Lena Ruiz-Ramirez

Schiff-base compartmental macrocyclic complexes

The synthesis of a range of new compartmental macrocyclic complexes based on 2,6-diformyl and -diketo phenol groups is described. The metal-free ligands have been prepared and structurally characterised for the first time, and this has led to the synthesis of novel cubane and platinum-group metal complexes. The synthesis of related dithiophenolato-bridged compartmental complexes of NiII, CuII and ZnII has been achieved and the relevance of these species to metalloproteins is discussed.

Toxic effects of copper-based antineoplastic drugs (Casiopeinas®) on mitochondrial functions

To elucidate some of the subcellular and biochemical mechanisms of toxicity of metal-based antineoplastic drugs, mitochondria and cells were exposed to Casiopeinas), a new class of copper-based compounds with high antineoplastic activity. The rates of respiration and swelling, the H(+) gradient, and the activities of succinate (SDH) and 2-oxoglutarate dehydrogenases (2-OGDH) and ATPase were measured in mitochondria isolated from rat liver, kidney, heart, and hepatoma AS-30D. Also, oligomycin-sensitive respiration and ATP content in hepatoma AS-30D cells were determined. Casiopeinas) (CS) II-gly and III-i inhibited the rates of state 3 and uncoupled respiration in mitochondria. CS II was 10 times more potent than CS III. The sensitivity to CS II was 4-5-fold higher in mitochondria incubated with 2-OG than with succinate. Thus, at low concentrations (< or =10 nmol (mg protein)(-1); 10 microM), CS II disturbed mitochondrial functions only when 2-OG was present, due to a specific inhibition of 2-OGDH. At high concentrations (> or =15nmol (mg protein)(-1)), CS II-induced stimulation of basal respiration, followed by a strong inhibition, which correlated with K(+)-dependent swelling and cytochrome c release, respectively; K(+)-channel openers induce a similar mitochondrial response. Mitochondria from liver, kidney and hepatoma showed a similar sensitivity towards CS II, whereas heart mitochondria were more resistant. Oxidative phosphorylation and ATP content were also decreased in tumor cells by CS II. The data suggested that CS affected several different mitochondrial sites, bringing about inhibition of respiration and ATP synthesis, which could compromise energy-dependent processes such as cellular duplication.

Knigth's Move in the Periodic Table, From Copper to Platinum, Novel Antitumor Mixed Chelate Copper Compounds, Casiopeinas, Evaluated by an in Vitro Human and Murine Cancer Cell Line Panel.

We synthesized a novel anticancer agents based on mixed chelate copper (II) complexes, named Casiopeínas® has of general formula [Cu(N-N)(N-O)H2O]NO3 (where, N-N = diimines as 1,10- phenanthroline, 2,2-bipyridine, or substituted and N-O=aminoeidate or [Cu(N-N)(O-O)H2O]NO3 (where NN= diimines as 10-phenanthroline, 2,2-bipyridine or substituted Casiopeínas I, II, IV, V, VI, VII VIII and O-O=acetylacetonate, salicylaldehidate Casiopínas III). We evaluated the in vitro antitumor activity using a human cancer cell panel and some nurine cancer cells. Eleven Casiopeinas are evaluated in order to acquire some structure-activity correlations and some monodentated Casiopeinäs analogues; cisplatinum was used as control drug. The 50% growth inhibition observed is, in all cases reach with concentrations of Casiopeinas 10 or 100 times lower than cisplatinum. In a previous work we reported the induction of apoptosis by Casiopeina II. The results indicate that Casiopeinass are a promising new anticancer drug candidates to be developed further toward clinical trials.

Synthesis and structure of tetranuclear zinc(II) and binuclear copper(II) complexes of a dithiolate compartmental macrocyclic ligand: a model for the binuclear CuA site in cytochrome c oxidase and N2O reductase

The tetranuclear cluster [Zn2L(µ-OH)]2[ClO4]2·2H2O (L = dianion of the condensation product of 1,3-diaminopropane and 2,6-diformyl-4-methylthiophenol) shows two unique dinuclear ZnII units linked by two µ-hydroxy bridges; the structure of the CuII complex [Cu2L(HOMe)2](NO3)]PF6 shows square-pyramidal coordination at the Cu centres with two thiolate bridges and two terminal N-donors, with a Cu⋯Cu separation of 3.264(2)A.

CU-O STRETCHING FREQUENCY CORRELATION WITH PHENANTHROLINE PKA VALUES IN MIXED COPPER COMPLEXES

Abstract A study of Cu–O vibration frequencies in 32 isostructural mixed copper complexes containing eight differently substituted phenanthrolines and four different oxygen donor bidentate ligands, is presented. In all cases linear correlation was found between phenanthroline p K a values and the studied vibration frequencies, suggesting that an increase in phenanthroline basicity weakens Cu–O bonds in this type of compound.

