supramolecular approach, for different classes of analytes. In particular we studied a family of luminescent tetrapodal-hosts based on aminopyridinium units with pyrenyl groups for the detection of anions. These systems exhibited noticeable changes in the photophysical properties, depending on the nature of the anion; in particular, addition of chloride resulted in a conformational change, giving an initial increase in excimeric emission. A good selectivity for dicarboxylic acid was also found. In the search for higher sensitivities, we moved our attention also to systems able to perform amplification effects. In this context we described the metal ion binding properties of three photoactive poly-(arylene ethynylene) co-polymers with different complexing units and we highlighted, for one of them, a ten-fold amplification of the response in case of addition of Zn2+, Cu2+ and Hg2+ ions. In addition, we were able to demonstrate the formation of complexes with Yb3+ an Er3+ and an efficient sensitization of their typical metal centered NIR emission upon excitation of the polymer structure, this feature being of particular interest for their possible applications in optical imaging and in optical amplification for telecommunication purposes. An amplification effect was also observed during this research in silica nanoparticles derivatized with a suitable zinc probe. In this case we were able to prove, for the first time, that nanoparticles can work as “off-on” chemosensors with signal amplification. Fluorescent silica nanoparticles can be thus seen as innovative multicomponent systems in which the organization of photophysically active units gives rise to fruitful collective effects. These precious effects can be exploited for biological imaging, medical diagnostic and therapeutics, as evidenced also by some results reported in this thesis. In particular, the observed amplification effect has been obtained thanks to a suitable organization of molecular probe units onto the surface of the nanoparticles. In the effort of reaching a deeper inside in the mechanisms which lead to the final amplification effects, we also attempted to find a correlation between the synthetic route and the final organization of the active molecules in the silica network, and thus with those mutual interactions between one another which result in the emerging, collective behavior, responsible for the desired signal amplification. In this context, we firstly investigated the process of formation of silica nanoparticles doped with pyrene derivative and we showed that the dyes are not uniformly dispersed inside the silica matrix; thus, core-shell structures can be formed spontaneously in a one step synthesis. Moreover, as far as the design of new labels is concerned, we reported a new synthetic approach to obtain a class of robust, biocompatible silica core-shell nanoparticles able to show a long-term stability. Taking advantage of this new approach we also showed the synthesis and photophysical properties of core-shell NIR absorbing and emitting materials that proved to be very valuable for in-vivo imaging. In general, the dye doped silica nanoparticles prepared in the framework of this project can conjugate unique properties, such as a very high brightness, due to the possibility to include many fluorophores per nanoparticle, high stability, because of the shielding effect of the silica matrix, and, to date, no toxicity, with a simple and low-cost preparation. All these features make these nanostructures suitable to reach the low detection limits that are nowadays required for effective clinical and environmental applications, fulfilling in this way the initial expectations of this research project.