Characterization of alkyl-cobalamins formed on trapping of epoxide metabolites of 1,3-butadiene

Analytical methods facilitating studies of electrophilically reactive and genotoxic compounds in vitro and in vivo are needed. The strong nucleophile, cob(I)alamin, formed by reduction of Vitamin B12 [cob(III)alamin], may be used for trapping and analysis of 1,2-epoxides and other electrophiles. In the present study, cob(I)alamin is evaluated as an analytical tool for 1,2-epoxide metabolites (oxiranes) of 1,3-butadiene. Products of reaction of cob(I)alamin with 1,2-epoxy-3-butene (EB), 1,2:3,4-diepoxybutane (DEB), and 1,2-epoxy-3,4-butanediol (EBdiol) have been analyzed by reversed phase high performance liquid chromatography (HPLC) coupled on-line to electrospray ionization mass spectrometry (ESI-MS) and ultraviolet diode array detection (UV-DAD). It was shown that a specific alkyl-CbI complex is formed for each metabolite and that it was possible to discriminate between the products by HPLC-UV and by LC-MS. Quantification of DEB with the method by use of another 1,2-epoxide as an internal standard was successfully performed. The possibility of using cob(I)alamin for trapping and analysis of the three oxirane metabolites of 1,3-butadiene will facilitate quantitative comparisons of species in vitro with regard to metabolism of 1,3-butadiene.     

Metal Complexes with Macrocyclic Ligands. PartXLV Axial coordination tendency in reinforced tetraazamacrocyclic complexes

The Cu²⁺ and Ni²⁺ complexes of three reinforced tetraazamacrocycles, containing a piperazine subunit and one or two alkyl substituents at the other two N-atoms have been prepared and their structural properties studied. In solution, the Ni²⁺ complexes are square-planar and show no tendency to axially coordinate a solvent molecule or an N ion. In contrast, the Cu²⁺ complexes change their geometry depending upon the donor properties of the solvent, being square-planar in MeNO₂ and pentacoordinate in DMF. They also easily react in aqueous solution with N to give ternary species with pentacoordinate geometry, the stabilities of which have been determined. In the solid state, the X-ray crystal structures of three Cu²⁺ complexes also show both geometrical arrangements, two having a square-planar, the other one a distorted square pyramidal geometry. The difference behavior of Ni²⁺ and Cu²⁺ stems from the fact that the structural change from square-planar to square-pyramidal can easily be accomplished for Cu²⁺, whereas, for Ni²⁺, it is accompanied by an electronic rearrangement from the low-spin to the high-spin configuration. The relatively rigid ligands cannot Adapt to the somewhat larger high-spin Ni²⁺ion.     

The ground-state potential curve for F2

The ground-state potential curve for F₂ has been obtained using large-scale MC SCF and CI methods. MC SCF curves were obtained with the CAS SCF method using a variety of sets of active orbitals. The main conclusion from the CAS SCF calculations is that the 2π_u orbital is important. CI curves were obtained using the contracted CI method. The largest calculations contained 312000 configurations proper spin and space (d_2h) symmetry. The main conclusions from the CI calculations are that the configuration XXX are important, otherwise errors in D_e of 0.3 eV and in r_e of 0.02 Å are found. The remaining errors at the CI level are 0.08 eV for D_e, 0.005 Å for r_e and less than 10 cm^?1 for the lowest vibrational levels.     

A density functional study of O-O bond cleavage for a biomimetic non-heme iron complex demonstrating an Fe(v)-intermediate

Density functional theory using the B3LYP hybrid functional has been employed to investigate the reactivity of Fe(TPA) complexes (TPA = tris(2-pyridylmethyl)amine), which are known to catalyze stereospecific hydrocarbon oxidation when H(2)O(2) is used as oxidant. The reaction pathway leading to O-O bond heterolysis in the active catalytic species Fe(III)(TPA)-OOH has been explored, and it is shown that a high-valent iron-oxo intermediate is formed, where an Fe(V) oxidation state is attained, in agreement with previous suggestions based on experiments. In contrast to the analogous intermediate [(Por.)Fe(IV)=O](+1) in P450, the TPA ligand is not oxidized, and the electrons are extracted almost exclusively from the mononuclear iron center. The corresponding homolytic O-O bond cleavage, yielding the two oxidants Fe(IV)=O and the OH. radical, has also been considered, and it is shown that this pathway is inaccessible in the hydrocarbon oxidation reaction with Fe(TPA) and hydrogen peroxide. Investigations have also been performed for the O-O cleavage in the Fe(III)(TPA)-alkylperoxide species. In this case, the barrier for O-O homolysis is found to be slightly lower, leading to loss of stereospecificity and supporting the experimental conclusion that this is the preferred pathway for alkylperoxide oxidants. The difference between hydroperoxide and alkylperoxide as oxidant derives from the higher O-O bond strength for hydrogen peroxide (by 8.0 kcal/mol).     

