Novel metal-linked face-to-face porphyrazine dimer

We report the synthesis and physical studies of a novel porphyrazine (pz) dimer [1[Ni,Cu]]2, which has Ni(II) ions incorporated into the pz cores and is linked by two Cu(II) ions coordinated to bis(picolinamide) chelates attached to the pz periphery. [1[Ni,Cu]]2 was prepared from precursor pz 2 with a selenodiazole ring fused to the pz core. This ring was deprotected to form the diamino-pz 3, which reacted with 2 mol of picolinoyl chloride hydrochloride to form pz 1[2H,2H], with peripheral bis(picolinamide) chelates; this was metalated to form [1[Ni,Cu]]2. The crystal structures of 1[2H,2H] and [1[Ni,Cu]]2 are presented. The latter is a dimer in which parallel, face-to-face pz's with an average separation of 3.30 angstroms are linked through the peripheral picolinamide ligands by a pair of peripheral Cu(II) ions. Each Cu(II) is coordinated with distorted square-planar geometry by a picolinamide from each pz. In this report, we focus on the interaction of these two peripheral Cu(II) ions. We discuss the preparation and magnetic properties of the pz dimer complex [1[Ni,Cu]]2 with two Cu(II) ions in the peripheral chelate but a diamagnetic metal ion Ni(II) in the pz core. Although [1[Ni,Cu]]2 contains two Cu(II) ions (S = 1/2), we could detect no electron paramagnetic resonance signal, which suggests very strong antiferromagnetic exchange between those two Cu(II) ions. Temperature-dependent magnetic susceptibility measurement gives an exchange splitting between the S = 0 ground state and the excited triplet state of delta = 660 cm(-1).     

The reactive states of ions: Octatrienes and dimethyl substituted cyclohexadienes

The principal decomposition routes of molecular ions of cis, cis, cis-2,4,6-octatriene, cis, cis, trans-2,4,6-octatriene, trans, cis, trans-2,4,6-octatriene, trans-5,6-dimethyl-1,3-cyclohexadiene and cis-5,6-dimethyl-1,3-cyclohexadiene were studied using ion kinetic spectroscopy. The loss of radicals from [M]⁺· appears to proceed via a ground state, while loss of a neutral molecule appears to involve either complete equilibration of structure within the system or both ground state and excited state pathways.     

Changing DNA grooves--a 1,4,5,8-naphthalene tetracarboxylic diimide bis-intercalator with the linker (beta-Ala)(3)-Lys in the minor groove

We have been investigating a modular, threading DNA polyintercalator design based upon the 1,4,5,8-naphthalene tetracarboxylic diimide (NDI) intercalating unit. Previously, we have reported the NMR analysis of a bis-intercalator-DNA complex in which the peptide linker between NDI units was found to occupy the DNA major groove (Guelev, Lee, Sorey, Hoffman, Iverson, Chem. Biol. 2001, 8, 415-425). Here we describe the NMR analysis of a complex between a related bis-intercalator known to display altered DNA sequence specificity. In this case, the linker resides in the DNA minor groove. We have thus shown that within this set of sequence specific bis-intercalators, both DNA grooves can be accessed, setting the stage for longer threading polyintercalators designed to have linkers occupying both grooves in an alternating fashion.     

The determination of all the platinum group elements and gold in rocks and ore by neutron activation analysis after preconcentration by a nickel sulphide fire-assay technique on large samples

The noble metals are inhomogeneously distributed in sulphide ores and their host rocks. It is therefore necessary to analyse large sample sizes to obtain representative analyses. A nickel sulphide fire assay technique has been adapted to extract the noble metals from a large sample size (50 g) into a nickel sulphide button. Subsequently the fire assay button is dissolved in hydrochloric acid and the solution is filtered. The noble metal residue retained on the filter paper is analysed quantitatively by i.n.a.a. techniques. This method is rapid, relatively inexpensive and has better sensitivities for all the noble metals than other analytical techniques.     

ANION AND SOLVENT EFFECTS ON THE RATE OF REDUCTION OF TRIPLET EXCITED THIAZINE DYES BY FERROUS IONS

Abstract— The lifetimes of the triplet excited states of thionine and methylene blue were measured in aqueous and 50 v/v% aqueous acetonitrile solutions acidified with 0.01 N sulfuric or trifluoromethyl-sulfonic acid. The rate constants for reaction of the triplet excited dyes with ferrous ions were measured in the same solutions. The triplet lifetimes in the absence of added quenchers were insensitive to a change in acid from trifluoromethylsulfonic to sulfuric or to a change in solvent from water to 50v/v% aqueous acetonitrile (τ for triplet thionine ˜7.5 μs, τ for triplet methylene blue ˜4.5 μs). In contrast, the rate constant for reaction of the triplet dyes with ferrous ions increased by nearly a factor of 10 with a change in acid from trifluoromethylsulfonic to sulfuric. In solutions containing sulfate ions this reaction rate constant increased with increasing sulfate concentration and with a change in solvent from water to 50 v/v% aqueous acetonitrile. The results are discussed in terms of the possibility of association of the positively charged reactive ions with sulfate anions. Quenching of the triplet excited dyes by ferric ions or by ground state dye molecules was shown to be negligible at the concentration used for the ferrous ion quenching study.     

Phage-display selection of a human single-chain fv antibody highly specific for melanoma and breast cancer cells using a chemoenzymatically synthesized G(M3)-carbohydrate antigen

Overexpression of the cell-surface glycosphingolipid G(M3) is associated with a number of different cancers, including those of the skin, colon, breast, and lung. Antibodies against the G(M3) epitope have potential application as therapeutic agents in the treatment of these cancers. We describe the chemoenzymatic synthesis of two G(M3)-derived reagents and their use in the panning of a phage-displayed human single-chain Fv (scFv) antibody library derived from the blood of cancer patients. Three scFv-phage clones, GM3A6, GM3A8, and GM3A15, were selected for recombinant expression and were characterized using BIAcore and flow cytometry. BIAcore measurements using the purified, soluble scFvs yielded dissociation constants (K(d)) ranging from 4.2 x 10(-7) to 2.1 x 10(-5) M. Flow cytometry was used to evaluate the ability of each scFv to discriminate between normal human cells (human dermal fibroblast, HDFa), melanoma cells (HMV-1, M21, and C-8161), and breast cancer cells (BCM-1, BCM-2, and BMS). GM3A6 displayed cross-reactivity with normal cells, as well as tumor cells, and GM3A15 possessed little or no binding activity toward any of the cell lines tested. However, GM3A8 bound to five of the six tumor cell lines and showed no measurable reactivity against the HDFa cells. Hence, we have demonstrated that a synthetic G(M3) panning reagent can be used to isolate a fully human scFv that is highly specific for native G(M3) on the surface of tumor cells. The result is a significant step toward effective immunotherapies for the treatment of cancer.