Ronny R. Ribeiro

Synthesis, characterization and chemoprotective activity of polyoxovanadates against DNA alkylation

The alkylation of pUC19 plasmid DNA has been employed as a model reaction for the first studies on chemoprotective action by a mixed-valence (+IV/+V) polyoxovanadate. A new, non-hydrothermal route for the high yield preparation of the test compound is described. The deep green, microcrystalline solid A was isolated after a three-day reaction in water at 80°C and 1 atm, while the reaction at 100°C gave green crystals of B. Both solids were structurally characterized by X-ray diffractometry and FTIR, EPR, NMR and Raman spectroscopies. Product A was identified as (NH(4))(2)V(3)O(8), while B corresponds to the spherical polyoxoanion [V(15)O(36)(Cl)](6-), isolated as the NMe(4)(+) salt. The lack of solubility of A in water and buffers prevented its use in DNA interaction studies, which were then carried out with B. Complex B was also tested for its ability to react with DNA alkylating agents by incubation with diethylsulphate (DES) and dimethylsulphate (DMS) in both the absence and presence of pUC19. For DMS, the best results were obtained with 10 mM of B (48% protection); with DES, this percentage increased to 70%. The direct reaction of B with increasing amounts of DMS in both buffered (PIPES 50 mM) and non-buffered aqueous solutions revealed the sequential formation of several vanadium(IV), vanadium(V) and mixed-valence aggregates of different nuclearities, whose relevance to the DNA-protecting activity is discussed.

Synthesis, structural characterization and cytotoxic activity of ternary copper(II)–dipeptide–phenanthroline complexes. A step towards the development of new copper compounds for the treatment of cancer

In the search for new compounds with antitumor activity, coordination complexes with different metals are being studied by our group. This work presents the synthesis and characterization of six copper complexes with general stoichiometry [Cu(L-dipeptide)(phen)]·nH2O (were phen=1,10-phenanthroline) and their cytotoxic activities against tumor cell lines. To characterize these systems, analytical and spectroscopic studies were performed in solid state (by UV-visible, IR, X-ray diffraction) including the crystal structure of four new complexes (of the six complexes studied): [Cu(Ala-Phe)(phen)]·4H2O, [Cu(Phe-Ala)(phen)]·4H2O, [Cu(Phe-Val)(phen)]·4.5H2O and [Cu(Phe-Phe)(phen)]·3H2O. In all of them, the copper ion is situated in a distorted squared pyramidal environment. The phen ligand is perpendicular to the dipeptide, therefore exposed and potentially available for interaction with biological molecules. In addition, for all the studied complexes, structural information in solution using EPR and UV-visible spectroscopies were obtained, showing that the coordination observed in solid state is maintained. The lipophilicity, DNA binding and albumin interaction were also studied. Biological experiments showed that all the complexes induce cell death in the cell lines: HeLa (human cervical adenocarcinoma), MCF-7 (human metastatic breast adenocarcinoma) and A549 (human lung epithelial carcinoma). Among the six complexes, [Cu(Ala-Phe)(phen)] presents the lowest IC50 values. Taken together all these data we hypothesize that [Cu(Ala-Phe)(phen)] may be a good candidate for further studies in vivo.

Oxidized few layer graphene and graphite as metal-free catalysts for aqueous sulfide oxidation

Few layer graphene and natural graphite were chemically modified by oxidation with HNO3 at 80 and 140 °C and used to promote the oxidation of sulfide ions in aqueous solutions. TEM, potentiometric titration, XRD, BET and Raman spectroscopy show that HNO3 treatment even at 140 °C did not modify the graphene and graphite morphologies but produced significant amounts of different oxygen surface groups. The presence of these groups on few layer graphene and graphite strongly increased the Saq2− oxidation, showing activities comparable to a high surface area activated carbon with a similar amount of oxygen surface groups. The obtained results suggest that the sulfide oxidation efficiency requires a balance between two important effects, i.e. the presence of oxygen functionalities to initiate the Saq2− oxidation and the electrical conductivity that is important to further transfer the electrons removed from sulfide.

