Browsing by Author "Garcia, M. Helena"
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- Benzo[c]thiophene chromophores linked to cationic Fe and Ru derivatives for NLO materials: synthesis characterization and quadratic hyperpolarizabilitiesPublication . Silva, Tiago J. L.; Mendes, Paulo J.; Garcia, M. Helena; Robalo, Maria Paula; Ramalho, J. P. Prates; Carvalho, A. J. Palace; Buechert, Marina; Wittenburg, Christian; Heck, Juergen5-Monocyclopentadienyliron(II)/ruthenium(II) complexes of the general formula [M(5-C5H5)(PP)(L1)][PF6] {M = Fe, PP = dppe; M = Ru, PP = dppe or 2PPh3; L1 = 5-[3-(thiophen-2-yl)benzo[c]thiophenyl]thiophene-2-carbonitrile} have been synthesized and studied to evaluate their molecular quadratic hyperpolarizabilities. The compounds were fully characterized by NMR, FTIR and UV/Vis spectroscopy and their electrochemical behaviour studied by cyclic voltammetry. Quadratic hyperpolarizabilities () were determined by hyper-Rayleigh scattering measurements at a fundamental wavelength of 1500 nm. Density functional theory calculations were employed to rationalize the second-order non-linear optical properties of these complexes.
- Biological activity and cellular uptake of [Ru(eta(5)-C5H5)(PPh3)(Me(2)bpy)][CF3SO3] complexPublication . Morais, Tania S.; Santos, Filipa; Côrte-Real, Leonor; Marques, Fernanda; Robalo, Maria Paula; Paulo J. Amorim Madeira; Garcia, M. HelenaAnticancer activity of the new [Ru(eta(5)-C5H5)(PPh3)(Me(2)bpy)][CF3SO3] (Me(2)bpy = 4,4'-dimethyl-2,2'-bipyridine) complex was evaluated in vitro against several human cancer cell lines, namely A2780, A2780CisR, HT29, MCF7, MDAMB231 and PC3. Remarkably, the IC50 values, placed in the nanomolar and sub-micromolar range, largely exceeded the activity of cisplatin. Binding to human serum albumin, either HSA (human serum albumin) or HSA(faf) (fatty acid-free human serum albumin) does not affect the complex activity. Fluorescence studies revealed that the present ruthenium complex strongly quench the intrinsic fluorescence of albumin. Cell death by the [Ru(eta(5)-C5H5)(PPh3)(Me(2)bpy)][CF3SO3] complex was reduced in the presence of endocytosis modulators and at low temperature, suggesting an energy-dependent mechanism consistent with endocytosis. On the whole, the biological activity evaluated herein suggests that the complex could be a promising anticancer agent. (C) 2013 Elsevier Inc. All rights reserved.
- DNA interaction and cytotoxicity studies of new ruthenium(II) cyclopentadienyl derivative complexescontaining heteroaromatic ligandsPublication . Moreno, Virtudes; Font-Bardia, Merce; Calvet, Teresa; Julia Lorenzo; Aviles, Francesc Xavier; Garcia, M. Helena; Morais, Tânia S.; Valente, Andreia; Robalo, Maria PaulaFour ruthenium(II) complexes with the formula [Ru(eta(5)-C(5)H(5))(PP)L][CF(3)SO(3)], being (PP = two triphenylphosphine molecules), L = 1-benzylimidazole, 1; (PP = two triphenylphosphine molecules), L = 2,2'bipyridine, 2; (PP = two triphenylphosphine molecules), L = 4-Methylpyridine, 3; (PP = 1,2-bis(diphenylphosphine) ethane), L = 4-Methylpyridine, 4, were prepared, in view to evaluate their potentialities as antitumor agents. The compounds were completely characterized by NMR spectroscopy and their crystal and molecular structures were determined by X-ray diffraction. Electrochemical studies were carried out giving for all the compounds quasi-reversible processes. The images obtained by atomic force microscopy (AFM) suggest interaction with pBR322 plasmid DNA. Measurements of the viscosity of solutions of free DNA and DNA incubated with different concentrations of the compounds confirmed this interaction. The cytotoxicity of compounds 1234 was much higher than that of cisplatin against human leukemia cancer cells (HL-60 cells). IC(50) values for all the compounds are in the range of submicromolar amounts. Apoptotic death percentage was also studied resulting similar than that of cisplatin. (C) 2010 Elsevier Inc. All rights reserved.
