The accurate calculation of dipole moments and dipole polarizabilities using Gaussian-based density functional methods

Dipole moments and static dipole polarizabilities have been calculated for a number of small molecules using the linear combination of Gaussian-type orbitals–local spin density method. The effect of augmenting standard orbital basis sets with polarization functions has been investigated. A set of optimum ζ_d, for use in calculating polarizabilities, has been derived for the first-row atoms C, N, O, and F. The results of this optimized doubly polarized double-zeta basis set compare well with results obtained using a double-zeta basis set augmented by four even-tempered ζ_d polarization functions. The results of the optimized basis set, and a basis set augmented with only a single ζ_d polarization function derived from it, compare very favorably with those obtained from Møller–Plesset perturbation theory and with experimental data. They show a marked improvement on results obtained using standard Hartree–Fock self-consistent-field molecular orbital methods where no treatment of electron-correlation is included.     

Molar mass distributions by gradient liquid chromatography: predicting and tailoring selectivity

Interactive liquid chromatography (iLC) for polymer analysis is usually applied to the characterisation of distributions other than molar mass. In particular, its use for the determination of chemical-composition, functionality-type and tacticity distributions has been demonstrated. The application of iLC for the determination of molar mass distributions (MMDs), however, has not yet been fully explored. An expanded version of the reversed-phase liquid chromatography model has been developed to describe and predict how the retention behaviour of polydisperse polystyrene samples changes with molar mass. The relationship between molar mass and the parameters of the model has been investigated in some detail and non-linear correlations were found. From the model and the relationships between the model parameters and molar mass, calibration curves (retention time versus molar mass) were constructed to predict changes in chromatographic selectivity across a given molar mass range. These calibration curves were compared to experimentally obtained curves and, in most cases, excellent agreement was found. The dramatic enhancement in selectivity that can be obtained with iLC in comparison to size-exclusion chromatography (SEC) was illustrated by measuring matrix-assisted laser desorption ionisation (MALDI) MS spectra of fractions collected during a gradient-LC separation. In the low-molar mass range, essentially monodisperse fractions were obtained. Calibration curves, predicted by the model and validated experimentally using narrow-dispersity standards and MALDI-MS spectra of fractions, were used to determine the molar mass distribution of some narrowly distributed polystyrene samples. Molar mass distributions for such standards were found to be somewhat lower than the values reported by the manufacturers. The results also deviated from those obtained by MALDI-MS.     

Measuring intracellular calcium fluxes in high throughput mode

The measurement of intracellular calcium fluxes in real time is widely applied within the pharmaceutical industry to measure the activation of G-protein coupled receptors (GPCRhyp;s), either for pharmacological characterisation or to screen for new surrogate ligands. Initially restricted to G(q) coupled GPCRs, the introduction of promiscuous and chimeric G-proteins has further widened the application of these assays. The development of new calcium sensitive dyes and assays has provided sensitive, homogeneous assays which can be readily applied to high throughput screening (HTS). In this paper we describe the full automation of this assay type using a fluorometric imaging plate reader (FLIPR ) integrated into a Beckman/Sagian system to establish a simple robotic system that is well suited for the current medium throughput screening in this area of lead discovery. Using a recently completed HTS we discuss important determinants for FLIPR based screening, highlight some limitations of the current approach, and look at the requirements for future automated systems capable of keeping up with expanding compound files.     

Synthesis and base hydrolysis kinetics of the nitrile complexes [Co(tetren)NCR]3+ (R=Me,Ph and p-MeOC6 H4) and the synthesis and kinetics of formation of the tetrazolato complexes [Co(tetren)N4R]2+ (R=Me and Ph; tetren=1,11-diamino-3,6,9-triazaundecane) by reaction with azide ion

The N-bonded nitrile complexes -[Co(tetren)NCR]³⁺ (R=Me, Ph, p-MeOC₆ H₄) have been prepared by the reaction of -[Co(tetren)OH₂]³⁺ with the corresponding nitrile. The kinetics of base hydrolysis have been studied by pH-stat methods. The reactions involve an SN₁CB displacement of the nitrile to give the hydroxopentamine; nucleophilic attack at the nitrile carbon to give the corresponding carboxamido complex does not occur. NaN₃ reacts with the nitrile complexes in slightly acidic solution (pH ca. 5.7) to give the tetrazolato complexes [Co(tetren)N₄ R]²⁺ (R=Me, Ph) which have been characterised. The reaction of azide ion with -[Co(tetren)NCMe]³⁺ has been studied kinetically. The reaction is biphasic involving the initial rapid formation of the N₁-bonded (5-methyltetrazolato) pentaminecobalt(III) complex with k=2×10^–2dm³ mol^–1s^–1 at 25°C followed by the slow isomerisation to the N₂-bonded complex with k=3.5×10^–5s^–1 at pH 5.7.     

