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2020
Kordestani, N, Rudbari {HA}, Fernandes {AR}, Raposo {LR }, Baptista {PV}, Ferreira {DA }, Bruno G, Bella G, Scopelliti R, Braun {JD }, Herbert {DE }, Blacque O.  2020.  Antiproliferative Activities of Diimine-Based Mixed Ligand Copper(II) Complexes, feb. ACS Combinatorial Science. 22:89–99., Number 2: ACS - American Chemical Society Abstract

A series of Cu(diimine)(X-sal)(NO3) complexes, where the diimine is either 2,2′-bipyridine (bpy) or 1,10-phenanthroline (phen) and X-sal is a monoanionic halogenated salicylaldehyde (X = Cl, Br, I, or H), have been synthesized and characterized by elemental analysis and X-ray crystallography. Penta-coordinate geometries copper(II) were observed for all cases. The influence of the diimine coligands and different halogen atoms on the antiproliferative activities toward human cancer cell lines have been investigated. All Cu(II) complexes were able to induce a loss of A2780 ovarian carcinoma cell viability, with phen derivatives more active than bpy derivatives. In contrast, no in vitro antiproliferative effects were observed against the HCT116 colorectal cancer cell line. These cytotoxicity differences were not due to a different intracellular concentration of the complexes determined by inductively coupled plasma atomic emission spectroscopy. A small effect of different halogen substituents on the phenolic ring was observed, with X = Cl being the most highly active toward A2780 cells among the phen derivatives, while X = Br presented the lowest IC50 in A2780 cells for bpy analogs. Importantly, no reduction in normal primary fibroblasts cell viability was observed in the presence of bpy derivatives (IC50 > 40 μM). Mechanistically, complex 1 seems to induce a stronger apoptotic response with a higher increase in mitochondrial membrane depolarization and an increased level of intracellular reactive oxygen species (ROS) compared to complex 3. Together, these data and the low IC50 compared to cisplatin in A2780 ovarian carcinoma cell line demonstrate the potential of these bpy derivatives for further in vivo studies.

Pacheco, RM, Jacinto JP, Penas D, Calmeiro T, Almeida A, Colaco M, Fortunato E, Jones NC, Hoffmann, V S, Pereira MMA, Tavares P, Pereira AS.  2020.  Supramolecular protein polymers using mini-ferritin Dps as the building block, DEC 7. ORGANIC & BIOMOLECULAR CHEMISTRY. 18:9300-9307., Number 45 Abstract

A missense mutant of a Dps protein (DNA-binding protein from starved cells) from Marinobacter hydrocarbonoclasticus was used as a building block to develop a new supramolecular assembly complex which enhances the iron uptake, a physiological function of this mini-ferritin. The missense mutation was conducted in an exposed and flexible region of the N-terminal, wherein a threonine residue in position 10 was replaced by a cysteine residue (DpsT10C). This step enabled a click chemistry approach to the variant DpsT10C, where a thiol-ene coupling occurs. Two methods and two types of linker were used resulting in two different mini-ferritin supramolecular polymers, which have maintained secondary structure and native iron uptake physiological function. Electrophoretic assays and mass spectrometry were utilized to confirm that both functionalization and coupling reactions occured as predicted. The secondary structure has been investigated by circular dichroism and synchrotron radiation circular dichroism. Size and morphology were obtained by dynamic light scattering, size exclusion chromatography and atomic force microscopy, respectively. The iron uptake of the synthesized protein polymers was confirmed by UV-Vis spectroscopy loading assays.

Kordestani, N, Rudbari HA, Fernandes AR, Raposo LR, Baptista PV, Ferreira D, Bruno G, Bella G, Scopelliti R, Braun JD, Herbert DE, Blacque O.  2020.  Antiproliferative Activities of Diimine-Based Mixed Ligand Copper(II) Complexes, 2020. ACS Comb Sci. 22(2):89-99. AbstractWebsite

