Elisabetta Iengo

Influence of chemical stability on the activity of the antimetastasis ruthenium compound NAMI-A

The influence of chemical stability on the antimetastatic ruthenium(III) compound imidazolium trans-imidazoletetrachlorodimethylsulphoxideruthenium(III) (NAMI-A) in aqueous solution was studied both in vitro and in vivo. The loss of dimethyl-sulphoxide (DMSO) ligand from the compound was tested by using a NAMI-A solution acidified with HCl at pH 3.0 and aged for 0, 4, 8 and 24 h prior to intraperitoneal (i.p.) injection into CBA mice bearing advanced MCa mammary carcinoma. The activity of NAMI-A on lung metastases showed no change even after the loss of DMSO ligand from up to 50% of the molecules. The reduction of NAMI-A did not modify the number of KB cells blocked in the S+G2M phases, independent of whether the reduction occurred outside the cells or after loading the cells with the compound prior to treatment with the reductants (ascorbic acid, glutathione or cysteine). In vivo, the complete reduction of NAMI-A with equivalent amounts of ascorbic acid, glutathione or cysteine prior to administration to mice bearing advanced MCa mammary carcinoma was more active than NAMI-A alone. The data show that NAMI-A, although undergoing a series of chemical modifications, maintains its antimetastatic activity in a broad range of experimental conditions.

Efficient photocatalytic hydrogen generation from water by a cationic cobalt(II) porphyrin

Efficient photocatalytic hydrogen evolution is obtained from 1 M phosphate buffer at pH 7 in the presence of a Ru(bpy)3(2+) sensitizer, an ascorbic acid sacrificial donor, and a water-soluble Co(II) porphyrin catalyst. Spectroscopic investigation of the system by stationary and time-resolved techniques enables a complete characterization of the photoinduced dynamics.

Photocatalytic Hydrogen Evolution with a Self‐Assembling Reductant–Sensitizer–Catalyst System

A noble-metal-free system for photochemical hydrogen production is described, based on ascorbic acid as sacrificial donor, aluminium pyridyl porphyrin as photosensitizer, and cobaloxime as catalyst. Although the aluminium porphyrin platform has docking sites for both the sacrificial donor and the catalyst, the resulting associated species are essentially inactive because of fast unimolecular reversible electron-transfer quenching. Rather, the photochemically active species is the fraction of sensitizer present, in the aqueous/organic solvent used for hydrogen evolution, as free species. As shown by nanosecond laser flash photolysis experiments, its long-lived triplet state reacts bimolecularly with the ascorbate donor, and the reduced sensitizer thus formed, subsequently reacts with the cobaloxime catalyst, thereby triggering the hydrogen evolution process. The performance is good, particularly in terms of turnover frequencies (TOF=10.8 or 3.6 min(-1), relative to the sensitizer or the catalyst, respectively) and the quantum yield (Φ=4.6%, that is, 9.2% of maximum possible value). At high sacrificial donor concentration, the maximum turnover number (TON=352 or 117, relative to the sensitizer or the catalyst, respectively) is eventually limited by hydrogenation of both sensitizer (chlorin formation) and catalyst.

Metal-organic transmembrane nanopores.

A stable tetraporphyrin metallacycle with Re(I) corners (1) is capable of forming nanopores in a liposomial membrane, provided that the porphyrin units are properly functionalized with peripheral carboxylic acid residues that, by establishing an hydrogen bond network, allow the formation of dimers that span the depth of the membrane.

Effects of NAMI-A and some related ruthenium complexes on cell viability after short exposure of tumor cells.

A series of three ruthenium complexes, i.e. trans-dichlorotetrakisdimethyl-sulfoxide ruthenium(II) (trans-Ru), imidazolium trans-imidazoletetra-chlororuthenate (ICR) and sodium trans-tetramethylensulfoxideisoquinoline-tetrachlororuthenate (TEQU), were studied in vitro in comparison to NAMI-A, a potent ruthenium-based antimetastasis agent. In vitro challenge of TS/A adenocarcinoma or KB oral carcinoma tumor cells with 10−4 M concentration for 1 h evidenced the lack of cytotoxicity of NAMI-A, ICR and trans-Ru, the accumulation of cells in the G2/M pre-mitotic cell phase by NAMI-A and the attachment of tumor cells to the plastic substrate was significantly greater for NAMI-A than for ICR. These data stress that in vitro cytotoxicity is not necessary for in vivo activity of ruthenium antitumor complexes: NAMI-A, ICR and trans-Ru, are in fact known to be active against murine tumors in the mouse system. Rather, TEQU, the compound free of in vivo activity, was the only one to reduce cell growth of in vitro cultured cells. In conclusion, the data on the effects of NAMI-A on in vitro cultured cells show that the increase of cell adhesion properties and the transient cell cycle arrest in the G2/M phase are much more relevant than the effects on cell properties relevant to cell growth (i.e. on CD44, CD54 or CD71 antigens) for determining in vivo anti-metastasis activity

