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ABSTRACT: AbstractThe interactions of Cu(II), Zn(II), and Al(III) with 1,6-dimethyl-4-hydroxy-3-pyridinecarboxylic acid (DQ716) and 2,6-dimethyl-3-hydroxy-4-pyridinecarboxylic
acid (DT726), possible chelating agents in Alzheimer’s disease, were investigated in aqueous solution. The proton dissociation
constants of the ligands, the stability constants, and the coordination modes of the metal complexes formed were determined
by pH-potentiometric, UV–vis spectrophotometric, and 1H NMR methods. The nitrogen of the pyridine ring changes the proton affinity of the carboxylate and phenolate moieties and
these pyridine derivatives form stronger complexes with Cu(II), Zn(II), and Al(III) than salicylic acid. Interactions of the
ligands with human serum albumin as their potential transporter in blood were investigated at physiological pH through ultrafiltration
by UV–vis and fluorescence spectroscopy.
Graphical abstract
KeywordsPotentiometry–Carboxylate ligands–Ultrafiltration–Fluorescence spectroscopy–Chelation therapy–Human serum albumin
Monatshefte fuer Chemie/Chemical Monthly 04/2012; 142(4):399-410. · 1.53 Impact Factor
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Davide Barreca,
Giorgio Carraro,
Anjana Devi,
Ettore Fois,
Alberto Gasparotto,
Roberta Seraglia,
Chiara Maccato,
Cinzia Sada,
Gloria Tabacchi,
Eugenio Tondello, Alfonso Venzo,
Manuela Winter
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ABSTRACT: Iron oxide is a key multi-functional material in many different fields of modern technology. The β-Fe(2)O(3) cubic phase, one of the least studied Fe-O systems, was obtained by Chemical Vapor Deposition (CVD) using for the first time a Fe(II) β-diketonate diamine complex, Fe(hfa)(2)·TMEDA, as the molecular source (hfa = 1,1,1,5,5,5-hexafluoro-2,4-pentanedionate; TMEDA = N,N,N',N'-tetramethylethylenediamine). The strong visible light absorption of β-Fe(2)O(3) deposits highlights their possible functional application in photocatalytic hydrogen production under solar light. A comprehensive investigation on the Fe(ii) complex, performed by a joint experimental-theoretical approach, explains the molecular origin of its excellent thermal behaviour and reveals why this species is a successful precursor for the CVD of iron oxide nanostructures.
Dalton Transactions 11/2011; 41(1):149-55. · 3.84 Impact Factor
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ABSTRACT: Four platinum(II) complexes of general formula [PtCl(η(1)-C(9)H(7))L(2)] [where L(2) is 1,2-bis(diphenylphosphino)ethane (dppe) 1 or cycloocta-1,5-diene (cod) 3] and [PtCl(2)L(2)] (where L(2) is dppe 2 or cod 4) were studied. Inhibition growth assays on human tumor cell lines evidenced for 1 and 3 an antiproliferative effect and, interestingly, the cytotoxic effect exerted by 1 is similar to that of cisplatin. Electrochemical and NMR measurements allowed us to determine the structural and redox properties. Investigation of the mechanism of action responsible for the cytotoxicity demonstrated a weak capacity of interacting with DNA. Some experiments performed on rat liver mitochondria indicate that 1 acts as an inducer of the mitochondrial permeability transition, thus leading to the release of proapoptotic factors, such as cytochrome c and apoptosis-inducing factor.