Kinetics and mechanism of ester hydrolysis by metal complexes of 2,6-diacetylpyridine dioxime

Abstract The rate constants of the cleavage of 4-nitrophenyl acetate by the 2,6-diacetylpyridine dioxime (H2dapd) in pH interval 6-8 increase 103–104 times in the presence of Pb(II), Mn(II) and Cd(II), and 2–100 times in the presence of Ni(II), Hg(II), Pr(III) and Zn(II). Complexation of the oxime ligand with Co(II) and Cu(II) does not affect the reaction rate. The complex with Cd(II) operates in a catalytic regime with respect of the oxime ligand. Spectrophotometric study of the coordination of Cd(II) and Zn(II) with H2dapd reveals formation of M(H2dapd)2+, M(Hdapd)+ and M2(Hdapd)22+ complexes. Formation constants of these complexes as well as acid dissociation constants of free and complexed H2dapd were calculated from spectrophotometric titration results. The reactive species are monomeric complexes of the type M(Hdapd)+ whereas the dimers are unreactive. The reactivity of M(Hdapd)+ complexes correlates with basicity of the coordinated oximate anion. The complexes of Cd(II), Mn(II) and Pb(II) unexpectedly possess higher reactivity than much more basic free oximate anion probably because of stabilisation of carbonyl oxygen by chelation with metal cation in the transition state.

Mercaptoethanesulfonic acid studies with nickel(II) complexes of tetra- and hexadentate ligands containing pyridyl groups: synthesis, structure, spectra and redox behavior

Abstract Nickel(II)complexes of N,N,N′N′-tetrakis(2-pyridylmethyl)ethylenediamine (L1), N,N,N′N′-tetrakis(2-pyridylmethyl)-1,2-diaminopropane (L2), N,N,N′N′-tetrakis(2-pyridylmethyl)-1,3-diaminopropane (L3), N,N′-bis(2-pyridylmethyl)ethylenediamine (L4), N,N′-bis(2-pyridylmethyl)-1,2-diaminopropane (L5) and N,N′-bis(2-pyridylmethyl)-1,3-diaminopropane (L6) were prepared and their spectroscopic and redox behaviors studied. The distorted octahedral geometry was determined for [NiL2](ClO4)2 by using X-ray crystallography. The electronic spectral bands (3A2g→3T2g and 3A2g→1Eg transitions) of NiN6 and NiN4O2 were analyzed; it shows that the former complexes possess well-resolved bands compared to the latter compounds. In addition, the ligand field parameter Dq found for NiN4O2 complexes was much lower than that of NiN6 compounds; thereby, a more positive redox potential was detected for NiN4O2 complexes in electrochemistry over the NiN6 compounds. Further, the coordination studies of 2-mercaptoethanesulfonic acid as a simulator of coenzyme M reductase (CoM) with NiN4 or NiN6 chromophores were discussed.

Stability of ternary copper and nickel complexes with 1,10-phenanthroline

Abstract This work presents a comparative analysis of the behavior of copper(II) and nickel (II) towards the formation of mixed-ligand complexes with 1,10-phenanthroline as primary ligand. Secondary ligands were acetylacetonate, salicylaldehydate (OO donors), glycinate, or tyrosinate (ON donors). The formation of hexacoordinate complexes was observed in the case of nickel. Stability enhancement compared to statistical expectations is found for complexes where the secondary ligand is an OO donor and for tyrosinate. These observations are explained in terms of a hardness increase in the species M(phen)2+, as compared to M2+, due to the well-known π-acceptor behavior of aromatic imines, which makes the first species more attractive to harder ligands as oxygen donors. In the case of tyrosinate, increase in stability is attributed to a hydrophobic interaction between the phenolic group and 1,10-phenanthroline.

Hydrogen-ion driven molecular motions in Cu2+-complexes of a ditopic phenanthrolinophane ligand.

One of the first kinetic evaluations of a metal ion interchange between the two coordination sites of a ditopic macrocycle is presented.

Template reaction of [Ni(ben)3](ClO4)2 with acetone. Crystal structure of 1,11-bis-benzyl-5,7,7-trimethyl-1,4,8,11-tetra-aza-undeca-4-ene nickel(II) perchlorate

Abstract The template synthesis of a new open-chain tetra-aza ligand derived from N-benzylethylenediamine is reported. X-ray structural analysis of the title compound has been determined. 13C CP-MAS NMR for the [Ni(benacet)](ClO4)2 complex was made and assignment of the signals was carried out by the use of the open gate decoupling technique and by comparison with the Ni(II) and Zn(II) complexes of the trans-[14]diene ligand as well as with the perchlorate salt of the free macrocycle. Based on the type of isolated compound, a hypothesis of the possible mechanism of reaction that explains the formation of the mesityl moiety during the template reaction is discussed. This hypothesis could also be used to explain how in the original reaction made by Curtis, a mixture of cis- and trans-isomers are formed.