- First heterobimetallic Cu(i)-dppf complexes designed for anticancer applications: synthesis, structural characterization and cytotoxicityPublication . Bravo, Catarina; M. Paula Robalo; Marques, Fernanda; Fernandes, Alexandra; Sequeira, Diogo A.; M. Fatima M. Piedade; Garcia, M. Helena; Villa De Brito, Maria José; Morais, TâniaA new family of eight heterobimetallic Cu(i)-dppf complexes of general formula [Cu(dppf)L][BF4] with dppf = 1,1 '-bis(diphenylphosphino)ferrocene and L representing N,N-, N,O- and N,S-heteroaromatic bidentate ligands have been synthesized and fully characterized by classical analytical, spectroscopic and electrochemical methods. The single crystal structures of [Cu(dppf)(pBI)][BF4] (6), [Cu(dppf)(dpytz)][BF4] (7) and [Cu(dppf)(5-Aphen)][BF4] (8) complexes (where pBI = 2-(2-pyridyl)benzimidazole, dpytz = 3-(2-pyridyl)-5,6-diphenyl-1,2,4-triazine and 5-Aphen = 1,10-phenanthrolin-5-amine) were determined by X-ray diffraction studies. Cytotoxicity of all complexes was evaluated in two human breast adenocarcinoma cell lines (MCF7 and MDAMB231). All the complexes exhibit high cytotoxicity against both human breast cancer cells with IC50 values far lower than those found for the antitumor drug cisplatin in the same cell lines. The IC50 values on primary healthy fibroblasts are of the same order of magnitude as those found for the tumoral cells.
- Mono(Eta(5)-cyclopentadienyl)metal(II) complexes with thienyl acetylide chromophores: synthesis, electrochemical studies, and first hyperpolarizabilitiesPublication . Silva, Tiago J. L.; Mendes, Paulo J.; Santos, Ana Margarida; Garcia, M. Helena; Robalo, Maria Paula; Ramalho, J. P. Prates; Carvalho, A. J. Palace; Buechert, Marina; Wittenburg, Christian; Heck, JuergenA series of mono(eta(5)-cyclopentadienyl)metal-(II) complexes with nitro-substituted thienyl acetylide ligands of general formula [M(eta(5)-C5H5)(L)(C C{C4H2S}(n)NO2)] (M = Fe, L = kappa(2)-DPPE, n = 1,2; M = Ru, L = kappa(2)-DPPE, 2 PPh3, n = 1, 2; M = Ni, L = PPh3, n = 1, 2) has been synthesized and fully characterized by NMR, FT-IR, and UV-Vis spectroscopy. The electrochemical behavior of the complexes was explored by cyclic voltammetry. Quadratic hyperpolarizabilities (beta) of the complexes have been determined by hyper-Rayleigh scattering (HRS) measurements at 1500 nm. The effect of donor abilities of different organometallic fragments on the quadratic hyperpolarizabilities was studied and correlated with spectroscopic and electrochemical data. Density functional theory (DFT) and time-dependent DFT (TDDFT) calculations were employed to get a better understanding of the second-order nonlinear optical properties in these complexes. In this series, the complexity of the push pull systems is revealed; even so, several trends in the second-order hyperpolarizability can still be recognized. In particular, the overall data seem to indicate that the existence of other electronic transitions in addition to the main MLCT clearly controls the effectiveness of the organometallic donor ability on the second-order NLO properties of these push pull systems.