Metal complexes of macrocyclic ligands. Part XXIII. Synthesis,properties, and structures of mononuclear complexes with 12- and 14-membered tetraazamacrocycle-N,N′,N″,N‴-tetraacetic Acids

The two tetraazamacrocycle-N,N′,N″,N?-tetraacetic acids H₄dota and H₄teta form with Ni²⁺, Cu²⁺, and Zn²⁺ (M²⁺) mononuclear complexes MLH₂ and M′[ML], M′ being an alkaline earth ion. The structures of Ni(H₂dota) and Cu(H₂dota) have been solved by X-ray structure analysis. The metal ions are in a distorted octahedral geometry coordinated by four amino N-atoms and two carboxylates. In the case of Cu²⁺, the distortions are more pronounced than for Ni²⁺ indicating that the Jahn-Teller effect is operating. Starting from these two structures, the coordination geometry of the other complexes is discussed using VIS and IR spectra.     

The use of liquid chromatography/mass spectrometry for quantitative analysis of oxycodone, oxymorphone and noroxycodone in Ringer solution, rat plasma and rat brain tissue

Sensitive and reproducible methods for the determination of oxycodone, oxymorphone and noroxycodone in Ringer solution, rat plasma and rat brain tissue by liquid chromatography/mass spectrometry are described. Deuterated analogs of the substances were used as internal standards. Samples in Ringer solution were analyzed by direct injection of 10 microL Ringer solution diluted by an equal volume of water. The limit of quantification was 0.5 ng/mL and the method was linear in the range of 0.5-150 ng/mL for all substances. To analyze oxycodone and oxymorphone in rat plasma, 50 microL of plasma were precipitated with acetonitrile, and the supernatant was directly injected onto the column. To analyze oxycodone, oxymorphone and noroxycodone in rat plasma, 100 microL of rat plasma were subjected to a C18 solid-phase extraction (SPE) procedure, before reconstituting in mobile phase and injection onto the column. For both methods the limit of quantification in rat plasma was 0.5 ng/mL and the methods were linear in the range of 0.5-250 ng/mL for all substances. To analyze the content of oxycodone, oxymorphone and noroxycodone in rat brain tissue, 100 microL of the brain homogenate supernatant were subjected to a C18 SPE procedure. The limit of quantification of oxycodone was 20 ng/g brain, and for oxymorphone and noroxycodone 4 ng/g brain, and the method was linear in the range of 20-1000 ng/g brain for oxycodone and 4-1000 ng/g brain for oxymorphone and noroxycodone. All methods utilized a mobile phase of 5 mM ammonium acetate in 45% acetonitrile, and a SB-CN column was used for separation. The total run time of all methods was 9 min. The intra-day precision and accuracy were <11.3% and <+/-14.9%, respectively, and the inter-day precision and accuracy were <14.9% and <+/-6.5%, respectively, for all the concentrations and matrices described.     

Oxyl radical required for o-o bond formation in synthetic Mn-catalyst

DFT calculations using the B3LYP functional support the suggestion that the [(terpy)(H(2)O)Mn(IV)(micro-O)(2)Mn(III)(H(2)O)(terpy)](3+) (terpy=2,2':6,2' '-terpyridine) complex functions as a synthetic O(2) catalyst. The calculated barrier for O-O bond formation with water is 23 kcal/mol. In this complex, as well as in models of the oxygen evolving complex in PSII, the active species is a Mn(IV)-oxyl radical. From comparisons with inactive Mn(V)-oxo complexes, it is proposed that radical formation is actually a requirement for O(2) formation activity in Mn-complexes.     

Struktur zweier trans-Bis (N,N-dimethylethylendiamin)kobalt(III)-Komplexe. Simulation der sterischen Ligand-Ligand-Wechselwirkungen durch ein ‘Molecular-Mechanics’-Modell

The Crystal and Molecular Structures of Two trans -Bis(N,N-dimethylethylenediamine)cobalt(III) Complexes. Estimate of Steric Ligand-Ligand Interactions by a Molecular-Mechanics Model Two trans-bis (N,N-dimethylethylenediamine)cobalt(III)m complexes with different axial ligands (SNC^?, NO) have been synthesized starting from the corresponding Co^II-amine species. An X-ray crystal-structure analysis revealed widely differing Co? N bond distances. While for the primary amino groups, as in complexes of unsubstituted bidentate amines, bond distances are close to 196 pm, those for the tertiary amino groups are stretched by ca. 10 pm. The good agreement between the molecular geometry as calculated by a molecular-mechanics model and experimental data suggests that the differences in bond distances must be primarily due to simple steric effects.