The preparation of copper(II) and copper(I) salts in acetonitrile using group VA and VB pentafluorides

Copper(II) fluorine reacts with the pentafluorides, TaF₅, PF₅, and AsF₅, in acetonitrile to give solvated Cu^II, hexafluoroanion salts. These react with copper metal to give the corresponding Cu^I compounds. Similar reactions occur between AsF₅ and silver(I) or thallium(I) fluorides, but silver(II) fluoride reacts with MeCN, and Ag^I hexafluoroarsenate is formed. PF₅ oxidises Cu slowly in MeCN to give Cu^I hexafluorophosphate, but AsF₅ has no oxidising ability towards metals in MeCN. Spectroscopic data for Cu(MF₆)₂·5MeCN and Cu(MF₆)·4MeCN (M = Ta or P) are discussed.     

Ethylene tetramerization: a new route to produce 1-octene in exceptionally high selectivities

Linear alpha-olefins, such as 1-hexene and 1-octene, are important comonomers in the production of linear low-density polyethylene (LLDPE). The conventional method of producing 1-hexene and 1-octene is by oligomerization of ethylene, which yields a wide spectrum of linear alpha-olefins (LAOs). While there exists several processes for producing 1-hexene via ethylene trimerization, a similar route for the selective production of 1-octene has so far been elusive. We now, for the first time, report an unprecedented ethylene tetramerization reaction that produces 1-octene in selectivities exceeding 70%, using an aluminoxane-activated chromium/((R2)2P)2NR1 catalyst system.     

Macrocyclic copper(II) and zinc(II) complexes incorporating phosphate esters

Slow evaporation of solutions prepared by adding either Cu(ClO(4))(2).6H(2)O or Zn(ClO(4))(2).6H(2)O to solutions containing appropriate proportions of Me(3)tacn (1,4,7-trimethyl-1,4,7-triazacyclononane) and sodium phenyl phosphate (Na(2)PhOPO(3)) gave dark blue crystals of [Cu(3)(Me(3)tacn)(3)(PhOPO(3))(2)](ClO(4))(2).(1)/(2)H(2)O (1) and colorless crystals of [Zn(2)(Me(3)tacn)(2)(H(2)O)(4)(PhOPO(3))](ClO(4))(2).H(2)O (2), respectively. Blue crystals of [Cu(tacn)(2)](BNPP)(2) (3) formed in an aqueous solution of [Cu(tacn)Cl(2)], bis(p-nitrophenyl phosphate) (BNPP), and HEPES buffer (pH 7.4). Compound 1 crystallizes in the triclinic space group P1 (No. 2) with a = 9.8053(2) A, b = 12.9068(2) A, c = 22.1132(2) A, alpha = 98.636(1) degrees, beta = 99.546(1) degrees, gamma = 101.1733(8) degrees, and Z = 2 and exhibits trinuclear Cu(II) clusters in which square pyramidal metal centers are capped by two phosphate esters located above and below the plane of the metal centers. The trinuclear cluster is asymmetric having Cu...Cu distances of 4.14, 4.55, and 5.04 A. Compound 2 crystallizes in the monoclinic space group P2(1)/c (No. 14) with a = 13.6248(2) A, b = 11.6002(2) A, c = 25.9681(4) A, beta = 102.0072(9) degrees, and Z = 4 and contains a dinuclear Zn(II) complex formed by linking two units of [Zn(Me(3)tacn)(OH(2))(2)](2+) by a single phosphate ester. Compound 3 crystallizes in the monoclinic space group C2/c (No. 15) with a = 24.7105(5) A, b = 12.8627(3) A, c = 14.0079(3) A, beta = 106.600(1) degrees, and Z = 4 and consists of mononuclear [Cu(tacn)(2)](2+) cations whose charge is balanced by the BNPP(-) anions.     

The effect of triethylenetetraamine (Trien) on the ion flotation of Cu(2+) and Ni(2+)

Ion flotation is a separation process involving the adsorption of a surfactant and counterions at an air/aqueous solution interface. It shows promise for removing toxic heavy metal ions from dilute aqueous solutions. Here we report the effect of a neutral chelating ligand, triethylenetetraamine (Trien), on the ion flotation of cations with dodecylsulfate, DS(-), introduced as sodium dodecylsulfate, SDS. Ion flotation in the aqueous SD-Cu(II)-Ca(II)-Trien system gave strongly preferential removal of Cu(II) over Ca(II), which is a reversal of the order of selectivity seen in the SDS-Cu(II)-Ca(II) system containing no Trien. The removal rates of Cu(2+) and Ni(2+) with DS(-) were much faster in the presence of Trien than for simple aquo ions, and the final metal concentration was significantly lower. Surface tension measurements showed that Trien enhanced the surface activity and adsorption density for SDS-Cu(II) and SDS-Ni(II) solutions. The overall change in the Gibbs free energy for adsorption resulting from complexation was -3.60 kJ/mol for Cu(II) and -3.50 kJ/mol for Ni(II). This included the effects of hydrophobic interactions between the metal-Trien complexes at the air/solution interface, along with changes in the amount of dehydration associated with cosorption of the metal-Trien complex with DS(-) at the air/solution interface.