Pyridine‐Based Lanthanide Complexes Combining MRI and NIR Luminescence Activities

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.

Lanthanide Complexes with Heteroditopic Ligands as Fluorescent Zinc Sensors

“…The apparent maxima of the spectrum of both complexes is at approximately 30800 cm -1 (325 nm), which is consistent with the singlet-state energies of other pyridine-containing complexes. [29] The addition of Zn [30] For instance, it has been shown that the nature and polarizability of the group occupying a position on or close to the principal axis of the complex affects the relative intensity of the 5 D 0 Ǟ 7 F 2 transition. [31] The more polarizable the axial donor atom is, the greater the relative The hydration states of the EuL1 and EuL2 complexes were studied by comparison of their luminescence lifetimes in H 2 O and D 2 O.…”

Designing Artificial 3D Helicates: Unprecedented Self‐Assembly of Homo‐octanuclear Tetrapods with Europium

“…In addition, accommodating different metal ions within the same molecule can be exploited, fore xample, in magnetic [7] and/or opticald evices [8] and in multimodala gents for biomedical imaging, [9,10] but their controlled preparation remains challenging, especially in the case of 4f heteronuclear systems. [11, 12] Recently,s everalt etranuclear tetrahedral complexes built with lanthanides have been investigated.…”

Metal Complexes as MRI Contrast Enhancement Agents

“…These include, among others, hydroxypyridinonate [39][40][41][42] , AZTA 43 , and DTTA derivatives 44 as well as pyridine-based amino carboxylate ligands. 45 The Gd-H distance, r GdH , which enters at the inverse sixth power into the expression of inner-sphere relaxivity, is a difficult parameter to obtain experimentally. It is generally estimated on the basis of Gd-coordinated water oxygen distances, determined by solid-state x-ray analysis.…”