Synthesis and reactivity of a (mu-1,1-hydroperoxo)(mu-hydroxo)dicopper(II) complex: ligand hydroxylation by a bridging hydroperoxo ligand

A new tetradentate tripodal ligand (L3) containing sterically bulky imidazolyl groups was synthesized, where L3 is tris(1-methyl-2-phenyl-4-imidazolylmethyl)amine. Reaction of a bis(mu-hydroxo)dicopper(II) complex, [Cu2(L3)2(OH)2]2+ (1), with H2O2 in acetonitrile at -40 degrees C generated a (mu-1,1-hydroperoxo)dicopper(II) complex [Cu2(L3)2(OOH)(OH)]2+ (2), which was characterized by various physicochemical measurements including X-ray crystallography. The crystal structure of 2 revealed that the complex cation has a Cu2(mu-1,1-OOH)(mu-OH) core and each copper has a square pyramidal structure having an N3O2 donor set with a weak ligation of a tertiary amine nitrogen in the apex. Consequently, one pendant arm of L3 in 2 is free from coordination, which produces a hydrophobic cavity around the Cu2(mu-1,1-OOH)(mu-OH) core. The hydrophobic cavity is preserved by hydrogen bondings between the hydroperoxide and the imidazole nitrogen of an uncoordinated pendant arm in one side and the hydroxide and the imidazole nitrogen of an uncoordinated pendant arm in the other side. The hydrophobic cavity significantly suppresses the H/D and 16O/18O exchange reactions in 2 compared to that in 1 and stabilizes the Cu2(mu-1,1-OOH)(mu-OH) core against decomposition. Decomposition of 2 in acetonitrile at 0 degrees C proceeded mainly via disproportionation of the hydroperoxo ligand and reduction of 2 to [Cu(L3)]+ by hydroperoxo ligand. In contrast, decomposition of a solid sample of 2 at 60 degrees C gave a complex having a hydroxylated ligand [Cu2(L3)(L3-OH)(OH)2]2+ (2-(L3-OH)) as a main product, where L3-OH is an oxidized ligand in which one of the methylene groups of the pendant arms is hydroxylated. ESI-TOF/MS measurement showed that complex 2-(L3-OH) is stable in acetonitrile at -40 degrees C, whereas warming 2-(L3-OH) at room temperature resulted in the N-dealkylation from L3-OH to give an N-dealkylated ligand, bis(1-methyl-2-phenyl-4-imidazolylmethyl)amine (L2) in approximately 80% yield based on 2, and 1-methyl-2-phenyl-4-formylimidazole (Phim-CHO). Isotope labeling experiments confirmed that the oxygen atom in both L3-OH and Phim-CHO come from OOH. This aliphatic hydroxylation performed by 2 is in marked contrast to the arene hydroxylation reported for some (mu-1,1-hydroperoxo)dicopper(II) complexes with a xylyl linker.     

Synthesis and evaluation of novel pyrimido-acridone, -phenoxadine, and -carbazole as topoisomerase II inhibitors

As part of a series of studies to discover new topoisomerase II inhibitors, novel pyrimidoacridones, pyrimidophenoxadines, and pyrimidocarbazoles were synthesized, and in vitro and in vivo antitumor activities and DNA-protein and/or DNA-topoisomerase II cross-linking activity as an indicator of topoisomerase II-DNA cleavable complex formation were evaluated. The pyrimidocarbazoles possessed high in vitro and in vivo potencies. Compound 26 (ER-37326), 8-acetyl-2-[2-(dimethylamino)ethyl]-1H-pyrimido[5,6,1-jk]carbazole-1,3(2H)-dione, showed in vitro growth inhibitory activity with respective IC(50) values of 0.049 microM and 0.35 microM against mouse leukemia P388 and human oral cancer KB. In vivo, this compound inhibited the tumor growth of mouse sarcoma M5076 implanted into mice with T/C values of 42% and 13% at 3.13 and 6.25 mg/kg/d respectively without significantly affecting the body weight. In addition, compound 26 (ER-37326) increased the formation of DNA-topoisomerase II cross-linking in P388 cells.     