- New iron(II) cyclopentadienyl derivative complexes: synthesis and antitumor activity against human leucemia cancer cellsPublication . Valente, Andreia; Santos, Ana Margarida; Côrte-Real, Leonor; Robalo, Maria Paula; Moreno, Virtudes; Font-Bardia, Merce; Calvet, Teresa; Lorenzo, Julia; Garcia, M. HelenaA new family of "Fe-II(eta(5)-C5H5)" half sandwich compounds bearing a N-heteroaromatic ligand coordinated to the iron center by a nitrile functional group has been synthesized and fully characterized by NMR and UV-Vis spectroscopy. X-ray analysis of single crystal was achieved for complexes 1 and 3, which crystallized in the monoclinic P2(1)/c and monoclinic P2(1)/n space groups, respectively. Studies of interaction of these five new complexes with plasmid pBR322 DNA by atomic force microscopy showed very strong and different types of interaction. Antiproliferative tests were examined on human leukemia cancer cells (HL-60) using the MTT assay, and the IC50 values revealed excellent antiproliferative activity compared to cisplatin. (C) 2014 Elsevier B.V. All rights reserved.
- New water-soluble Ruthenium(II) cytotoxic complex: biological activity and celular distributionPublication . Morais, Tânia S.; Santos, Filipa C.; Jorge, Tiago F.; Côrte-Real, Leonor; Madeira, Paulo J. Amorim; Marques, Fernanda; Robalo, Maria Paula; Matos, António; Santos, Isabel; Garcia, M. HelenaA novel water soluble organometallic compound, [RuCp(mTPPMSNa)(2,2'-bipy)][CF3SO3] (TM85, where Cp=eta(5)-cyclopentadienyl, mTPPMS = diphenylphosphane-benzene-3-sulfonate and 2,2'-bipy = 2,2'-bipyridine) is presented herein. Studies of interactions with relevant proteins were performed to understand the behavior and mode of action of this complex in the biological environment. Electrochemical and fluorescence studies showed that TM85 strongly binds to albumin. Studies carried out to study the formation of TM85 which adducts with ubiquitin and cytochrome c were performed by electrospray ionization mass spectrometry (ESI-MS). Antitumor activity was evaluated against a variety of human cancer cell lines, namely A2780, A2780cisR, MCF7, MDAMB231, HT29, PC3 and V79 non-tumorigenic cells and compared with the reference drug cisplatin. TM85 cytotoxic effect was reduced in the presence of endocytosis modulators at low temperatures, suggesting an energy-dependent mechanism consistent with endocytosis. Ultrastructural analysis by transmission electron microscopy (TEM) revealed that TM85 targets the endomembranar system disrupting the Golgi and also affects the mitochondria. Disruption of plasma membrane observed by flow cytometry could lead to cellular damage and cell death. On the whole, the biological activity evaluated herein combined with the water solubility property suggests that complex TM85 could be a promising anticancer agent. (C) 2013 Elsevier Inc. All rights reserved.