A series of Cu(diimine)(X-sal)(NO3) complexes, where the diimine is either 2,2'-bipyridine (bpy) or 1,10-phenanthroline (phen) and X-sal is a monoanionic halogenated salicylaldehyde (X = Cl, Br, I, or H), have been synthesized and characterized by elemental analysis and X-ray crystallography. Penta-coordinate geometries copper(II) were observed for all cases. The influence of the diimine coligands and different halogen atoms on the antiproliferative activities toward human cancer cell lines have been investigated. All Cu(II) complexes were able to induce a loss of A2780 ovarian carcinoma cell viability, with phen derivatives more active than bpy derivatives. In contrast, no in vitro antiproliferative effects were observed against the HCT116 colorectal cancer cell line. These cytotoxicity differences were not due to a different intracellular concentration of the complexes determined by inductively coupled plasma atomic emission spectroscopy. A small effect of different halogen substituents on the phenolic ring was observed, with X = Cl being the most highly active toward A2780 cells among the phen derivatives, while X = Br presented the lowest IC50 in A2780 cells for bpy analogs. Importantly, no reduction in normal primary fibroblasts cell viability was observed in the presence of bpy derivatives (IC50 > 40 muM). Mechanistically, complex 1 seems to induce a stronger apoptotic response with a higher increase in mitochondrial membrane depolarization and an increased level of intracellular reactive oxygen species (ROS) compared to complex 3. Together, these data and the low IC50 compared to cisplatin in A2780 ovarian carcinoma cell line demonstrate the potential of these bpy derivatives for further in vivo studies.

Machado, JF, Sequeira D, Marques F, Piedade MFM, Villa de Brito MJ, Helena Garcia M, Fernandes AR, Morais TS.  2020.  New copper(I) complexes selective for prostate cancer cells, 2020. Dalton Trans. 49(35):12273-12286. AbstractWebsite

A new family of eighteen Cu(i) complexes of the general formula [Cu(PP)(LL)][BF4], where PP is a phosphane ligand and LL represents an N,O-heteroaromatic bidentate ligand, has been synthesized and fully characterized by classical analytical and spectroscopic methods. Five complexes of this series were also characterized by single crystal X-ray diffraction studies. The cytotoxicity of all compounds was evaluated in breast (MCF7) and prostate (LNCap) human cancer cells and in a normal prostate cell line (RWPE). In general, all compounds showed higher cytotoxicity for the prostate cancer cells than for the breast cells, with IC50 values in the range 0.2-2 muM after 24 h of treatment. The most cytotoxic compound, [Cu(dppe)(2-ap)][BF4] (16), where dppe = 1,2-bis(diphenylphosphano) ethane and 2-ap = 2-acetylpyridine, showed a high level of cellular internalization, generation of intracellular ROS and activation of the cell death mechanism via apoptosis/necrosis. Owing to its high cytotoxic activity for LNCap cells, being 70-fold higher than that for normal prostate cells (RWPE), complex (16) was found to be the most promising for further research in prostate cancer models.

Trindade, AC, Carreto M, Helgesen G, Knudsen KD, Puchtler F, Breu J, Fernandes S, Godinho MH, Fossum JO.  2020.  Photonic composite materials from cellulose nanorods and clay nanolayers, 2020. 229(17):2741-2755. AbstractWebsite

Cellulose nano crystals (CNCs) are promising materials for energy efficient buildings related to the control of reflectivity and heat absorption/reflection of light. In this sense it is important to improve CNCs films fire retardant properties, which can be achieved by adding clays. Cellulose nanocrystals (CNCs) and nanolayers obtained from Sodium Fluorohectorite (NaFh) synthetic clay are both known to form liquid crystalline phases in aqueous suspensions. CNCs form cholesteric phases, which structure is preserved after water evaporation, while dry NaFh nanolayers aligned films collapse. In this initial work, it is shown that CNCs are compatible with NaFh clay. We demonstrate that the liquid crystalline phase of CNCs in water is not destroyed by the presence of NaFh nanolayers. The NaFh nanolayers act as planar anchoring surfaces to the cellulose nanorods and, after evaporation of the water coloured films are obtained. The precursor solutions and the photonic films were investigated by Describe several techniques.

Das, K, Datta A, Frontera A, Wen YS, Roma-Rodrigues C, Raposo LR, Fernandes AR, Hung CH.  2020.  Zn(II) and Co(II) derivatives anchored with scorpionate precursor: Antiproliferative evaluation in human cancer cell lines, 2020. J Inorg Biochem. 202:110881. AbstractWebsite

