Browsing by Author "Linder, P W"

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    A computer simulation of the trace metal speciation in seawater
    (1994) Woolard, Christopher Dennis; Linder, P W
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    Computer simulation of metal-ion equilibria in biochemical systems : models for blood plasma
    (1976) May, Peter Michael; Linder, P W
    This thesis describes an investigation, by computer simulation, into the nature of the metal ion binding to low molecular weight ligands in blood plasma. A successful attempt is made to accommodate the effects of metal protein binding on the computed distribution that is obtained. An evaluation of the results is undertaken. The value and some applications of the knowledge arising from this kind of study are examined. The collection, assembly and processing of the data is described. A computer program is written to cope with the very large equilibrium systems that are simulated. The experimentally determined values for the formation constants of the metal ion ligand complexing reactions in the biofluid are found in the literature. These are corrected whenever they are not applicable to physiological conditions of temperature and ionic strength. Where no experimental values were available, formation constants for complexes that seemed likely to be important were estimated using certain types of chemical trend. The results of the blood plasma model may be summarized as follows. Copper and ferric iron are found to exist exclusively as ternary complexes except that the copper dihistidinato complex is important. With copper, these ternary complexes always involve histidine whilst citrate plays an analogous role in the ferric complex formation. Calcium, magnesium and manganese do not appear to exist as ternary complexes. With these three cations the bicarbonate species predominate although the binding is weak; as a consequence of the relatively high ligand concentration in plasma. Zinc and lead form both binary and ternary complexes. The ternary zinc cysteinate citrate complex is found to account for a significant percentage of the low molecular weight complex fraction of this metal. This result is in contrast to those of previous models.
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    Metal complexes of penicillin and cephalosporin antibiotics
    (1975) Jackson, Graham Ellis; Nassimbeni, Luigi R; Linder, P W; Fazakerley, G V
    The interaction between metal-ions and the penicillin and cephalosporin antibiotics have been studied in an attempt to determine both the site and mechanism of this interaction. The solution conformation of the Cu(II) and Mn(II) complexes were determined using an n.m.r, line broadening, technique. The ligands benzylpenicillin, 6-aminopenicillanic acid, cephalothin, cephalexin, ampicillin and thiaproline were used to study the effect of structural changes in the ligand on the structure of the complex. The stability constants of several metal-ions/penicillin complexes were determined potentiometrically. These were correlated with stability constants determined for several related complexes. Finally the kinetics of the Ni(II) substitution reaction with benzylpenicillin, penicilloic acid, ampicillin and thiaproline was studied.
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    Solution equilibria of the methyldopacopper (II) system and the crystal and molecular structures of selected compounds
    (1979) Wright, Martin Robert William; Linder, P W; Nassimbeni, Luigi R
    The contents of this thesis are essentially in two parts. The first deals with solution studies relating to the methyldopa-copper(II) system and its relevance to medicinal chemistry, a full abstract of which is given on page 1 of the main text. The second part describes five single crystal x-ray investigations into some interesting compounds isolated at this university. The abstracts to these topics may be found preceding the relevant sections as they appear in the text on pages 94, 118 and 146, respectively.
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    Syntheses of selected mono- and di-esters of phosphoric acid and stability constants of their copper (II) complexes
    (1984) Armstrong, Moira Margaret; Modro, Tomasz A; Linder, P W; Torrington, R G
    A number of different routes were attempted to the syntheses of organic phosphate models (R₁O)(R₂O)PO; where R₁ = 4-nitrophenyl group and R₂ = benzyl, 2-pyridylmethyl, 1-naphthylor 8-quinolyl group. However, preparative difficulties and side reactions, due mainly to the susceptibility of the 4-nitrophenoxy moiety to nucleophilic displacement reactions, resulted in simplification of the target models to a pair of monoesters (R₃O)PO₃H₂ and a pair of diesters (R₃O)(R₄O)P(O)O⁻Na⁺ where R₃ = 1-naphthyl group (monoester (A) or diester (C)) or 8-quinolyl group (monoester (B) or diester (D)) and R₄ = methyl group. Such a set of substrates allowed comparison of the reactivities of phosphate monoesters and diesters and as the components of each pair differed only by the presence or absence of a tertiary amine function in one of the ester linkages, the effect on the reactivity of such a compound, due to the presence of a heterocyclic atom, could be gauged. Complex formation between ligands (A), (B), (C) and (D) and copper(II) ions in aqueous solution at 25° C and I = 0,15 mol dm⁻³ (Na)[Cl⁻] was investigated by means of glass electrode potentiometry and computational analysis. Mononuclear and hydroxo complexes were found to occur with ligands (A), (B) and (D). No complexation was detected with ligand (C). The copper(II) ion was found to be only singly coordinated to ligands (A) and (D) through a terminal phosphate group and the quinolyl nitrogen respectively,while with ligand (B) a chelate structure was formed involving the quinolyl nitrogen and a terminal phosphate group to form a seven-membered ring. Formation constants are given for two protonation and four copper(II) complexes of ligand (B) and for one protonation and four copper(II) complexes, each, of ligands (A) and (D).