Showing papers by "Vieri Fusi published in 2010"

Efficient Fluorescent Sensors Based on 2,5-Diphenyl[1,3,4]oxadiazole: A Case of Specific Response to Zn(II) at Physiological pH

Abstract: The coordination properties and photochemical responses of three fluorescent polyamine macrocycles, 9,12,15,24,25-pentaaza-26-oxatetracyclo[21.2.1.02,7.017,22]hexaicosa-2,4,6,17,19,21,23,251-octaene (L1), 9,12,15,18,27,28-hexaaza-29-oxatetracyclo[24.2.1.02,7.020,25]enneicosa-2,4,6,20,22,24,26,281-octaene (L2), and 9,12,15,18,21,30,31-heptaaza-32-oxatetracyclo[27.2.1.02,7.023,28]diatriconta-2,4,6,23,25,27,29,311-octaene (L3), toward Cu(II), Zn(II), Cd(II), and Pb(II) are reported. Each ligand contains the 2,5-diphenyl[1,3,4]oxadiazole (PPD) moiety inserted in a polyamine macrocycle skeleton. The stability constants were determined by means of potentiometric measurements in aqueous solution. L1 forms mononuclear complexes only with Cu(II). L2 and L3 form stable mononuclear species with all of the metals, while L3 is able to form dinuclear Cu(II) species. The fluorescence of all ligands was totally quenched by the presence of Cu(II). L2 behaves as an OFF−ON sensor for Zn(II) under physiological conditions, e...

Malten, a new synthetic molecule showing in vitro antiproliferative activity against tumour cells and induction of complex DNA structural alterations

Abstract: BACKGROUND: Hydroxypyrones represent several classes of molecules known for their high synthetic versatility. This family of molecules shows several interesting pharmaceutical activities and is considered as a promising source of new antineoplastic compounds. METHODS: In the quest to identify new potential anticancer agents, a new maltol (3-hydroxy-2-methyl-4-pyrone)-derived molecule, named malten (N,N'-bis((3-hydroxy-4-pyron-2-yl)methyl)-N,N'-dimethylethylendiamine), has been synthesised and analysed at both biological and molecular levels for its antiproliferative activity in eight tumour cell lines. RESULTS: Malten exposure led to a dose-dependent reduction in cell survival in all the neoplastic models studied. Sublethal concentrations of malten induce profound cell cycle changes, particularly affecting the S and/or G2-M phases, whereas exposure to lethal doses causes the induction of programmed cell death. The molecular response to malten was also investigated in JURKAT and U937 cells. It showed the modulation of genes having key roles in cell cycle progression and apoptosis. Finally, as part of the effort to clarify the action mechanism, we showed that malten is able to impair DNA electrophoretic mobility and drastically reduce both PCR amplificability and fragmentation susceptibility of DNA. CONCLUSION: Taken together, these results show that malten may exert its antiproliferative activity through the induction of complex DNA structural modifications. This evidence, together with the high synthetic versatility of maltol-derived compounds, makes malten an interesting molecular scaffold for the future design of new potential anticancer agents.

New family of polyamine macrocycles containing 2,5-diphenyl[1,3,4]oxadiazole as a signaling unit. Synthesis, acid-base and spectrophotometric properties.

