Thermodynamic and biodistribution studies of Zn(II), Ca(II), Gd(III) and Cu(II) complexes of 3,3,9,9-tetramethyl-4,8-diazaundecane-2,10-dione dioxime

The thermodynamic equilibria of copper(II), zinc(II), calcium(II) and gadolinium(III) with 3,3,9,9-tetramethyl-4,8-diazaundecane-2,10-dione dioxime (L1) have been studied at 25 degrees C and an ionic strength of 0.15 mol dm(-3). Copper and gadolinium form stable complexes with the ligand while the corresponding zinc species are more than 9 log units less stable. No complexes between calcium and the ligand were detected. The low binding strength of L1 towards zinc is attributed to the square-planar coordination geometry forced on the metal ion by the ligand as revealed by molecular mechanics calculations and molecular dynamics simulations. Speciation calculations, using a computer model of blood plasma, indicate that, despite the high concentration of zinc(II) and calcium(II) in vivo, L1 is able to increase the low-molecular-mass fraction of copper in plasma. Octanol/water partition coefficient of [CuL1H(-1)] indicates that although this species is largely hydrophilic, approximately 6% of the complex goes into the octanol phase and hence may promote dermal absorption of copper by the same amount. The dermal penetration rate is calculated to be 4.0 x 10(-4) mm h(-1). The [CuL1H(-1)] complex, which predominates at pH 7.4, is a poor mimic of native copper-zinc superoxide dismutase. Biodistribution experiments using the 64Cu-labelled [CuL1H(-1)] complex indicate an initial high uptake of this species in the liver followed by redistribution into muscle. Only a small amount is excreted through the urine.     

Molar extinction coefficients of some carbohydrates in aqueous solutions

Molar extinction coefficients of some carbohydrates viz. l-arabinose (C₅H₁₀O₅), d-glucose (C₆H₁₂O₆), d-mannose (C₆H₁₂O₆), d-galactose (C₆H₁₂O₆), d(-) fructose (C₆H₁₂O₆) and maltose (C₁₂H₂₄O₁₂) in aqueous solutions have been determined at 81, 356, 511, 662, 1173 and 1332 keV by gamma ray transmission method in a narrow beam good geometry set-up. These coefficients have been found to depend upon the photon energy following a 4-parameter polynomial. These extinction coefficients for different sugars having the same molecular formula have same values varying within experimental uncertainty. Within concentration ranges studied, Beer-Lambert law is obeyed very well.     

Dichlorocarbene Addition to

In contrast to the terminal phosphinidene complex PhPW(CO)(5) (2), which adds to [5]metacyclophane (1) in a 1,4-fashion, dichlorocarbene preferentially adds in a 1,2-fashion to the formal "anti-Bredt" type double bond of the aromatic ring of 1 to afford the norcaradiene 11b, which immediately rearranges to the bridged cycloheptatriene 12b and further by a [1,5] sigmatropic chlorine migration to the isomeric 13b as the first observable product. More slowly, the latter isomerizes via a dissociative mechanism to give 15b. A computational study supports the notion that the [1,5] chlorine migration in the rearrangement 12b --> 13b, for which an activation barrier of 70.2 kJ mol(-)(1) was calculated, is essentially concerted with minor charge separation. In contrast, the analogous [1,5] chlorine migration in the flat model compound 7,7-dichlorocycloheptatriene (12a) displays features of a dissociative pathway.     

In vitro and in vivo stability investigations of Cu(II), Zn(II), Ca(II) and Gd(III) complexes with N,N'-bis(2-hydroxyiminopropionyl) propane-1,3-diamine