European Journal of Biochemistry 06/2011; 16(5):695-713. · 3.42 Impact Factor
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ABSTRACT: Three different zirconium thio and oxothio clusters, characterized by different coordination modes of dithioacetate and/or monothioacetate ligands, were obtained by the reaction of monothioacetic acid with zirconium n-butoxide, Zr(O(n)Bu)(4), in different experimental conditions. In particular, we isolated the three polynuclear Zr(3)(μ(3)-SSSCCH(3))(2)(SSCCH(3))(6)·2(n)BuOH (Zr(3)), Zr(4)(μ(3)-O)(2)(μ-η(1)-SOCCH(3))(2)(SOCCH(3))(8)(O(n)Bu)(2) (Zr(4)), and Zr(6)(μ(3)-O)(5)(μ-SOCCH(3))(2)(μ-OOCCH(3))(SOCCH(3))(11)((n)BuOH) (Zr(6)) derivatives, presenting some peculiar characteristics. Zr(6) has an unusual star-shaped structure. Only sulfur-based ligands, viz., chelating dithioacetate monoanions and an unusual ethane-1,1,1-trithiolate group μ(3) coordinating the Zr ions, were observed in the case of Zr(3). 1D and 2D NMR analyses confirmed the presence of differently coordinated ligands. Raman spectroscopy was further used to characterize the new polynuclear complexes. Time-resolved extended X-ray absorption fine structure measurements, devoted to unraveling the cluster formation mechanisms, evidenced a fast coordination of sulfur ligands and subsequent relatively rapid rearrangements.
Inorganic Chemistry 12/2010; · 4.60 Impact Factor
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Cristina Marzano,
Silvia Mazzega Sbovata,
Valentina Gandin,
Davide Colavito,
Elda Del Giudice,
Rino A Michelin, Alfonso Venzo,
Roberta Seraglia,
Franco Benetollo,
Mariano Schiavon,
Roberta Bertani
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ABSTRACT: The reactions of cyclopropylamine, cyclopentylamine, and cyclohexylamine with trans-[PtCl2(NCMe)2] afforded the bis-cationic complexes trans-[Pt(amine)2(Z-amidine)2]2+[Cl-]2, 1-3. The solution behavior and biological activity have been studied in different solvents (DMSO, water, polyethylene glycol (PEG 400), and polyethylene glycol dimethyl ether (PEG-DME 500)). The biological activity was strongly influenced by the cycloaliphatic amine ring size, with trans-[Pt(NH2CH(CH2)4CH2)2{N(H) horizontal lineC(CH3)N(H)CH(CH2)4CH2}2]2+[Cl-]2 (3) being the most active compound. Complex 3 overcame both cisplatin and MDR resistance, inducing cancer cell death through p53-mediated apoptosis. Alkaline single-cell gel electrophoresis experiments indicated direct DNA damage, reasonably attributable to DNA adducts of trans-[PtCl(amine)(Z-amidine)2][Cl] species, which can evolve to produce disruptive and nonrepairable lesions on DNA, thus leading to the drug-induced programmed cancer cell death. Preliminary in vivo antitumor studies on C57BL mice bearing Lewis lung carcinoma highlighted that complex 3 promoted a significant and dose-dependent tumor growth inhibition without adverse side effects.
Journal of Medicinal Chemistry 08/2010; 53(16):6210-27. · 4.80 Impact Factor
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ABSTRACT: Deprotonation of 1-methylcytosine (1-MeCy) and 9-methyladenine (9-MeAd) promoted by cis-[L(2)Pt(mu-OH)](2)(NO(3))(2) (L = PPh(3), PMePh(2), (1)/(2)dppe) in PhCN causes the irreversible insertion of a nitrile molecule into the Pt-N4 and Pt-N6 bonds of the cytosinate and adeninate ligands, respectively, to form the stable azametallacycle complexes cis-[L(2)PtNH=C(Ph){1-MeCy(-2H)}]NO(3) (L = PPh(3), 1; PMePh(2), 2; (1)/(2)dppe, 3) and cis-[L(2)PtNH=C(Ph){9-MeAd(-2H)}]NO(3) (L = PPh(3), 4; PMePh(2), 5) containing the deprotonated form of the molecules (Z)-9-N-(1-methyl-2-oxo-2,3-dihydropyrimidin-4(1H)-ylidene)benzimidamide and (Z)-N-(9-methyl-1H-purin-6(9H)-ylidene)benzimidamide. Single-crystal X-ray analyses of 2 and 4 show the metal coordinated to the N3 cytosine site [Pt-N3 = 2.112(7) A] and to the N1 site of adenine [Pt-N1 = 2.116(6) A] and to the nitrogen atom of the inserted benzonitrile [Pt-N2 = 2.043(6) and 2.010(6) A in 2 and 4, respectively], with the exocyclic nucleobase amino nitrogen bound to the carbon atom of the CN group. Complex 2, in solution, undergoes a dynamic process related to a partially restricted rotation around Pt-P bonds, arising from a steric interaction of the oxygen atom of the cytosine with one ring of the phosphine ligands. The reaction of 4 with acetylacetone (Hacac) causes the quantitative protonation of the anionic ligand, affording the acetylacetonate complex cis-[(PPh(3))(2)Pt(acac)]NO(3) and the free benzimidamide NH=C(Ph){9-MeAd(-H)}. In the same experimental conditions, complex 3 reacts with Hacac only partially.