A 'scorpionate' type precursor [bdtbpza=bis(3,5-di-t-butylpyrazol-1-yl)acetate] has been employed to synthesize two mononuclear Zn(II) and Co(II) derivatives, namely [Zn(bdtbpza)2 (H2O)2].2.5CH3OH.2[(CH3)3C-C3H2N2-C(CH3)3] (1) and [Co(bdtbpza)2(CH3OH)4] (2) in good yield. Single crystal X-ray diffraction analysis reveals that in 1, the Zn(II) atom is tetrahedrally surrounded by a pair of Oacetate atoms of two bis(pyrazol-1-yl)acetate units and two water molecules; while in 2, the Co(II) atom shows an octahedral environment coordinating a pair of Oacetate atoms of two bis(pyrazol-1-yl)acetate units along with four methanol molecules. The EPR spectra of 2 recorded at 77 and 298K confirmed the tetragonal symmetry of the high spin Co(II). The DFT (Density functional theory) computation is in good agreement with the geometry proposed for compounds 1 and 2. Both the compounds display a high antiproliferative activity against HCT116 (colorectal carcinoma) and A2780 (ovarian carcinoma) cell lines compared to human normal dermal fibroblasts. In the case of A2780 cells, compounds 1 and 2 exhibit IC50 values that are similar to those described for cisplatin, a widely used chemotherapeutic drug. Exposure of A2780 cells to the IC50 concentration of each compound led to an increase of the number of apoptotic and autophagic cells. In the case of compound 1, the accumulation of intracellular ROS (Reactive oxygen species) is responsible for triggering A2780 cell death.

Roque, ACA, Pina AS, Azevedo AM, Aires-Barros R, Jungbauer A, Profio DG, Heng JYY, Haigh J, Ottens M.  2020.  Anything but Conventional Chromatography Approaches in Bioseparation. Biotechnology Journal. (e1900274):1-8.
Strohmeier, P, Honnet C, Perner-Wilson H, Teyssier M, Fruchard B, Baptista AC, Steimle J.  2020.  Demo of PolySense: How to Make Electrically Functional Textiles. CHI Conference on Human Factors in Computing Systems. :1-4. Abstract

We demonstrate a simple and accessible method for enhancing textiles with custom piezo-resistive properties. Based on in-situ polymerization, our method offers seamless integration at the material level, preserving a textile's haptic and mechanical properties. We demonstrate how to enhance a wide set of fabrics and yarns using only readily available tools. During each demo session, conference attendees may bring textile samples which will be polymerized in a shared batch. Attendees may keep these samples. While the polymerization is happening, attendees can inspect pre-made samples and explore how these might be integrated in functional circuits. Examples objects created using polymerization include rapid manufacturing of on-body interfaces, tie-dyed motion-capture clothing, and zippers that act as potentiometers.

Haque, S, Alexandre M, Mendes MJ, Águas H, Fortunato E, Martins R.  2020.  Design of wave-optical structured substrates for ultra-thin perovskite solar cells. Applied Materials Today. 20(100720)
Li, K, Haque S, Martins A, Fortunato E, Martins R, Mendes MJ, Schuster CS.  2020.  Light trapping in solar cells: simple design rules to maximize absorption. Optica. 7(10):1377-1384.
Honnet, C, Perner-Wilson H, Teyssier M, Fruchard B, Steimle J, Baptista AC, Strohmeier P.  2020.  PolySense: Augmenting Textiles with Electrical Functionality using In-Situ Polymerization. Proceedings of the 2020 CHI Conference on Human Factors in Computing Systems.
Strohmeier, P, Honnet C, Pernet-Wilson H, Teyssier M, Fruchard B, Baptista AC, Steimle J.  2020.  PolySense: How to Make Electrically Functional Textiles. CHI Conference on Human Factors in Computing Systems .
https://www.mdpi.com/2673-3978/2/1/1/htm.  2020.  Ta2O5/SiO2 Multicomponent Dielectrics for Amorphous Oxide TFTs . Electronic Materials. 2(1)
Mendes, MJ, Sanchez-Sobrado O, Haque S, Mateus T, Águas H, Fortunato E, Martins R.  2020.  Wave-optical front structures on silicon and perovskite thin-film solar cells. Solar Cells and Light Management: Materials, Strategies and Sustainability. :315-354., Amsterdam: Elsevier
Chabert, V, Babel L, Füeg MP, Karamash M, Madivoli ES, Herault N, Dantas JM, Salgueiro CA, Giese B, Fromm KM.  2020.  Kinetics and Mechanism of Mineral Respiration: How Iron Hemes Synchronize Electron Transfer Rates. Angewandte Chemie International Edition. 59:12331-12336., Number 30 AbstractWebsite

Abstract Anaerobic microorganisms of the Geobacter genus are effective electron sources for the synthesis of nanoparticles, for bioremediation of polluted water, and for the production of electricity in fuel cells. In multistep reactions, electrons are transferred via iron/heme cofactors of c-type cytochromes from the inner cell membrane to extracellular metal ions, which are bound to outer membrane cytochromes. We measured electron production and electron flux rates to 5×105 e s−1 per G. sulfurreducens. Remarkably, these rates are independent of the oxidants, and follow zero order kinetics. It turned out that the microorganisms regulate electron flux rates by increasing their Fe2+/Fe3+ ratios in the multiheme cytochromes whenever the activity of the extracellular metal oxidants is diminished. By this mechanism the respiration remains constant even when oxidizing conditions are changing. This homeostasis is a vital condition for living systems, and makes G. sulfurreducens a versatile electron source.