Abstract: Synthesis and acid–base properties for three fluorescent polyamine macrocycles 9,12,15,24,25-pentaaza-26-oxatetracyclo[21.2.1.02,7.017,22]hexaicosa-2,4,6,17,19,21,23,251-octaene (L1), 9,12,15,18,27,28-hexaaza-29-oxatetracyclo[24.2.1.02,7.020,25]enneicosa-2,4,6,20,22,24,26,281-octaene (L2) and 9,12,15,18,21,30,31-heptaaza-32-oxatetracyclo[27.2.1.02,7.023,28]diatriconta-2,4,6,23,25,27,29,311-octaene (L3) are reported. Each ligand contains the 2,5-diphenyl[1,3,4]oxadiazole (PPD) unit incorporated in the polyamine macrocycle. The protonation constants of L1–L3 were determined by means of potentiometric measurements in 0.15 mol dm−3 NaCl aqueous solution at 298.1 K. All the ligands are highly fluorescent in aqueous solution under acidic conditions (pH 8, a total quenching of fluorescence is observable in all the ligands. The fluorescence is given by the PPD unit, while the behavior as a function of pH can be rationalized on the basis of photoinduced intramolecular electron transfer (PET) from the HOMO of the donor macrocycle nitrogen atoms to the excited fluorophore unit. The insertion of PPD in a polyamine skeleton strongly improves the fluorescence quantum yield of this class of ligands with respect to those already known.

Synthesis, binding and fluorescence studies of a new neutral H-bonding receptor for anions based on 3,5-bis(trifluoromethyl)phenylurea

Abstract: The synthesis and anion binding studies of the new neutral receptor 1,1′-(2,2′-(4,10-dimethyl-1,4,7,10-tetraazacyclododecane-1,7-diyl)bis(2-oxoethane-2,1-diyl))bis(3-(3,5-bis(trifluoromethyl)phenyl)urea) (L1) are reported. L1 is a macrocyclic ligand containing the 3,5-trifluoromethylphenylureido-binding fragment attached as a side arm on the tetraazacyclododecane. L1 is soluble in numerous organic solvents; the binding properties of L1 towards several simple anions (G) were investigated by NMR, UV–vis and fluorescence techniques in DMSO and CH3CN solutions. L1 is able to bind F− , Cl− and AcO− in both solvents; in addition, it binds Br− in CH3CN. Fluoride shows the highest constant values in the halide series (F− > Cl− > Br− ) and AcO− is the most strongly bound among all the anions investigated. L1 is able to signal the presence of the anions in solution by fluorescence change; in the case of acetate, this occurs in the visible range.

Synthesis, Crystal Structure and Ligational Properties of a New Macrotricyclic Ligand.

Abstract: The synthesis and characterization of the new macrotricycle 10,22,28,32-tetraoxa-1,4,7,13,16,18-hexaazatricyclo[17.5.5.57,13]tetratriacontane L is reported. Its basicity in aqueous solution has been investigated by potentiometric and spectroscopic (1H, 13C NMR) techniques. The basicity constants have been determined (25 °C, I= 0.15 mol dm–3) in two ionic media. Macrotricycle L behaves as a hexaprotic base: log K1= 10.27(3), log K2= 9.52(3), log K3= 7.12(3), log K4= 4.62(3), log K5= 2.80(3), log K6= 2.27(3) in NaClO4 and log K1= 10.09(3), log K2= 9.27(3), log K3= 6.54(3), log K4= 4.88(3), log K5= 3.75(3), log K6= 3.07(3) in NaCl. The constants relative to the equilibrium Cl–+ HnLn+⇌ HnLCl(n–1)+ have been measured: n= 5, log K= 2.48(3); n= 6, log K= 3.59(3). The crystal structure of L has been determined by single-crystal X-ray analysis. The compound crystallizes in a triclinic unit cell (space group P, Z= 2) with lattice constants a= 8.984(5), b= 12.122(2), c= 14.667(3)A, α= 109.52(2), β= 105.47(3), γ= 95.24(3)°. Least-squares refinement converged at R= 0.088 (R′= 0.075) for 3198 unique reflections with I > 4σ(I). The structure shows that the molecule has a skewed cylindrical shape, the bases being formed by the two N2O2 macrocycles with the N(CH2CH2)2 chains constituting the walls. The cylindrane L binds two Li+ ions and the resulting complex has been studied by 7Li NMR spectroscopy. Copper(II) and cadmium(II) complexes with L have been investigated in aqueous solution and their stability constants determined by potentiometric techniques. For both metals the following species have been found: [ML]2+, [MLH]3+, [ML(OH)]+ and [ML(OH)2].