Inorganic Chemistry 02/2010; 49(5):2103-10. · 4.60 Impact Factor
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CrystEngComm 01/2010; 12(4). · 3.84 Impact Factor
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Berichte der deutschen chemischen Gesellschaft 10/2009; 2009(35):5346 - 5351. · 2.94 Impact Factor
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ABSTRACT: A series of new platinum(II) amidine derivatives of the type cis-[PtCl(2){Z-NHC(NHR)Me}(2)] (R=cyclopropyl, 1; cyclopentyl, 2; cyclohexyl, 3) were prepared in high yield by addition of the corresponding cyclic aliphatic amine RNH(2) to the coordinated acetonitrile ligands in cis-[PtCl(2)(NCMe)(2)]. The solution behaviour of 1-3 has been studied in DMSO, PEG 400 (polyethylene glycol) and PEG-DME 500 (polyethylene glycol dimethylether). The amidine complexes 1-3 were evaluated for their cytotoxic properties against a panel of human tumor cell lines containing examples of cervix (HeLa), breast (MCF7), lung (A549) and colon (HCT-15) cancer. Moreover, the amidine complexes were tested for their cytotoxicity against normal human fibroblasts (HFF-1). For comparison purposes, the cytotoxicity of cisplatin was examined under the same experimental conditions. The results obtained showed that PEG and PEG-DME behave as good solvents to carry out biological assays with platinum complexes which are water-insoluble and unstable in DMSO. Complexes 2 and 3 exhibited a biological activity comparable to that of cisplatin.
Journal of inorganic biochemistry 06/2009; 103(8):1113-9. · 3.25 Impact Factor
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ABSTRACT: 1,6-Dimethyl-4-hydroxy-3-pyridinecarboxylic acid (DQ716) and 4-hydroxy-2-methyl-3-pyridinecarboxylic acid (DQ2) were evaluated for possible application to iron (Fe) and aluminium (Al) chelation therapy. Metal/ligand solution chemistry, electrochemistry, cytotoxicity, octanol/water partitioning (D(o/w)), and chelation efficiency, were studied. The Fe(iii)/DQ716, Fe(iii)/DQ2, Al(iii)/DQ716, and Al(iii)/DQ2 solution chemistry was investigated in aqueous 0.6 mol kg(-1) (Na)Cl at 25 degrees C by means of potentiometric titrations, UV-vis spectrophotometry, and (1)H-NMR spectroscopy. DQ716 exhibited the highest coordination efficiency towards Fe(iii) and Al(iii) among all hydroxypyridinecarboxylic acids examined so far, whereas DQ2 complexes were significantly less stable. These results were confirmed by chelation efficiency measurements performed in an octanol-aqueous solution in the presence of those ligands and metals. Partitioning experiments at pH 7.4 showed both DQ716 and DQ2, and their Fe(iii) and Al(iii) complexes, to be hydrophilic. According to the voltammetric data, the free ligands (DQ716 and DQ2) and their metal complexes are not predicted to undergo redox cycling at in vivo conditions. The standard reduction potentials of these complexes, and the kinetics of their formation and dissociation, were obtained. The toxicity of DQ716 and of DQ2 was investigated with human cancer cell lines and normal human fibroblasts. Cytotoxic effects were observed only for DQ2 at 0.1 mM, following 3 d exposure. According to our results, DQ716 has the required favourable properties to be a chelating agent for Fe and Al.
