Luis Ortiz-Frade

Coexistence of Intramolecular Ligand-Mediated and Through Hydrogen-Bond Magnetic Interactions in a Chain of Dicopper(II) Units

The reaction of 2,8-dimethyl-5,11-bis(pyridin-2-ylmethyl)-1,4,5,6,7,10,11,12-octahydroimidazo[4,5-h]imidazo[4,5-c][1,6]-diazecine (dimp) with copper(II) nitrate in water produces the compound [Cu(2)(dimp)(H(2)O)(2)(NO(3))(2)](NO(3))(2). The single-crystal X-ray structure shows the formation of hydrogen-bonded chains in the lattice that are formed by dicopper(II) units doubly connected by nitrate/water bridges. Within the one-dimensional chains, the Cu ions are separated by either intramolecular or intermolecular distances of 7.309(2) Å or 6.255(2) Å, respectively. The magnetic susceptibility data revealing weak antiferromagnetic exchange interactions between the copper(II) ions were interpreted by considering two possible models, namely, an isolated dinuclear and a 1-D chain picture. The latter leads to an alternation J(1) = -11.6 and J(2) = -3.0 cm(-1) along the chain. In order to clarify the relative strengths of the exchange couplings through hydrogen bonds and via the bridging dimp ligand, solution EPR studies and quantum chemical calculations were carried out. EPR studies unambiguously conclude on the existence of an exchange interaction J(a) mediated by the dinucleating dimp ligand, while the through-H coupling J(b) is physically absent in solution. On the basis of dinuclear units extracted from the X-ray data, J(a) was estimated around -5.0 cm(-1) from DFT-based calculations (M06 functional), whereas J(b) is negligible. In contrast, wave function configuration interaction calculations (DDCI) support a description where both inter- and intramolecular pathways coexist with a preeminent role of H bonds with J(a) = -2.8 and J(b) = -10.4 cm(-1). Not only are these values very consistent with the extracted set of parameters (J(1), J(2) = -11.6, -3.0 cm(-1)) but the possibility to generate leading exchange coupling through weak bonds is evidenced by means of wave function-based calculations.

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.

4-Ferrocenylpyridine- and 4-Ferrocenyl-3-ferrocenylmethyl-3,4-dihydropyridine-3,5-dicarbonitriles: Multi-Component Synthesis, Structures and Electrochemistry

The reactions of 2-cyano-3-ferrocenylacrylonitrile (1) with malononitrile (2) in a MeOH/H2O or 2-PrOH/H2O medium in the presence of Na2CO3 afforded 6-alkoxy-2-amino-4-ferrocenylpyridine-3,5-dicarbonitriles 3a,b (multi-component condensation) and 6-alkoxy-2-amino-4-ferrocenyl-3-ferrocenylmethyl-3,4-dihydropyridine-3,5-dicarbonitriles 4a,b (multi-component cyclodimerization). Analogous reactions of 1 with 2 in an MeOH/H2O medium in the presence of NaOH, piperidine, or morpholine gave compounds 3a, 4a and 2-amino-4-ferrocenyl-6-hydroxy-, 6-piperidino- and 6-morpholinopyridine-3,5-dicarbonitriles 3c–e, respectively. The structures of the compounds 3b, 4a and 4b were established by the spectroscopic data and X-ray diffraction analysis. The electrochemical behaviour of compounds 3b, 3d and 4b was investigated by means of cyclic voltammetry.

Reactions of Diferrocenylmorpholino- and -Methylsulfanyl-cyclopropenylium Salts with β-Dicarbonyl Compounds and Diethyl Malonate

2,3-Diferrocenyl-1-morpholinocyclopropenylium tetrafluoroborate reacts with ethyl acetoacetate, ethyl benzoylacetate, and diethyl malonate in the presence of triethylamine to yield 3-[acyl(ethoxycarbonyl)]-, 3-(diethoxycarbonyl)-methyl-3-morpholino-1,2-diferrocenylcyclopropenes (3a–c), and 3-[acyl(ethoxycarbonyl)]- and (diethoxycarbonyl)-methylidene-1,2-diferrocenylcyclopropenes (4a–c) in a ca. 1:1.5 ratio. 2,3-Diferrocenyl-1-methylsulfanylcyclopropenylium iodide with the same substrates affords compounds 4a,b (∼10–15%), 3-[acyl(ethoxycarbonyl)]methyl-3-methylsulfanyl-1,2-diferrocenylcyclopropenes (5a,b) (∼8–10%), 2-acyl-3,4-diferrocenyl-5-methylsulfanylcyclopentadienones (6a,b), ethyl 2-acyl-3,4-diferrocenyl-5-methylsulfanylpenta-2,4-dienoates (7a,b; 8a,b), and ethyl 3,4-diferrocenyl-2-methylsulfanyl-6-oxohexa(hepta)-2,4-dienoates (9a,b). The spatial structure of ethyl Z,E-3,4-diferrocenyl-2-methylsulfanyl-6-oxohepta-2,4-dienoate (9b) was established based on the data from x-ray diffraction analysis. Electrochemical properties of 3-[acyl(ethoxycarbonyl)]- and (diethoxycarbonyl)-methylidene-1,2-diferrocenylcyclopropenes (4a–c) are studied.

