Víctor M. Ugalde-Saldívar

A dicopper complex with distant metal centers. Structure, magnetic properties, electrochemistry and catecholase activity.

The crystal structure and magnetic properties of a dinuclear copper(II) complex of the ligand [2,8-dimethyl-5,11-di-(dimethylethyleneamine) 1,4,5,6,7,10,11,12-octahydroimidazo [4,5-h] imidazo [4,5-c] [1,6]diazecine] dimeim have been investigated. Also, its catecholase activity has been explored in different solvent mixtures: MeCN/H2O and OH/H2O, each at several pH values. In CH3OH/H2O, where the activity was superior, the optimal pH value for the catalytic activity was found to be lower than in CH3CN/H2O. The study of the complexs electrochemical behavior (cyclic voltammetry) which was also investigated in these various media, revealed that although an increase in pH in both solvent mixtures results in an increase both in Me oxidizing power (E(1/2)) and reversibility (ipa/ipc) the change of solvent system seems to be a more influencing factor. The superior catalytic activity found in MeOH/H2O pH=8.0, is associated with a significantly more reversible behavior displayed in this medium. Potentiometric determination of the overall formation constant and three successive pKas for the complex, suggest the formation of stable hydroxo complexes which could be the catalytically active species.

Structural, spectroscopic, and electrochemical properties of tri- and tetradentate N3 and N3S copper complexes with mixed benzimidazole/thioether donors

Cupric and cuprous complexes of bis(2-methylbenzimidazolyl)(2-methylthiophene)amine (L(1)), bis(2-methylbenzimidazolyl)benzylamine (L(2)), bis(2-methylbenzimidazolyl)(2,4-dimethylphenylthioethyl)amine (L(3)), bis(1-methyl-2-methylbenzimidazolyl)benzylamine (Me(2)L(2)), and bis(1-methyl-2-methylbenzimidazolyl)(2,4-dimethylphenylthioethyl)amine (Me(2)L(3)) have been spectroscopically, structurally, and electrochemically characterised. The thioether-containing ligands L(3) and Me(2)L(3) give rise to complexes with Cu-S bonds in solution and in the solid state, as evidenced by UV-vis spectroscopy and X-ray crystallography. The Cu(2+) complexes [L(1)CuCl(2)] (1), [L(2)CuCl(2)] (2) and [Me(2)L(3)CuCl]ClO(4) (3(Me,ClO4)) are monomeric in solution according to ESI mass spectrometry data, as well as in the solid state. Their Cu(+) analogues [L(1)Cu]ClO(4), [L(2)Cu]ClO(4), [L(3)Cu]ClO(4) (4-6), [BOC(2)L(1)Cu(NCCH(3))]ClO(4) (4(BOC)), [Me(2)L(2)Cu(NCCH(3))(2)]PF(6) (5(Me)) and [Me(2)L(3)Cu](2)(ClO(4))(2) (6(Me)) are also monomeric in acetonitrile solution, as confirmed crystallographically for 4(BOC) and 5(Me). In contrast, 6(Me) is dimeric in the solid state, with the thioether group of one of the ligands bound to a symmetry-related Cu(+) ion. Cyclic voltammetry studies revealed that the bis(2-methylbenzimidazolyl)amine-Cu(2+)/Cu(+) systems possess half-wave potentials in the range -0.16 to -0.08 V (referenced to the ferrocenium-ferrocene couple); these values are nearly 0.23 V less negative than those reported for related bis(picolyl)amine-derived ligands. Based on these observations, the N(3) or N(3)S donor set of the benzimidazole-derived ligands is analogous to previously reported chelating systems, but the electronic environment they provide is unique, and may have relevance to histidine and methionine-containing metalloenzymes. This is also reflected in the reactivity of [Me(2)L(2)Cu(NCCH(3))(2)](+) (5(Me)) and [Me(2)L(3)Cu](+) (6(Me)) towards dioxygen, which results in the production of the superoxide anion in both cases. The thioether-bound Cu(+) centre in 6(Me) appears to be more selective in the generation of O(2)˙(-) than 5(Me), lending evidence to the hypothesis of the modulating properties of thioether ligands in Cu-O(2) reactions.

Copper versus thioether-centered oxidation: mechanistic insights into the non-innocent redox behavior of tripodal benzimidazolylaminothioether ligands.