Dalton Transactions 04/2009; · 3.84 Impact Factor
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Dalton Transactions - DALTON TRANS. 01/2009;
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ABSTRACT: In view of a possible application to Fe and Al chelation therapy, 2-methyl-3-hydroxy-4-pyridinecarboxylic acid (DT2) was synthesised, and its complex formation, electrochemical and cytotoxic properties were studied. The complexing properties of DT2 towards Fe(III) and Al(III) were investigated in aqueous 0.6 m (Na)Cl at 25 degrees C by means of potentiometric titrations, UV-vis spectrophotometry, and 1H NMR spectroscopy. DT2 is a triprotic acid (H3L+) having pKa1 = 0.47, pKa2 = 5.64 and pKa3 = 11.18. The metal-ligand complexes observed in solution and their corresponding stability constants (log beta values) are the following: FeLH (19.38), FeL (16.01), FeLH(-1) (12.28), FeL2H2 (37.29), FeL3H3 (53.41), FeL3H2 (47.99), FeL3H (41.21) and FeL3 (34.1); AlLH (17.43), AlL2H2 (33.74), AlL2H (27.6), AlL3H3 (48.72), AlL3H2 (42.67), AlL3H (35.8) and AlL3 (27.92). The complex formation between DT2 and Fe(II) was studied by UV-vis: the weak complex FeLH (log beta = 15.8) was detected. DT2 shows a lower complexation efficiency with Fe(III) and Al(III) than that of other available chelators, but higher than that of its non-methylated analogue 3-hydroxy-4-pyridinecarboxylic acid (DT0). The electrochemical behaviour of DT2 was investigated by means of cyclic voltammetry, indicating that the oxidation of the ligand proceeds through a two electron process with a CECE mechanism. Voltammetric curves suggest that the oxidation or the reduction of DT2 in vivo is unlikely. According to the thermodynamic data, also the Fe(III)-DT2 complexes do not undergo redox cycling at physiological pH. Amperometric titrations of solutions containing Fe(III) and DT2 at pH = 5 indicated the same Fe(III) : ligand stoichiometric ratio as calculated from potentiometric data. The toxicity of DT2 and of other simple hydroxypyridinecarboxylic acids was investigated in vitro and no cytotoxic activity was observed (IC50 > 0.1 mM) on cancer cell lines and also on primary human cells, following a three day exposure.
Dalton Transactions 04/2008; · 3.84 Impact Factor
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ABSTRACT: New benzyliminoether derivatives [PtCl2{N(H)=C(OMe)CH2Ph}2] of cis (1a, 1b) and trans (2a, 2b) geometry were prepared and characterized by means of elemental analysis, multinuclear NMR and FT-IR techniques, and X-ray crystallography; this latter was carried out for 1b. The cytotoxic properties of these new platinum(II) complexes were evaluated in terms of cell growth inhibition against a panel of different types of human cancer cell lines. cis-[PtCl2{E-N(H)=C(OMe)CH2Ph}2] (1a) was significantly more potent than cisplatin against all tumor cell lines tested, showing IC50 values from about 2- to 17-fold lower than the reference compound. Chemosensitivity tests performed on cisplatin-sensitive and -resistant cell lines have demonstrated that complex 1a is able to overcome cisplatin resistance. Analyzing the mechanism by which complex 1a led to cell death, we have found that it induced apoptosis in a dose-dependent manner, accompanied by the activation of caspase-3. The in vivo studies carried out using two transplantable tumor models (L1210 leukemia and Lewis lung carcinoma) showed that derivative 1a induced a remarkable antitumor activity in both tumor models, as measured by prolonged survival and reduced tumor mass compared to control groups.
Journal of Medicinal Chemistry 10/2007; 50(19):4775-84. · 5.25 Impact Factor
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ABSTRACT: Two different methacrylate modified barium-titanium and barium-based oxoclusters, Ba2Ti10(mu3-O)8(mu2-OH)5(mu2-OMc)20(OiPrOMe)2 (1) and [Ba(OMc)2(McOH)3]n (2), were synthesized by reacting methacrylic acid with barium-titanium and barium-zirconium double alkoxides, respectively. The X-ray structure determination of oxocluster 1 shows a core consisting of a ring of 10 titania octahedra, sharing corners, that surround the two barium oxygen decaeders which are linked by common edges to the titania octahedra and the neighboring barium decaeder. The solid-state structure of 2 consists of zigzag chains of edge-sharing {BaO9} polyhedra linked through bridging bidentate metacrylate anions, displaying different coordination mode of carboxylate groups. The presence of methacrylate groups surrounding the two polynuclear compounds has been exploited for the embedding of the oxocluster in inorganic-organic hybrid materials, and some preliminary results are presented.