Formation constants of copper(II), zinc(II), calcium(II) and gadolinium(III) with N,N'-bis(2-hydroxyiminopropionyl) propane-1,3-diamine (L2) have been studied at 25 degrees C and an ionic strength of 0.15 mol dm(-3). The reasonably high formation constants of the copper with this ligand are due to the ease with which the metal ion deprotonates the amide moieties. The square-planar coordination of L2 towards copper as predicted from UV-visible data may also account for the high selectivity of L2 towards the metal ion. Octanol/water partition coefficients of Cu(II)-L2 complexes indicate that although these complexes are largely hydrophilic, approximately 1.86% of the [CuL2H(-1)] species goes into the octanol layer and hence may promote dermal absorption of copper with a calculated penetration rate of 1.24 x 10(-5) cm h(-1). The [CuL2H(-1)] complex which predominates at pH 7.4 is a poor mimic of native copper-zinc superoxide dismutase. Blood-plasma simulation studies predict that, despite the high concentration of zinc and calcium in vivo, L2 is able to increase the low-molecular-mass fraction of copper. Biodistribution experiments using 64Cu-labelled [CuL2H(-1)] indicate an initial high uptake of this species in the liver, but it is predominantly excreted through the renal system.     

Solution chemistry of 1,15-bis(N,N-dimethyl)-5,11-dioxo-8-(N-benzyl)-1,4,8,12,15-pentaazapentadecane with metal ions of biological interest-Insights toward active metal ion containing therapeutics and diagnostic agents

The equilibrium constants of Cu(II), Zn(II), Ca(II) and Gd(III) with 1,15-bis(N,N-dimethyl)-5,11-dioxo-8-(N-benzyl)-1,4,8,12,15-pentaazapentadecane (La) have been studied at 25 degrees C and an ionic strength of 0.15 mol dm-3. Copper forms more stable complexes with La than the other metal ions investigated. This is probably due to the ease with which Cu(II) deprotonates the nitrogen donor atoms of the amide groups. UV/Vis spectrophotometric data indicate tetradentate binding of the ligand towards copper in [CuLaH-1] and pentadentate binding in [CuLaH-2]. Octanol-water partition coefficients of Cu(II)-La complexes indicate that although these species are largely hydrophilic, approximately 5.62% of the [CuLaH-1] complex goes into the organic phase. This percentage may promote dermal absorption of copper with a calculated penetration rate of 3.75x10(-4) mm h-1. The [CuLaH-1] species which predominates at pH 7.4 is a poor mimic of native copper-zinc superoxide dismutase. Blood-plasma simulation studies predict that La is unable to increase the low molecular mass copper fraction in vivo. This has been confirmed by biodistribution patterns, which are similar to those of 64CuCl2.     

Thermodynamics of Chromium(VI) Anionic Species Sorption onto Surfactant-Modified Montmorillonite Clay

Batch sorption experiments performed on Cr(VI) species sorption showed a significantly enhanced removal of inorganic hexavalent chromium anionic species from aqueous solution by montmorillonite clays modified with quaternary amine, hexadecyltrimethylammonium (HDTMA) bromide. Unmodified clay had no affinity for chromium(VI) species. The sorption of Cr(VI) species has been carried out as a function of pH, contact time, adsorbate concentration (4.14x10(-5) to 8.62x10(-3) M), and temperature (5-45 degrees C). The surfactant-modified clay surface was stable when exposed to extremes in pH. The optimum pH for maximum sorption of Cr(VI) species was found to be at pH 1 and was constant between pH 2 and pH 6. The sorption data obtained was well described by DKR and Langmuir sorption isotherms. Sorption energy (E) for (i) surfactant sorption by montmorillonite clay and (ii) sorption of chromium(VI) species by surfactant modified clay have been computed from the DKR equation. Sorption energy evaluated for the sorption of both surfactant and Cr(VI) species showed that an ion-exchange mechanism was operative. The mechanism of retention appears to be replacement of counterion of the surfactant by Cr(VI) anionic species. Adsorbent capacity for the sorption of Cr(VI) species has been evaluated from the Langmuir sorption isotherm data. Thermodynamic parameters (Delta H degrees, Delta S degrees and Delta G degrees ) for surfactant sorption on montmorillonite clay and Cr(VI) sorption by modified clay have been evaluated. The specific rate constant for sorption of Cr(VI) species on modified montmorillonite was rapid during the first 10 min and equilibrium was found to be attained within 30 min. The sorption of Cr(VI) species onto modified montmorillonite clay followed first-order rate kinetics. Copyright 2000 Academic Press.