Novel mono- and dinuclear ruthenium nitrosyls with coordinated pyrazine

Abstract The synthesis and characterization of some novel mono- and dinuclear ruthenium nitrosyls bearing either terminal ([NBu4][trans-RuCl4(pyz)(NO)] (1a) and [NBu4][cis-RuCl4(pyz)(NO)] (1b)) or bridging pyrazine ([NBu4]2[{trans/cis-RuCl4(NO)}2(μ-pyz)] (trans,trans 2a, cis,cis 2b, trans,cis 2c)) are reported. Compounds 1 and 2 were prepared from the same precursor, [NBu4][trans-RuCl4(dmso-O)(NO)], upon treatment with pyrazine in different ratios. Pure compounds were obtained by crystallization or column chromatography. All species possess the linear {RuII(NO+)}6 moiety, and the NO stretching frequency is quite sensitive to the nature of the trans ligand (either N or Cl). The unbound termini of the pyrazine ligands in compounds 1a and 1b are capable of further reaction with metal centers; treatment of the two isomers with a stoichiometric amount of [Ru(TPP)(CO)(EtOH)] (TPP=tetraphenylporphyrinate) led to the quantitative formation of the unsymmetrical dinuclear species [NBu4][{trans-RuCl4(NO)}(μ-pyz){Ru(TPP)(CO)}] (3a) and [NBu4] [{cis-RuCl4(NO)}(μ-pyz){Ru(TPP)(CO)}] (3b), respectively, in which pyrazine bridges two ruthenium centers in different environments. Thus monomers 1a and 1b can be considered as new examples of complexed bridging ligands that might be used as building blocks in the construction of supramolecular assemblies. The crystal structures of the mononuclear species 1a and 1b, and of the dinuclear species 3a were also determined.

Porphyrin–cobaloxime dyads for photoinduced hydrogen production: investigation of the primary photochemical process

Three porphyrin-cobaloxime dyads, suitable for application in photoinduced hydrogen generation with sacrificial donors, are characterized by ultrafast spectroscopy in order to clarify the primary photochemical events.

Pyridylporphyrins peripherally coordinated to ruthenium-nitrosyls, including the water-soluble Na4[Zn·4′TPyP{RuCl4(NO)}4]: synthesis and structural characterization

Several new ruthenium-nitrosyl conjugates with meso-4′pyridylporphyrins, namely the two anionic isomers [nBu4N][trans-RuCl4(4′MPyP)(NO)] (1) and [nBu4N][cis-RuCl4(4′MPyP)(NO)] (2), the two neutral isomers [mer,trans-RuCl3(4′MPyP)2(NO)] (3) and [mer,cis-RuCl3(4′MPyP)2(NO)] (4), and the tetraruthenated adduct [nBu4N]4[4′TPyP{RuCl4(NO)}4] (5) were obtained by reaction of [nBu4N][trans-RuCl4(dmso-O)(NO)] with 4′MPyP and 4′TPyP (meso-4′monopyridylporphyrin and meso-4′tetrapyridylporphyrin, respectively). The X-ray structures of 2, 4, and 5 are described. Exchange of nBu4N+ for Na+ eventually led to the water-soluble tetraruthenated porphyrin Na4[Zn·4′TPyP{RuCl4(NO)}4] (6·Zn).

New meso-substituted trans-A2B2 di(4-pyridyl)porphyrins as building blocks for metal-mediated self-assembling of 4 + 4 Re(I)–porphyrin metallacycles

The reaction between 5-(4-pyridyl)dipyrrylmethane and aromatic aldehydes affords meso-arylsubstituted trans-A2B2 di(4-pyridyl)porphyrins which are key building blocks in the metal-mediated self-assembling of supramolecular structures. A careful optimization of the reaction conditions allowed us to obtain 5,15-diphenyl-10,20-di(4-pyridyl)porphyrin (P1), and two analogues bearing on the meso-phenyl substituents two dipropyl- (P4) or dihexyl-alkyl chains (P5), with yields ranging from 53 to 63%. Porphyrin P1 reacts with Re(CO5)Br to give the expected 4 + 4 Re(I)-porphyrin metallacycle which has been fully characterized by means of infrared, NMR and UV-Vis (absorption and emission) spectroscopies and by guest inclusion studies. Unexpectedly the addition of alkyl chains to the porphyrin fragment, which increase the solubility of the porphyrin in organic solvents, has the opposite effect on the adduct with Re(I). Indeed, the reaction between Re(CO5)Br and porphyrins P4,5 gives very insoluble materials, hampering their complete characterization.

Zinc Porphyrin–Re(I) Bipyridyl–Fullerene Triad: Synthesis, Characterization, and Kinetics of the Stepwise Electron-Transfer Processes Initiated by Visible Excitation

A new triad system featuring one zinc porphyrin and one fullerene moieties attached to a central redox-active Re(I) connector was obtained in remarkable yield by cleverly exploiting a facile two-step synthesis. Detailed description and discussion on the characterization of this multicomponent system and of its parent free-base analogue are presented, along with a kinetic study of the stepwise electron-transfer processes occurring upon visible excitation.