Calorimetric, Spectroscopic, and Model Studies Provide Insight into the Transport of Ti(IV) by Human Serum Transferrin.

Evidence suggests that transferrin can bind Ti(IV) in an unhydrolyzed form (without bound hydroxide or oxide) or in a hydrolyzed form. Ti(IV) coordination by N,N′-di(o-hydroxybenzyl)ethylenediamine-N,N′-diacetic acid (HBED) at different pH values models the two forms of Ti(IV)-loaded transferrin spe...

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Publicado en:Journal of the American Chemical Society Vol. 129; no. 11; pp. 3444 - 3455
Autores principales: Tinoco, Arthur D., Incarvito, Christopher D., Valentine, Ann M.
Formato: Artículo
Publicado: American Chemical Society 3/21/2007
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Acceso en línea:Ver este registro en EBSCOhost
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        atl: Calorimetric, Spectroscopic, and Model Studies Provide Insight into the Transport of Ti(IV) by Human Serum Transferrin.
      aug:
        au:
          Tinoco, Arthur D.
          Incarvito, Christopher D.
          Valentine, Ann M.
        affil: Department of Chemistry, Yale University, P.O. Box 208107, New Haven, Connecticut 06520-8107
      su:
        Transferrin
        Spectroscopic imaging
        Hydroxides
        Carrier proteins
        Hydrolysis
      sug:
        subj:
          Transferrin
          Spectroscopic imaging
          Hydroxides
          Carrier proteins
          Hydrolysis
      ab: Evidence suggests that transferrin can bind Ti(IV) in an unhydrolyzed form (without bound hydroxide or oxide) or in a hydrolyzed form. Ti(IV) coordination by N,N′-di(o-hydroxybenzyl)ethylenediamine-N,N′-diacetic acid (HBED) at different pH values models the two forms of Ti(IV)-loaded transferrin spectrally and structurally. C NMR and stopped-flow kinetic experiments reveal that when the metal is delivered to the protein using an unhydrolyzed source, Ti(IV) can coordinate in the typical distorted octahedral environment with a bound synergistic anion. The crystal structure of TiHBED obtained at low pH models this type of coordination. The solution structure of the complex compares favorably with the solid state from pH 3.0 to 4.0, and the complex can be reduced with E = -641 mV vs NHE. Kinetic and thermodynamic competition studies at pH 3.0 reveal that Ti(citrate)3 reacts with HBED via a dissociative mechanism and that the stability of TiHBED (log β = 34.024) is weaker than that of the Fe(III) complex, pH stability studies show that Ti(IV) hydrolyzes ligand waters at higher pH but still remains bound to HBED until pH 9.5. Similarly, at a pH greater than 8.0 the synergistic anion that binds Ti(IV) in transferrin is readily displaced by irreversible metal hydrolysis although the metal remains bound to the protein until pH 9.5. Thermal denaturation studies conducted optically and by differential scanning calorimetry reveal that Ti(IV)-bound transferrin experiences only minimal enhanced thermal stability unlike when Fe(III) is bound. The C- and N-lobe transition T values shift to a few degrees higher. The stability, competition, and redox studies performed provide insight into the possible mechanism of Ti-Tf transport in cells.
      pubtype: Academic Journal
      doctype: Article
      src: R
    language: English
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