Preparation, crystallography and spectroscopic properties of the polymeric {(1-(E)-2-pyridinylmethylidene)semicarbazone)(aqua)copper(II)} sulphate dihydrate complex: Evidence of dynamic Jahn–Teller effect

Pyridine-2-carbaldehyde semicarbazone ligand (HL) reacts with copper(II) sulphate in water solution to yield the coordination polymer [{Cu(II)(HL)(H(2)O)(SO(4))}(n)] (1). The crystals are triclinic with space group P(-1) and the metal ion is occupying a distorted octahedral geometry. EPR results show that a dynamic Jahn-Teller (J-T) effect is operative in water solutions and also support the stability of the polymeric chains as they continue to show a characteristic half-field Δm(S)=±2 transitions. UV-visible spectrum analysis allowed access to the J-T stabilization energy of 5995 cm(-1) in water. Thermogravimetric/differential thermal analysis curves showed a step-by-step decomposition of complex 1 with loss of water, release of SO(3) and oxidation of the semicarbazone ligand in the 30-422°C range.

Spectroscopic, electrochemical, magnetic and structural investigations of dimanganese-(II/II) and mixed-valence-(II/III)-tetraiminodiphenolate complexes

Synthesis, spectroscopic [electron paramagnetic resonance (EPR), UV-Vis and Fourier transform infrared spectroscopy (FTIR)], magnetic and spectroeletrochemical properties of [MnII2(tidf)(OAc)(ClO4)(MeOH)] (tidf = a Robson type macrocyclic ligand obtained through condensation of 2,6-diformyl-4-methylphenol and 1,3-diaminopropane) are reported. Compound [MnII2(tidf)(OAc)(ClO4)(MeOH)] shows a weak antiferromagnetic behavior with exchange coupling constant J = -1.59(1) cm-1. UV-Vis and EPR spectroelectrochemical response after oxidation of complex [MnII2(tidf)(OAc)(ClO4)(MeOH)] detected the stabilization of mixed-valence Mn2(II/III) species in solution showing spectral features similar to the ones of the isolated mixedvalence [MnIIMnIII(tidf)Br3(H2O)2] compound. Crystallization of [MnII2(tidf)(OAc)(ClO4)(MeOH)] surprisingly produced the trimanganese complex [Mn3III/II/III(tidf)2(µ-OAc)2](ClO4)2, not observed in solution. It contains two pentacoordinated [MnIII(tidf)]+ units, each one connected to a central hexacoordinated MnII ion through one µ-phenolate and one µ-acetate bridge.

Metal complexes of a pentadentate N2O3bis(semicarbazone) Schiff-base. A case study of structure-spectroscopy correlation

Schiff condensation of 2,6-diformyl 4-methylphenol with semicarbazide hydrochloride in 1:2 molar ratio produces the bis(semicarbazone) ligand, herein called H3L. A comprehensive spectroscopic analysis of the compound was performed by (1)H and (13)C NMR, FTIR and electronic spectroscopies. Assignments to the UV-vis spectrum of H3L were supported by semi-empirical quantum mechanics ZINDO/S calculations. The ligand H3L forms monoclinic crystals in the space group P21/c and its structure is stabilized by classic hydrogen bonds with propanone molecules. It promptly reacts with first row metal ions to produce the following coordination compounds: [Co2(L)(μ-NO3)]·DMF, [Ni2(H2L)(μ-CH3COO)(CH3COO)2]·2H2O, [Cu2(L)(μ-NO3)(H2O)2]·H2O, [Cu2(L)(μ-CH3COO)(H2O)2]·H2O and [Cu2(H2L)(μ-Cl)Cl2]·3H2O, that have different compositions, depending on the degree of deprotonation of the ligand upon coordination. Electronic and EPR spectroscopies as well as effective magnetic moment measurements of the complexes were used in an attempt to better understand their mode of coordination, the microsymmetry around the metal ions and magnetic properties.

Chemoprotective activity of mixed valence polyoxovanadates against diethylsulphate in E. coli cultures: insights from solution speciation studies

