Accueil > Publications > Recherche par années > Années 2010 > 2012

Bonnet, CS, Buron, F, Caillé, F, Shade, CM, Drahoš, B, Pellegatti, L, Zhang, J, Villette, S, Helm, L, Pichon, C, Suzenet, F, Petoud, S. & Tóth E.

Pyridine-Based Lanthanide Complexes Combining MRI and NIR Luminescence Activities

Chemistry - a european journal 18 (5) 1419-1431

par Frapart - publié le , mis à jour le

Abstract :

A series of novel triazole derivative pyridine-based polyamino-polycarboxylate ligands has been synthesized for lanthanide complexation. This versatile platform of chelating agents combines advantageous properties for both magnetic resonance (MR) and optical imaging applications of the corresponding Gd(3+) and near-infrared luminescent lanthanide complexes. The thermodynamic stability constants of the Ln(3+) complexes, as assessed by pH potentiometric measurements, are in the range log K(LnL) =17-19, with a high selectivity for lanthanides over Ca(2+) , Cu(2+) , and Zn(2+) . The complexes are bishydrated, an important advantage to obtain high relaxivities for the Gd(3+) chelates. The water exchange of the Gd(3+) complexes (k(ex) (298) =7.7-9.3×10(6)  s(-1) ) is faster than that of clinically used magnetic resonance imaging (MRI) contrast agents and proceeds through a dissociatively activated mechanism, as evidenced by the positive activation volumes (ΔV(≠) =7.2-8.8 cm(3) mol(-1) ). The new triazole ligands allow a considerable shift towards lower excitation energies of the luminescent lanthanide complexes as compared to the parent pyridinic complex, which is a significant advantage in the perspective of biological applications. In addition, they provide increased epsilon values resulting in a larger number of emitted photons and better detection sensitivity. The most conjugated system PheTPy, bearing a phenyl-triazole pendant on the pyridine ring, is particularly promising as it displays the lowest excitation and triplet-state energies associated with good quantum yields for both Nd(3+) and Yb(3+) complexes. Cellular and in vivo toxicity studies in mice evidenced the non-toxicity and the safe use of such bishydrated complexes in animal experiments. Overall, these pyridinic ligands constitute a highly versatile platform for the simultaneous optimization of both MRI and optical properties of the Gd(3+) and the luminescent lanthanide complexes, respectively.