Dissemin is shutting down on January 1st, 2025

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Wiley, Chemistry - A European Journal, 3(22), p. 896-901, 2016

DOI: 10.1002/chem.201503836

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Approaching the Kinetic Inertness of Macrocyclic Gadolinium(III)-Based MRI Contrast Agents with Highly Rigid Open-Chain Derivatives

This paper is available in a repository.
This paper is available in a repository.

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Abstract

A highly rigid open-chain octadentate ligand (H4cddadpa), containing a diaminecyclohexane unit to replace the ethylenediamine bridge of 6,6'-((ethane-1,2 diylbis((carboxymethyl)azanediyl))bis(methylene))dipicolinic acid (H4octapa), was synthesized. This structural modification slightly improves the thermodynamic stability of the Gd3+ complex (logKGdL = 20.68 vs 20.23 for [Gd(octapa)]-), while other MRI-relevant parameters remain practically unaffected (number of coordinated water molecules, q=1; relaxivity, r1 =5.73 mM-1s-1 at 20 MHz and 295 K). Most remarkably, the kinetic inertness of the complex is improved to a great extent by the rigidifying effect of the diaminecyclohexane unit in the ligand skeleton: the half-live of dissociation calculated for physiological conditions is 6 orders of magnitude higher for [Gd(cddadpa)]- (t1/2=1.49x105 h) than for [Gd(octapa)]-. As compared to non-macrocyclic MRI contrast agents approved for clinical use ([Gd(dtpa-bma)], [Gd(dtpa-bmea)], [Gd(dtpa)]2- and [Gd(bopta)]2-), the kinetic inertness of this novel chelate is superior by 2-3 orders of magnitude, and it is the highest among all linear Gd3+ chelates known so far.