- Novel "ruthenium cyclopentadienyl" - peptide conjugate complexes against human FGFR(+) breast cancerPublication . Machado, João Franco; Machuqueiro, Miguel; Marques, Fernanda; Robalo, M. Paula; Piedade, M. Fatima M.; Garcia, M. Helena; Correia, João D. G.; Morais, TâniaIn this work we explored the possibility of improving the selectivity of a cytotoxic Ru complex [RuCp(PPh3)(2,2'-bipy)][CF3SO3] (where Cp = eta(5)-cyclopentadienyl) TM34 towards FGFR(+) breast cancer cells. Molecular dynamics (MD) simulations of TM34 in a phosphatidylcholine membrane model pinpointed the cyclopentadienyl group as a favorable derivatization position for the peptide conjugation approach. Three new Ru(II) complexes presenting a functionalized eta(5)-cyclopentadienyl were synthesized, namely [Ru(eta(5)-C5H4COOH)(2,2'-bipy)(PPh3][CF3SO3] (TM281) and its precursors, [Ru(eta(5)-C5H4COOCH2CH3)(eta(2)-2,2'-bipy)(PPh3)][CF3SO3] (3) and [Ru(eta(5)-C5H4COOCH2CH3)(PPh3)(2)Cl] (2). Complex TM281 was prepared by the hydrolysis of the ethyl ester group appended to the eta(5)-cyclopentadienyl ligand of complex 3 with K2CO3 in water/acetonitrile, followed by mild protonation using an ion exchange resin. The newly synthesized complexes were fully characterized by NMR, FTIR and UV-vis spectroscopic techniques. Also, electrochemical studies were carried out by means of cyclic voltammetry in order to evaluate the stability of the compounds. Single crystal X-ray diffraction studies were carried out for compounds 3 and TM281 which crystallized in the monoclinic system, space group P21/n. The unprecedented synthesis and characterization of three half-sandwich ruthenium(II)-cyclopentadienyl peptide conjugates and their preliminary biological evaluation against human FGFR(+) and FGFR(-) breast cancer cells are also reported.
- Novel ruthenium methylcyclopentadienyl complex bearing a bipyridine perfluorinated ligand shows strong activity towards colorectal cancer cellsPublication . Teixeira, Ricardo G.; Brás, Ana Rita; Côrte-Real, Leonor; Tatikonda, Rajendhraprasad; Sanches, Anabela; Robalo, Maria Paula; Avecilla, Fernando; Moreira, Tiago; Garcia, M. Helena; Haukka, Matti; Preto, Ana; Valente, AndreiaThree new compounds have been synthesized and completely characterized by analytical and spectroscopic techniques. The new bipyridine-perfluorinated ligand L1 and the new organometallic complex [Ru(eta(5)-MeCp)(PPh3)(2)Cl] (Ru1) crystalize in the centrosymmetric triclinic space group P (1) over bar. Analysis of the phenotypic effects induced by both organometallic complexes Ru1 and [Ru(eta(5)-MeCp)(PPh3)(L1)] [CF3SO3] (Ru2), on human colorectal cancer cells (SW480 and RKO) survival, showed that Ru2 has a potent anti-proliferative activity, 4-6 times higher than cisplatin, and induce apoptosis in these cells. Data obtained in a noncancerous cell line derived from normal colon epithelial cells (NCM460) revealed an intrinsic selectivity of Ru2 for malignant cells at low concentrations, showing the high potential of this compound as a selective anticancer agent. (C) 2017 Elsevier Masson SAS. All rights reserved.
- Novel ruthenium methylcyclopentadienyl complex bearing a bipyridine perfluorinated ligand shows strong activity towards colorectal cancer cellsPublication . Gonçalves Teixeira, Ricardo; Brás, Ana Rita; Côrte-Real, Leonor; Tatikonda, Rajendhraprasad; Sanches, Anabela; Robalo, Maria Paula; Avecilla, Fernando; Moreira, Tiago; Garcia, M. Helena; Haukka, Matti; Preto, Ana; Valente, AndreiaThree new compounds have been synthesized and completely characterized by analytical and spectroscopic techniques. The new bipyridine-perfluorinated ligand L1 and the new organometallic complex [Ru(η5-MeCp)(PPh3)2Cl] (Ru1) crystalize in the centrosymmetric triclinic space group P
1¯. Analysis of the phenotypic effects induced by both organometallic complexes Ru1 and [Ru(η5-MeCp)(PPh3)(L1)][CF3SO3] (Ru2), on human colorectal cancer cells (SW480 and RKO) survival, showed that Ru2 has a potent anti-proliferative activity, 4–6 times higher than cisplatin, and induce apoptosis in these cells. Data obtained in a noncancerous cell line derived from normal colon epithelial cells (NCM460) revealed an intrinsic selectivity of Ru2 for malignant cells at low concentrations, showing the high potential of this compound as a selective anticancer agent.