2019
Vaz, F, Kounatidis I, Covas G, Parton RM, Harkiolaki M, Davis I, Filipe* SR, Ligoxygakis* P.  2019.  Accessibility to peptidoglycan is important for recognition of Gram-positive bacteria in Drosophila. Cell Reports. 27(8):2480-2492.
Cristovão, AF, Sousa D, Silvestre F, Ropio I, Gaspar A, Henriques C, Velhinho A, Baptista AC, Faustino M, Ferreira I.  2019.  Customized tracheal design using 3D printing of a polymer hydrogel: influence of UV laser cross-linking on mechanical properties. 3D Printing in Medicine. 5:12. AbstractWebsite

Background
The use of 3D printing of hydrogels as a cell support in bio-printing of cartilage, organs and tissue has attracted much research interest. For cartilage applications, hydrogels as soft materials must show some degree of rigidity, which can be achieved by photo- or chemical polymerization. In this work, we combined chemical and UV laser polymeric cross-linkage to control the mechanical properties of 3D printed hydrogel blends. Since there are few studies on UV laser cross-linking combined with 3D printing of hydrogels, the work here reported offered many challenges.

Methods
Polyethylene glycol diacrylate (PEGDA), sodium alginate (SA) and calcium sulphate (CaSO4) polymer paste containing riboflavin (vitamin B2) and triethanolamine (TEOHA) as a biocompatible photoinitiator was printed in an extrusion 3D plotter using a coupled UV laser. The influence of the laser power on the mechanical properties of the printed samples was then examined in unconfined compression stress-strain tests of 1 × 1 × 1 cm3 sized samples. To evaluate the adhesion of the material between printed layers, compression measurements were performed along the parallel and perpendicular directions to the printing lines.

Results
At a laser density of 70 mW/cm2, Young’s modulus was approximately 6 MPa up to a maximum compression of 20% in the elastic regime for both the parallel and perpendicular measurements. These values were within the range of biological cartilage values. Cytotoxicity tests performed with Vero cells confirmed the cytocompatibility.

Conclusions
We printed a partial tracheal model using optimized printing conditions and proved that the materials and methods developed may be useful for printing of organ models to support surgery or even to produce customized tracheal implants, after further optimization.

Cristovão, AF, Sousa D, Silvestre F, Ropio I, Gaspar A, Henriques C, Velhinho A, Baptista AC, Faustino M, Ferreira I.  2019.  Customized tracheal design using 3D printing of a polymer hydrogel: influence of UV laser cross-linking on mechanical properties. 3D Print Med. 5:12.
Esteves C, Santos GMC, Alves C, Palma S, Porteira AR, Filho J, HA C, Alves VD, Faustino BMM, Ferreira I, Gamboa H, Roque ACA.  2019.  Effect of film thickness in gelatin hybrid gels for artificial olfaction. Materials Today Bio. 1:-. AbstractPDFWebsite

Artificial olfaction is a fast-growing field aiming to mimic natural olfactory systems. Olfactory systems rely on a first step of molecular recognition in which volatile organic compounds (VOCs) bind to an array of specialized olfactory proteins. This results in electrical signals transduced to the brain where pattern recognition is performed. An efficient approach in artificial olfaction combines gas-sensitive materials with dedicated signal processing and classification tools. In this work, films of gelatin hybrid gels with a single composition that change their optical properties upon binding to VOCs were studied as gas-sensing materials in a custom-built electronic nose. The effect of films thickness was studied by acquiring signals from gelatin hybrid gel films with thicknesses between 15 and 90 μm when exposed to 11 distinct VOCs. Several features were extracted from the signals obtained and then used to implement a dedicated automatic classifier based on support vector machines for data processing. As an optical signature could be associated to each VOC, the developed algorithms classified 11 distinct VOCs with high accuracy and precision (higher than 98%), in particular when using optical signals from a single film composition with 30 μm thickness. This shows an unprecedented example of soft matter in artificial olfaction, in which a single gelatin hybrid gel, and not an array of sensing materials, can provide enough information to accurately classify VOCs with small structural and functional differences.