Inorganic Chemistry 04/2007; 46(9):3459-66. · 4.60 Impact Factor
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ABSTRACT: The Phormidium sp. ETS-05 thermophile blue-green alga is one of the most typical and widespread species of cyanobacteria of the thermal muds of the Euganean hot springs, the therapeutic properties of which have been known since ancient times. The polar diacylglycerolipids of this cyanobacterium consists of monogalactosyldiacylglycerol, digalactosyldiacylglycerol, sulfoquinovosyldiacylglycerol and phosphatidylglycerol. We have isolated and purified these four diacylglycerolipids from ETS-05, and then analysed them for their quantitative and structural features and fatty acid contents. The monogalactosyldiacylglycerol and digalactosyldiacylglycerol show a marked presence of polyunsaturated fatty acids, of which C18 : 4 is the most common. We propose that these glycoglycerolipids can be used as markers for monitoring the thermal mud colonisation process.
Natural Product Research 08/2006; 20(8):766-74. · 1.01 Impact Factor
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Berichte der deutschen chemischen Gesellschaft 01/2006; 2006(6):1284 - 1293. · 2.94 Impact Factor
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ABSTRACT: The thermophilic blue-green alga ETS-05 colonises the therapeutic thermal muds of Abano and Montegrotto, Italy. Following the isolation, purification and identification of monogalactosyldiacylglycerol (MGDG), digalactosyldiacylglycerol (DGDG), sulphoquinovosyldiacylglycerol (SQDG) and phosphatidylglycerol from ETS-05, we here examine their in vivo anti-inflammatory activities. MGDG, DGDG and SQDG inhibit croton-oil-induced ear oedema in the mouse in a dose-dependent manner. Inhibition by MGDG is greater than that of the reference drug, betamethasone 17,21-dipropionate, and is largely abrogated following acyl group saturation. SQDG is the least potent of these glycoglycerolipids, and shows an early transient effect. In the in vivo carrageenan-induced paw oedema model in the mouse, the inhibitory effects are again dose dependent, with an enhanced efficacy of MGDG over DGDG, SQDG and the reference drug, indomethacin. These compounds are all less toxic than indomethacin. The selective and enhanced inhibitory effects of MGDG over DGDG indicate the mechanisms behind these in vivo anti-inflammatory actions.
European Journal of Pharmacology 12/2005; 524(1-3):159-68. · 2.52 Impact Factor
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Applied Organometallic Chemistry 07/2005; 19(9):1002 - 1009. · 2.06 Impact Factor
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Applied Organometallic Chemistry 01/2005; 19(1):59 - 67. · 2.06 Impact Factor
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ABSTRACT: The Al(III)-binding abilities of two aldaric acids, D-saccharic acid and mucic acid (the neutral form is denoted as H(2)L), were studied in solution by means of pH potentiometric, (1)H and (13)C NMR, and ESI-MS techniques. The most probable conformations and isomeric binding modes of the complexes formed in solution were determined by density functional theory (DFT) calculations. A solid D-saccharic acid complex K(2)[[Al(LH(-2))(H(2)O)](2)].H(2)O was isolated and crystallographically characterised. The two alcoholic hydroxy groups alpha to the terminal COO(-) groups were found to take part in the coordination, but in different ways. One of them coordinates in a bridging mode. Detailed ESI-MS and NMR studies proved that the complex retains its structure in solution. However, depending on the ligand and the pH, such complexes may exist in two isomeric forms. DFT calculations on the ion [[Al(LH(-2))(H(2)O)](2)](2-) revealed that several orbitals participate in stabilizing the dimeric arrangement.
Chemistry 04/2004; 10(5):1281-90. · 5.93 Impact Factor