Potential Amoebicidal Activity of Hydrazone Derivatives: Synthesis, Characterization, Electrochemical Behavior, Theoretical Study and Evaluation of the Biological Activity

Four new hydrazones were synthesized by the condensation of the selected hydrazine and the appropriate nitrobenzaldehyde. A complete characterization was done employing 1H- and 13C-NMR, electrochemical techniques and theoretical studies. After the characterization and electrochemical analysis of each compound, amoebicidal activity was tested in vitro against the HM1:IMSS strain of Entamoeba histolytica. The results showed the influence of the nitrobenzene group and the hydrazone linkage on the amoebicidal activity. meta-Nitro substituted compound 2 presents a promising amoebicidal activity with an IC50 = 0.84 μM, which represents a 7-fold increase in cell growth inhibition potency with respect to metronidazole (IC50 = 6.3 μM). Compounds 1, 3, and 4 show decreased amoebicidal activity, with IC50 values of 7, 75 and 23 µM, respectively, as a function of the nitro group position on the aromatic ring. The observed differences in the biological activity could be explained not only by the redox potential of the molecules, but also by their capacity to participate in the formation of intra- and intermolecular hydrogen bonds. Redox potentials as well as the amoebicidal activity can be described with parameters obtained from the DFT analysis.

Synthesis, characterization and evaluation of the substituent effect on the amoebicide activity of new hydrazone derivatives

A series of 10 hydrazones were synthesized by condensation of the selected hydrazine and the appropriate aldehyde. After the characterization and electrochemical analysis of each compound, amoebicidal activity was evaluated in vitro against the HM1:IMSS strain of Entamoeba histolytica. The results showed the influence of the nitrobenzene group and the hydrazone linkage over the amoebicidal activity. Compound 1 presents a promising amoebicidal activity with an IC50 = 0.98 μM, which represents a 7-fold increase in the potency of cell growth inhibition with respect to metronidazole (IC50= 6.8 μM). Moreover, compounds 2 and 4 present an amoebicidal activity comparable to the reference compound. These results show that the electronic environment of hydrazone derivatives reflected in redox potential values of the hydrazone linkage and the nitro group plays a fundamental role in the amoebicidal activity. The molecular structure of compound 1 was reported.

Aqua­[1,8-bis­(pyridin-2-yl)-3,6-dithia­octane-κ4N,S,S′,N′]copper(II) dinitrate acetonitrile monosolvate

In the title compound, [Cu(C16H20N2S2)(H2O)](NO3)2·CH3CN, the CuII atom displays a distorted square-pyramidal coordination, in which a water molecule occupies the apical position and the basal plane is formed by two N atoms and two S atoms of a 1,8-bis(pyridin-2-yl)-3,6-dithiaoctane ligand. The crystal packing is stabilized by O—H⋯O and C—H⋯O hydrogen bonds.

Intramolecular Conversions of (Aminoferrocenylpenta-1,4-dienyl)-ferrocenylcarbenes: Synthesis of Diferrocenylmono-, bi-, tricycles and Amino(diferrocenyl)hexa-1,3,5-trienes

Synthesis of 3,4-diferrocenyltoluene (7), 1-morpholino- and 1-piperidino-2,3-diferrocenylbicyclo[3.1.0]hex-2-enes 8a, 8b, 1-morpholino- and 1-piperidino-7-ferrocenyl-3,4-ferrocenobicyclo[3.2.1]oct-6-enes 9a, 9b, 2- and 3-amino(diferrocenyl)-hexa-1,3,5-trienes 10a,b, 11a,b by reactions of amino(diferrocenyl)cyclopropenylium tetrafluoro-borates with 1-methylprop-2-enylmagnesium chloride at 80 °C is described. The structures of the compounds obtained were determined by IR, 1H- and 13C-NMR spectroscopy and mass spectrometry. X-ray diffraction data for 1-piperidino-7-ferrocenyl-3,4-ferroceno-bicyclo[3.2.1]oct-6-ene (9b), 2-morpholino- and 2-piperidino-1,3-diferrocenyl-4-methyl-hexa-1,3,5-trienes 10a and 10b is presented. The electrochemical behaviour of compounds 7, 8a, 10a and 10b was investigated by means of cyclic voltammetry and square wave voltammetry. For 7 and 8a two electrochemical processes (I-II), attributed to the oxidation of the ferrocene moieties were found. On the other hand for compounds 10a and 10b a single electron transfer for both ferrocene groups and the electrochemical generation of the monocation and dication species were detected.

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.

Platinum complexes with non-symmetric fluorodithioethers: Molecular structures of cis-[PtCl2(CH3SCH2CH 2SRf)] (Rf = C6F5, C6H4F-3) and trans-[PtCl2(CH3SCH2CH 2SC6F5)2]

This paper describes the synthesis and characterization of the non-symmetric ligands CH3SCH2CH2SRf (Rf = C6F5, C6HF4-4, C6H4F-2, C6H4F-3, C6H4F-4) as well as their platinum(II) derivatives cis-[PtCl2(CH3SCH2CH2SR f)] (Rf = C6F5, C6HF4-4, C6H4F-2, C6H4F-3, C6H4F-4) and trans-[PtCl2(CH3SCH2CH 2SRf)2] (Rf = C6F5, C6HF4-4). 19F NMR of these complexes show the presence of syn and anti isomers, consistent with a fast flipping of the metallacycle ring and a slow inversion of configuration at the dithioether sulfur atoms. The molecular and crystalline structures of the compounds cis-[PtCl2(CH3SCH2CH2SC 6F5)], cis-[PtCl2(CH3SCH2CH2SC 6H4F-3)] and trans-[PtCl2(CH3SCH2CH 2SC6F5)2], solved by X-ray diffraction are also described.