Vieira, T, Silva JC, do Rego BAM, Borges JB, Henriques C.  2019.  Electrospun biodegradable chitosan based-poly(urethane urea) scaffolds for soft tissue engineering. Materials Science and Engineering: C. 103:109819. AbstractWebsite

The composition and architecture of a scaffold determine its supportive role in tissue regeneration. In this work, we demonstrate the feasibility of obtaining a porous electrospun fibrous structure from biodegradable polyurethanes (Pus) synthesized using polycaprolactone-diol as soft segment and, as chain extenders, chitosan (CS) and/or dimethylol propionic acid. Fourier transform infrared spectroscopy and proton nuclear magnetic resonance confirmed the syntheses. Fibre mats' properties were analysed and compared with those of solvent cast films. Scanning electron microscopy images of the electrospun scaffolds revealed fibres with diameters around 1 μm. From tensile tests, we found that Young's modulus increases with CS content and is higher for films (2.5 MPa to 6.5 MPa) than for the corresponding fibre mats (0.8 MPa to 3.2 MPa). The use of CS as the only chain extender improves recovery ratio and resilience. From X-ray diffraction, a higher crystalline degree was identified in fibre mats than in the corresponding films. Films' wettability was enhanced by the presence of CS as shown by the decrease of water contact angle. X-ray photoelectron spectroscopy revealed that while ester groups are predominant at the films' surface, ester and urethanes are present in similar concentrations at fibres' surface, favouring the interaction with water molecules. Both films and fibres undergo hydrolytic degradation. In vitro evaluation was performed with human dermal fibroblasts. No PU sample revealed cytotoxicity. Cells adhered to fibre mats better than to films and proliferation was observed only for samples of CS-containing PUs. Results suggest that electrospun fibres of CS-based polyurethanes are good candidate scaffolds for soft tissue engineering.

Kiazadeh, A, Deueurmeier J.  2019.  Flexible and transparent ReRAM devices for system on panel (SOP) application. Advances in Non-Volatile Memory and Storage Technology (Second Edition). (https://doi.org/10.1016/B978-0-08-102584-0.00014-0, Ed.).:519-538., Cambridge: Woodhead-Elsevier
Sanchez-Sobrado, O, Mendes MJ, Haque S, Mateus T, Aguas H, Fortunato E, Martins R.  2019.  Lightwave trapping in thin film solar cells with improved photonic-structured front contacts. Journal of Materials Chemistry C. 7(21):6456-6464.
Gavinho, SR, Prezas PR, Ramos DJ, Sá-Nogueira I, Borges JB, Lança CM, Silva JC, Henriques C, Pires E, Kumar JS, Graça MP.  2019.  Nontoxic glasses: Preparation, structural, electrical and biological properties. Applied Ceramics Technology. 16(5):1885-1894. AbstractWebsite

Bacterial infections affect about 1 in 5 patients who receive a dental implant within 5 years of surgery. To avoid the implant rejection it is necessary for the development of innovative biomaterials, with addition or substitution of the ions, for implant coatings that promote a strong bond with the new host bone and antibacterial action. The objective of this work was to synthesize a bioactive glass with different silver concentrations to evaluate their antibacterial performance. The glasses were synthesized with up to 2% silver content by melt-quenching. Structural, morphological, biological, and electrical properties of all samples were studied. The biological behavior was evaluated through cytotoxicity tests and antibacterial activity. The structural analysis shows that the introduction of silver do not promote significant changes, not altering the advantageous properties of the bioglass of the bioglass. It was verified that the glasses with a silver content from 0.5% to 2%, completely prevented the growth of both Staphylococcus aureus and Escherichia coli while being nontoxic toward mammalian cells. Therefore, these bioglasses are promising materials to be used in the production of dental implants with antimicrobial activity.

Alexandre, M, Chapa M, Haque S, Mendes MJ, Águas H, Fortunato E, Martins R.  2019.  Optimum Luminescent Down-Shifting Properties for High Efficiency and Stable Perovskite Solar Cells. ACS Applied Energy Materials. 2(4):2930–2938.
Haque, S, Mendes MJ, Sanchez-Sobrado O, Águas H, Fortunato E, Martins R.  2019.  Photonic-structured TiO2 for high-efficiency, flexible and stable Perovskite solar cells. Nano Energy. 59:91-101.
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