Some new DTPA-N,N″-bis(amides) functionalized by alkyl carboxylates: Synthesis, complexation and stability properties

Sujit Dutta, Suk Kyung Kim, Daksha B. Patel, Tae Jeong Kim, Yongmin Chang

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21 Scopus citations

Abstract

A new series of DTPA-N,N″-bis(amide) ligands functionalized by alkyl carboxylates on the amide side-arms (1a-1l) and their Gd(III) complexes of the type [Gd(1)(H2O)] · xH2O (2a-2l) were synthesized and characterized by analytical and spectroscopic techniques. Potentiality of 2a-2l as contrast agent for magnetic resonance imaging (MRI CA) was investigated by measuring some relevant physicochemical properties such as (i) the protonation constants of 1a-1l, (ii) thermodynamic and conditional stability constants of 2a-2l, (iii) the selectivity (pGd) of 1a-1l for the Gd(III) ion over the endogenous metal ions such as Zn(II), Ca(II), and Cu(II), and (iv) the relaxivities (R1 and R2) of 2a-2l in aqueous and aqueous HP-β-CD solutions. Comparative studies reveal that most of new Gd(III) complexes show enhanced thermodynamic stability and selectivity as compared with those of [Gd(DTPA-BMA)(H2O)] (DTPA-BMA = N,N″-di(methylcarbamoylmethyl)diethylenetriamine-N,N′,N″-triacetate). Also enhanced with 1a-1l (except 1f and 1h) is affinity for Gd(III) as compared with [DTPA-BMA]3- under physiological conditions. The relaxivities (R1 and R2) of aqueous solutions of 2a-2l, on the other hand, drop significantly as compared with [Gd(DTPA-BMA)(H2O)] although they increase dramatically (6-10 fold) in aqueous hydroxypropyl-β-cyclodextrin (HP-β-CD) solutions.

Original languageEnglish
Pages (from-to)3799-3809
Number of pages11
JournalPolyhedron
Volume26
Issue number14
DOIs
StatePublished - 31 Aug 2007

Keywords

  • DTPA-bis(amide) ligands
  • Gadolinium
  • Hydroxypropyl-β-cyclodextrin
  • MRI contrast agents
  • Poly(aminocarboxylate) ligands
  • Thermodynamic stability

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