Studies on the kinetic stabilities of the Gd3+ complexes formed with the N-mono(methylamide), N′-mono(methylamide) and N,N″-bis(methylamide) derivatives of diethylenetriamine-N,N,N′,N″,N″-pentaacetic acid

Lajos Sarka, László Burai, Róbert Király, László Zékány, Ernõ Brücher

Research output: Contribution to journalArticle

40 Citations (Scopus)

Abstract

High kinetic stability is an important requirement for the Gd3+ complexes used as contrast enhancement agents in magnetic resonance imaging. The kinetic stabilities of the Gd3+ complexes formed with DTPA-N-mono(methylamide) (L3), DTPA-N′-mono(methylamide) (L2) and DTPA-bis(methylamide) (L1) are characterized by the rates of the exchange reactions with Eu3+ and the endogenous Cu2+ and Zn2+. The exchange reactions occur via the proton-assisted dissociation of the complexes and direct attack of the exchanging metal ions on the complex. On the basis of the line-shape analysis of the 1H NMR spectra of the LaL2, obtained in the pH range 2.5-3.5, we assume that for the proton-assisted dissociation of the complexes the formation of an intermediate containing a free iminodiacetate group must be followed with the rupture of the metal-central nitrogen bond. At about pH≥5, the reactions between GdL2 or GdL3 and Cu2+ or Zn2+ proceed predominantly by direct reaction of the reactants, through the formation of dinuclear intermediates. The contribution of the proton-assisted dissociation is highly important for GdL1, but its reaction with Zn2+ is significantly slower than the reactions of GdL2 and GdL3. The overall rates of dissociation of GdL1, GdL2, GdL3 and Gd(DTPA)2- through H+ (pH 7.4), Cu2+ (1×10-6 M) and Zn2+ (1×10-5 M)-assisted reactions are surprisingly very similar. Replacement of one or two carboxylates with amide groups results in significantly decreased stability constants, but has practically no effect on the kinetic stability of the Gd3+ complexes, indicating the lower reactivity of the amide groups with Cu2+ and Zn2+.

Original languageEnglish
Pages (from-to)320-326
Number of pages7
JournalJournal of Inorganic Biochemistry
Volume91
Issue number1
DOIs
Publication statusPublished - Jul 25 2002

Keywords

  • Contrast agents
  • Exchange reactions
  • Gd-chelates
  • Kinetics

ASJC Scopus subject areas

  • Biochemistry
  • Inorganic Chemistry

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