Pyridine-based lanthanide complexes combining MRI and NIR luminescence activities.
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.
Centre de Biophysique Moléculaire, CNRS, rue Charles Sadron, 45071 Orléans, France.
Célia S
CS
Bonnet
Frédéric
F
Buron
Fabien
F
Caillé
Chad M
CM
Shade
Bohuslav
B
Drahoš
Laurent
L
Pellegatti
Jian
J
Zhang
Sandrine
S
Villette
Lothar
L
Helm
Chantal
C
Pichon
Franck
F
Suzenet
Stéphane
S
Petoud
Éva
É
Tóth
D000579:Amidinotransferases; D000818:Animals; D006367:HeLa Cells; D006801:Humans; D028581:Lanthanoid Series Elements / Q000737:chemistry*; D008024:Ligands; D008099:Liver / Q000201:enzymology; D049449:Luminescence; D008279:Magnetic Resonance Imaging / Q000379:methods; D051379:Mice; D008956:Models, Chemical; D015394:Molecular Structure; D009942:Organometallic Compounds / Q000737:chemistry*; D011725:Pyridines / Q000737:chemistry*; D019265:Spectroscopy, Near-Infrared / Q000379:methods; D013696:Temperature; D014230:Triazoles / Q000737:chemistry
D028581:Lanthanoid Series Elements; D008024:Ligands; D009942:Organometallic Compounds; D011725:Pyridines; D014230:Triazoles; D000579:Amidinotransferases