Equilibrium and NMR studies on Gd^III, Y^III, Cu^IIand Zn^IIcomplexes of various DTPA–N,N″-bis(amide) ligands. Kinetic stabilities of the gadolinium(iii) complexes

Abstract

Three DTPA-derivative ligands, the non-substituted DTPA-bis(amide) (L(0)), the mono-substituted DTPA-bis(n-butylamide) (L(1)) and the di-substituted DTPA-bis[bis(n-butylamide)] (L(2)) were synthesized. The stability constants of their Gd3+ complexes (GdL) have been determined by pH-potentiometry with the use of EDTA or DTPA as competing ligands. The endogenous Cu2+ and Zn2+ ions form ML, MHL and M(2)L species. For the complexes CuL(0) and CuL(1) the dissociation of the amide hydrogens (CuLH(-1)) has also been detected. The stability constants of complexes formed with Gd3+, Cu2+ and Zn2+ increase with an increase in the number of butyl substituents in the order ML(0) < ML(1) < ML(2). NMR studies of the diamagnetic YL(0) show the presence of four diastereomers formed by changing the chirality of the terminal nitrogens of their enantiomers. At 323 K, the enantiomerization process, involving the racemization of central nitrogen, falls into the fast exchange range. By the assignment and interpretation of 1H and 13C NMR spectra, the fractions of the diastereomers were found to be equal at pH = 5.8 for YL(0). The kinetic stabilities of GdL(0), GdL(1) and GdL(2) have been characterized by the rates of the exchange reactions occurring between the complexes and Eu3+, Cu2+ or Zn2+. The rates of reaction with Eu3+ are independent of the [Eu3+] and increase with increasing [H+], indicating the rate determining role of the proton assisted dissociation of complexes. The rates of reaction with Cu2+ and Zn2+ increase with rising metal ion concentration, which shows that the exchange can take place with direct attack of Cu2+ or Zn2+ on the complex, via the formation of a dinuclear intermediate. The rates of the proton, Cu2+ and Zn2+ assisted dissociation of Gd3+ complexes decrease with increasing number of the n-butyl substituents, which is presumably the result of steric hindrance hampering the formation or dissociation of the intermediates. The kinetic stabilities of GdL(0) and GdL(1) at pH = 7.4, [Cu2+] = 1 x 10(-6) M and [Zn(2+)] = 1 x 10(-5) M are similar to that of Gd(DTPA)2-, while the complex GdL2 possesses a much higher kinetic stability.

Thermodynamic stability and kinetic inertness of a Gd–DTPA bisamide complex grafted onto gold nanoparticles

“…This indicated that, when DTDTPA:Gd is grafted onto the Au nanoparticle, its transmetallation tends to be reduced. This behavior was also reported in a bisamide DTPA series for which the amide hydrogen atoms were gradually substituted with butyl groups, which induced a steric hindrance at the vicinity of the Gd center . The similar result obtained here suggested that the bulky nanoparticle rigidified the structure of the complex and prevented grafted DTDTPA:Gd complexes from extensive demetallation.…”

Synthesis of 64Cu-Labeled Magnetic Nanoparticles for Multimodal Imaging

“…In our polystyrene system, this surface-bound 64 Cu was easily removed by chromatography. The stability constants for DTPA or DOTA complexes with copper are similar, 21.5 and 22.25, respectively (25,41), but slightly higher for DOTA. It is possible for the polystyrene bead system that the large number of amine groups at the particle surface presented a competition binding site for the Cu 2+ ; if the metal was not preinserted into the chelator before conjugation to the nanoparticle surface, then the Cu 2+ bound to the surface of the nanoparticle rather than the DOTA and could be removed by chromatography.…”

Synthesis and Characterization of GaIII, InIII and LuIII Complexes of a Set of dtpa Bis‐Amide Ligands

“…dtpa amides are able to bind a variety of metal ions, ranging from lanthanides11,13–18 and d elements19–22 to alkaline‐earth metals,23 pnictogens24 as well as elements of the boron group 19,24–32. Among this last group, Ga III is of particular interest due to its radioactive isotope 68 Ga, which is commonly used in positron emission tomography (PET).…”