Adsorption Characteristics in Reversed-Phase Liquid Chromatography Using Ethanol/Water Mixed Solvent

Adsorption characteristics were studied in a reversed-phase liquid chromatography consisting of an octadecylsilyl (ODS)-silica gel and ethanol/water mixture (70/30, v/v), and were compared with corresponding results obtained by using methanol/water and acetonitrile/water mixtures (70/30, v/v) as mobile phase. Similar tendencies were observed for some adsorption characteristics in the three chromatographic systems. However, the magnitude of the characteristics was not entirely identical in the three systems. Surface diffusion was dominant for intraparticle diffusion in the ODS-silica gel particles irrespective of the type of the organic modifiers in mobile phases. A few correlations were confirmed with regard to surface diffusion, i.e., an enthalpy-entropy compensation and a linear free-energy relation. The analogous correlations on surface diffusion phenomena suggest the similarity in the mechanism of surface diffusion in the three chromatographic systems.     

Influence of column radial heterogeneity on peak fronting in linear chromatography.

Using numerical calculations of elution peak profiles, an explanation of the fronting behavior of elution peaks in linear chromatography was found in certain radial distributions of the mobile phase flow velocity and local bed efficiency. Fronting peaks are observed only if the flow velocity is higher in the wall region than in the center part of the column and the local efficiency is lower near the wall than in the center. By contrast, tailing or symmetrical peaks are observed if only the flow velocity or the local efficiency are radially heterogeneous. The degree of peak fronting increases with increasing amplitude of the radial distributions. The influence of the radial heterogeneity of the flow velocity on the degree of peak fronting is more severe for high than for low efficiency columns. An equation is suggested to correlate peak fronting behavior for columns of different efficiencies and a procedure proposed for the estimation of the radial distributions of the flow velocity and the local efficiency by analyzing some characteristics of asymmetric peaks.     

Electron diffraction self-imaging of molecular fragmentation in two-step double ionization of water

We doubly ionize H(2)O by single photon absorption at 43 eV leading to H(+) + OH(+). A direct double ionization and a sequential process in which single ionization is followed by rapid dissociation into a proton and an autoionizing OH(*) are identified. The angular distribution of this delayed autoionization electron shows a preferred emission in the direction of the emitted proton. From this diffraction feature we obtain internuclear distances of 700 to 1100 a.u. at which the autoionization of the OH(*) occurs. The experimental findings are in line with calculations of the excited potential energy surfaces and their lifetimes.     

Three p‐xylene‐solvated pseudopolymorphs of bis[1,3‐bis(pentafluorophenyl)propane‐1,3‐dionato]copper(II)

The Cu²⁺ ions in the title compounds, namely bis[1,3‐bis(pentafluorophenyl)propane‐1,3‐dionato‐κ²O,O′]copper(II) p‐xylene n‐solvate, [Cu(C₁₅HF₁₀O₂)₂]·nC₈H₁₀, with n = 1, (I), n = 2, (II), and n = 4, (III), are coordinated by two 1,3‐bis(pentafluorophenyl)propane‐1,3‐dionate ligands. The coordination complexes of (I) and (II) have crystallographic inversion symmetry at the Cu atom and the p‐xylene molecule in (I) also lies across an inversion centre. The p‐xylene molecules in (I) and (II) interact with the pentafluorophenyl groups of the complex via arene–perfluoroarene interactions. In the crystal of (III), two of the p‐xylene molecules interact with the pentafluorophenyl groups via arene–perfluoroarene interactions. The other two p‐xylene molecules are located on the CuO₄ coordination plane, forming a uniform cavity produced by metal...π interactions.     

Extrathermodynamic Study of Retention Equilibrium in RP-LC Using a C18-Silica Monolithic Stationary Phase

This study is concerned with the explanation of some thermodynamic properties of the retention equilibrium on a C₁₈-silica monolithic column. Pulse response experiments were carried out in a reversed-phase liquid chromatography system using a methanol/water mixture (70/30, v/v) and n-alkylbenzene homologs as the mobile phase and sample compounds, respectively, in the temperature range between 278 and 318 K. The retention equilibrium constant (K _a) was calculated from the first absolute moment of elution peaks. The dependence of K _a on the column temperature was analyzed using the modified van??t Hoff plot proposed by Krug et al. to derive the changes of the Gibbs free energy, the enthalpy and the entropy concerning the retention behavior. First, the presence of a real enthalpy?Centropy compensation (EEC) for the retention equilibrium was demonstrated. Then, a thermodynamic model based on the real EEC was developed to explain the temperature dependence of the linear free energy relationship (LFER) of the retention equilibrium. The model indicates how the slope and intercept of the LFER are correlated with the compensation temperatures and several molecular thermodynamic parameters. The model was effective for explaining the thermodynamic properties of the retention equilibrium of the C₁₈-silica monolithic stationary phase.