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

Gyula Tircsó (1) , Martín Regueiro-Figueroa (2) , Viktória Nagy (3) , Zoltán Garda (3) , Tamás Garai (3) , Ferenc Krisztián Kálmán (3) , David Esteban-Gómez (2) , Éva Tóth (1) , Carlos Platas-Iglesias (2)

1 CBM - Centre de biophysique moléculaire
2 Departamento de Química Fundamental
3 University of Debrecen Egyetem [Debrecen]

A highly rigid open-chain octadentate ligand (H4 cddadpa) containing a diaminocylohexane unit to replace the ethylenediamine bridge of 6,6'-[(ethane-1,2 diylbis{(carboxymethyl)azanediyl})bis(methylene)]dipicolinic acid (H4 octapa) was synthesized. This structural modification improves the thermodynamic stability of the Gd(3+) complex slightly (log KGdL =20.68 vs. 20.23 for [Gd(octapa)](-) ) while other MRI-relevant parameters remain unaffected (one coordinated water molecule; relaxivity r1 =5.73 mm(-1) s(-1) at 20 MHz and 295 K). Kinetic inertness is improved by the rigidifying effect of the diaminocylohexane unit in the ligand skeleton (half-life of dissociation for physiological conditions is 6 orders of magnitude higher for [Gd(cddadpa)](-) (t1/2 =1.49x10(5) h) than for [Gd(octapa)](-) . The kinetic inertness of this novel chelate is superior by 2-3 orders of magnitude compared to non-macrocyclic MRI contrast agents approved for clinical use.

Domaines: Sciences du Vivant [q-bio]

Gyula Tircsó, Martín Regueiro-Figueroa, Viktória Nagy, Zoltán Garda, Tamás Garai, et al.. Approaching the Kinetic Inertness of Macrocyclic Gadolinium(III)-Based MRI Contrast Agents with Highly Rigid Open-Chain Derivatives. Chemistry - A European Journal, 2016, 22 (3), pp.896 - 901. ⟨10.1002/chem.201503836⟩. ⟨hal-01407817⟩