A series of Cu(+) complexes with ligands that feature varying numbers of benzimidazole/thioether donors and methylene or ethylene linkers between the central nitrogen atom and the thioether sulfur atoms have been spectroscopically and electrochemically characterized. Cyclic voltammetry measurements indicated that the highest Cu(2+)/Cu(+) redox potentials correspond to sulfur-rich coordination environments, with values decreasing as the thioether donors are replaced by nitrogen-donating benzimidazoles. Both Cu(2+) and Cu(+) complexes were studied by DFT. Their electronic properties were determined by analyzing their frontier orbitals, relative energies, and the contributions to the orbitals involved in redox processes, which revealed that the HOMOs of the more sulfur-rich copper complexes, particularly those with methylene linkers (-N-CH2-S-), show significant aromatic thioether character. Thus, the theoretically predicted initial oxidation at the sulfur atom of the methylene-bridged ligands agrees with the experimentally determined oxidation waves in the voltammograms of the NS3- and N2S2-type ligands as being ligand-based, as opposed to the copper-based processes of the ethylene-bridged Cu(+) complexes. The electrochemical and theoretical results are consistent with our previously reported mechanistic proposal for Cu(2+)-promoted oxidative C-S bond cleavage, which in this work resulted in the isolation and complete characterization (including by X-ray crystallography) of the decomposition products of two ligands employed, further supporting the novel reactivity pathway invoked. The combined results raise the possibility that the reactions of copper-thioether complexes in chemical and biochemical systems occur with redox participation of the sulfur atom.

Solvent and pH effects on the redox behavior and catecholase activity of a dicopper complex with distant metal centers

A dicopper complex is described for which significant catecholase activity was found, particularly for a compound in which the two metal ions are more than 7A apart. Variations on the catecholase activity of this complex were explored in a range of pH values from 5.5 to 9.0 in two solvent mixtures, MeCN/H(2)O and MeOH/H(2)O. The catalytic performance of the complex was found to be substantially better in the second, where the maximum activity was achieved at a pH value one unit lower than in the first. Electrochemical studies of the complex in the absence and presence of dioxygen revealed a very different behavior in each of the two solvent mixtures, which may account for the correspondingly distinct catalytic activity.

Spin Crossover Behavior in a Series of Iron(III) Alkoxide Complexes

The synthesis, crystal structures, magnetic behavior, and electron paramagnetic resonance studies of five new Fe(III) spin crossover (SCO) complexes are reported. The [Fe(III)N5O] coordination core is constituted of the pentadentate ligand bztpen (N5) and a series of alkoxide anions (ethoxide, propoxide, n-butoxide, isobutoxide, and ethylene glycoxide). The methoxide derivative previously reported by us is also reinvestigated. The six complexes crystallize in the orthorhombic Pbca space group and show similar molecular structures and crystal packing. The coordination octahedron is strongly distorted in both the high- and low-temperature structures. The structural changes upon spin conversion are consistent with those previously observed for [Fe(III)N4O2] SCO complexes of the Schiff base type, except for the Fe-O(alkoxide) bond distance, which shortens significantly in the high-spin state. Application of the Slichter-Drickamer thermodynamic model to the experimental SCO curves afforded reasonably good simulations with typical enthalpy and entropy variations ranging in the intervals ΔH = 6-13 kJ mol(-1) and ΔS = 40-50 J mol(-1) K(-1), respectively. The estimated values of the cooperativity parameter Γ, found in the interval 0-2.2 kJ mol(-1), were consistent with the nature of the SCO. Electron paramagnetic resonance spectroscopy confirmed the transformation between the high-spin and low-spin states, characterized by signals at g ≈ 4.47 and 2.10, respectively. Electrochemical analysis demonstrated the instability of the Fe(II) alkoxide derivatives in solution.

Electrocatalytic Proton Reduction by Dimeric Nickel Complex of a Sterically Demanding Pincer-type NS2 Aminobis(thiophenolate) Ligand

Basic methanolysis of a sterically hindered aminobis(S-arylthiocarbamate) affords a novel aminobis(thiophenolate) pincer-type ligand NS22–; the in situ generated dianion reacts cleanly with Ni2+ and Zn2+ resulting in dimeric complexes with bridging thiophenolate ligands, as determined spectroscopically and by X-ray crystallography. The C2-symmetric [Ni(NS2)]2 dimer (1) has a square planar coordination geometry around the Ni2+ ions, while the [Zn(NS2)]2 analogue (2) is characterized by a distorted tetrahedral geometry around each independent Zn2+ ion. Addition of the neutral monodentate donor L = 2,6-xylylisocyanide to [Ni(NS2)]2 affords the monomeric complex [LNi(NS2)] (3), which is characterized in the solid state by a square planar geometry with the isocyanide donor trans to the tertiary amine of NS2. The pincer NS2 ligand provides redox plasticity to 1, manifested in the accessibility of the putative Ni+Ni+ and Ni3+Ni3+ dimeric complexes, based on comparative cyclic voltammetry studies with 2 and 3. The redox properties of 1 endow it with hydrogenase-type activity, as evidenced in the electrocatalytic reduction of protons in a mixed aqueous/organic phase, as well as the oxidation of hydrides from NaBH(OAc)3. Both 1 and 3 are resilient under protic and oxidative conditions, as evidenced in reactivity tests monitored by UV–vis spectroscopy.

Dinuclear copper complexes with imidazole derivative ligands: a theoretical study related to catechol oxidase activity.