The mixed valence polyoxovanadates [(CH3)4N]6[V15O36(Cl)] (A) and K(NH4)4[H6V14O38(PO4)]·11H2O (B) were evaluated for their chemoprotective activity against the alkylating agent diethylsulphate (DES) in Escherichia coli DH5α cultures. Compound A was synthesized previously by our and other research groups and product B was prepared in this work by reaction of NH4VO3, mannitol and KH2PO4 (1 : 0.5 : 0.1) in water under reflux at atmospheric pressure. Polyoxovanadate A showed to be non-toxic to E. coli up to the concentration of 10.0 mmol L−1, and its presence in cultures treated with a fixed concentration of DES (6.0 mmol L−1) led to a chemoprotective effect of up to 40% compared to the control cells without A. In contrast, product B exhibited growth inhibitory activity against E. coli with a GI50 value of 8.2 mmol L−1 and was unable to protect the bacteria from the alkylating agent in conditions similar to those employed for A. Speciation studies were carried out for A and B by 51V NMR and EPR spectroscopies in aqueous solution and Luria–Bertani (LB) broth. The results indicate that the polynuclear structure of A is more stable in LB than in pure aqueous solution, and that A is able to react with increasing amounts of DES. Polyoxovanadate B, in turn, suffers rapid breakage and concentration-/pH-dependent rearrangements in both water and LB, forming from simple mononuclear complexes to larger aggregates such as [H4VV14O38(PO4)]5−, [HVV10O28]5− and one or more mixed valence polyoxovanadates. The dominant vanadium(V) species in LB solutions of B, [HV10O28]5−, is poorly reactive towards DES, being also known to inhibit biological processes in living cells; this may relate to the lack of chemoprotection by B and to the actual increase in toxicity observed when E. coli cultures were exposed to both DES and B. Taken together, these results indicate that the observed chemoprotective effect is not only highly dependent on the solution stability of the polyoxometalates, but is also limited by the formation of decomposition products, such as decavanadate and mononuclear VO2+ complexes, which are not able to react with and therefore do not deactivate the alkylating agent in the culture media.

A Rare Example of Four-Coordinate Nonoxido Vanadium(IV) Alkoxide in the Solid State: Structure, Spectroscopy, and Magnetization Dynamics

The distorted tetrahedral [V(OAd)4] alkoxide (OAd = 1-adamantoxide, complex 1) is the first homoleptic, mononuclear vanadium(IV) alkoxide to be characterized in the solid state by X-ray diffraction analysis. The compound crystallizes in the cubic P4̅3 n space group with two highly disordered, crystallographically independent molecules in the asymmetric unit. Spin Hamiltonian parameters extracted from low temperature X- and Q-band electron paramagnetic resonance (EPR) experiments performed for polycrystalline samples of 1, both in the concentrated (bulk) form and diluted in the diamagnetic [Ti(OAd)4] analogue, reveal a fully axial system with g z < g x, g y and A z ≫ A x, A y. Complex 1 has also been characterized by alternate current susceptometry with varying temperature (3-30 K) and static magnetic field (up to 8.5 T), showing field-induced slow relaxation of the magnetization with relaxation times ranging from ca. 3 ms at 3 K to 0.02-0.03 ms at 30 K, in line with relevant results described recently for other potential molecular quantum bits. Pulsed EPR measurements, in turn, disclosed long coherence times of ca. 4 μs at temperatures lower than 40 K, despite the presence of the H-rich ligands. The slow spin relaxation in 1 is the first observed for a tetracoordinate nonoxido vanadium(IV) complex, and results are compared here to those generated by square-pyramidal VIV(O)2+ and trigonal prismatic V4+ with oxygen donor atom sets. Considering that the number of promising d1 complexes investigated in detail for slow magnetization dynamics is still small, the present work contributes to the establishment of possible structural/electronic correlations of interest to the field of quantum information processing.

Investigations on iron leaching from oxides and its relevance for radical generation during Fenton-like catalysis

Crystalline hematite, goethite, and amorphous iron oxide supported on silica were used to investigate the leaching of iron during heterogeneous Fenton catalysis. The effects of relevant variables, comprising pH, radiation incidence, the presence of reductive species (hydroquinone), and hydrogen peroxide concentration, were evaluated using a first-order factorial design experiment. Results revealed a significant influence of pH, hydroquinone concentration, and radiation incidence for hematite and for the amorphous iron oxide, resulting in acidic and reductive leaching. As for goethite, radiation incidence and pH were the most significant variables. Higher concentrations of iron, which were measured during reactions conducted with iron oxide supported on silica, were attributed to its low crystalline structure. Electron paramagnetic resonance analyses proved the reductive environment provided by radiation and by the presence of reductive species is essential to promote the hydroxyl radical generation by the soluble iron species. The findings suggest that different iron oxides present different mechanisms for iron lixiviation and emphasize the importance of assessing the leaching of iron during Fenton-like reactions.

CCDC 794586: Experimental Crystal Structure Determination

Related Article: G.G.Nunes, A.C.Bonatto, C.G.de Albuquerque, A.Barison, R.R.Ribeiro, D.F.Back, A.V.C.Andrade, E.L.de Sa, F.de O.Pedrosa, J.F.Soares, E.M.de Souza|2012|J.Inorg.Biochem.|108|36|doi:10.1016/j.jinorgbio.2011.11.019