Catechol oxidase is a very important and interesting metalloprotein. In spite of the efforts to understand the reaction mechanism of this protein, there are important questions that remain unanswered concerning the catalytic mechanism of this enzyme. In this article, dinuclear copper compounds are used as biomimetic models of catechol oxidase to study plausible reaction paths. These dinuclear copper(II) complexes have distant metal centers (of 7.5 Å approximately) and superior catalytic activity to that of many dicopper complexes with shorter Cu-Cu distances. One mononuclear copper(II) complex is also analyzed in this investigation in order to see the influence of the two metal centers in the catalytic activity. Density functional theory calculations were performed to obtain optimized structures, vertical ionization energies, vertical electron affinities, the electrodonating power (ω(-)), the electroaccepting power (ω(+)) and the energy difference of several reaction paths. The K(M) experimental results that were previously reported compare well with the electroaccepting power (ω(+)) of the copper compounds that are included in this article, indicating that this index is useful for the interpretation of the electron transfer capacity and therefore the catalytic activity. The catechol moiety coordinates to only one Cu ion, but two metal atoms are needed in order to have a good electron acceptor capacity of the biomimetic models.

Novel iron(II) complexes with hexadentate nitrogen ligands obtained via intramolecular redox reactions

Two novel complexes: [Fe(L2′)][BPh4]2, 1, and [Fe(L3′)][BPh4]2, 2, with the hexadentate nitrogen ligands, Ln′ = 1,9-bis(2′-pyridyl)-5-[(R-2″-pyridyl)methyl]-2,5,8-triazanon-1-ene, where R = ethoxy for L2′ and methoxy for L3′, were obtained from the iron(III) complex of the pentadentate ligand, L1 = 1,9-bis(2′-pyridyl)-2,5,8-triazanonane. Complexes 1 and 2 were also obtained by making the hexadentate ligands: 1,9-bis(2′-pyridyl)-5-[(ethoxy-2′-pyridyl)methyl]-2,5,8-triazanonane (L2) and 1,9-bis(2′-pyridyl)-5-[(methoxy-2″-pyridyl)methyl]-2,5,8-triazanonane (L3) react with Fe(III), respectively. The structures of complexes 1 and 2 were characterized by COSY, HMBC, HMQC and NOESY NMR studies, and both structures were also confirmed by X-ray analysis. In both cases, the geometry around iron is a distorted octahedron. Since 1 and 2 are diamagnetic at 298 K they are low-spin iron(II) species. Both preparative methods are examples of oxidative dehydrogenation of a Fe(III) polyamine complex, in which the thermodynamically and kinetically stable final product is a low spin Fe(II) imine complex. In the case of the first method an increase in the size and denticity of the starting ligand is observed.

Preparation, crystal structure and kinetics of acid hydrolysis of an isomer of [Cr(picdien)Cl][ZnCl4][picdien = 1,9-bis(2′-pyridyl)-2,5,8-triazanonane]

The complex [Cr(picdien)Cl][ZnCl4][picdien = 1,9-bis(2′-pyridyl)-2,5,8-triazanonane] has been prepared and its structure determined by a single-crystal X-ray diffraction study of the triclinic crystals: a= 9.118(3), b= 9.581(5), c= 14.042(5)A, α= 78.04(3), β= 86.37(3)°, and γ= 76.56(3)°. The complex cation has the anti-αβ configuration. The kinetics of aquation of the perchlorate salt has been studied in dilute aqueous nitric acid solution, [complex]= 5 × 10–3 mol dm–3. The rate constants are independent of [H+] over the range 0.10 < [H +] < 0.001 mol dm–3; k25°C= 6.0 × l0–6s–1, ΔH‡= 93.1 ± 2.2 kJ mol–1, ΔS‡=–32.9 ± 6.9 J K–1 mol–1.

Electrochemical strategy to scout 1,4-naphthoquinones effect on voltage gated potassium channels

Naphthoquinone (NQ) was tested on voltage-gated ion channels expressed in Xenopus laevis oocytes. The activity of potassium Shaker channel with Inactivation domain Removed (ShIR) was not affected; in contrast, NQ diminished Kv1.3 currents. A current decrease was barely observed with the oxidant H(2)O(2). These findings suggested that redox properties were involved in the naphthoquinone-Kv1.3 channel interaction. NQ and some derivatives (NQs) were characterized in DMSO and physiological (ND-96) media by cyclic voltammetry. A typical two-stage mono-electronic reduction mechanism was observed in DMSO, while a one-stage bi-electronic reduction process was found in ND-96 medium. NQs with the lowest and the highest redox potential values were tested on both channels. Voltage-clamp recordings showed that inhibition of Kv1.3 was dependent on NQs redox potential. Results demonstrated that structural features (aromaticity and substituents prone to hydrogen bonds formation) of NQs were also important. This effect could be explained by interactions of some channel residues with NQs that contribute to favor their reduction process in the protein surroundings. The electrochemical strategy presented to simulate the cellular environments (aqueous and non-aqueous) that NQs may face, is an important contribution to pre-select (in a fine and simple way) the best redox compounds for electrophysiological testing.