Structural, stability and relaxation features of lanthanide‐complexes designed for multimodal imaging detection of enzyme activities

Lanthanide complexes of DO3A-derivative ligands bearing a pyridine-carbamate or pyridine-amine pendant have potential interest in the design of enzymatically activated imaging probes. They are stable and inert, with an exceptionally high kinetic inertness for the carbamate analogue (estimated dissociation half-life ~10⁸ h at pH 7.4).

Abstract

Lanthanide complexes of DO3A-derivative ligands bearing a pyridine-carbamate (L1) or pyridine-amine (L2) arm have potential interest in the design of enzymatically activated imaging probes. Solid-state X-ray structures for CeL1 and YbL2 both demonstrate twisted square antiprismatic geometry, with the metal ion in a nine- or an eight-coordinate environment, respectively. As assessed by pH-potentiometry, in solution lanthanide ions form more stable complexes with the nonadentate L1 than with the octadentate L2 ligand (logK _ML=18.7–21.1 vs. 16.7–18.6, respectively), while stability constants are similar for L1 and L2 chelates of Mg²⁺, Ca²⁺, Zn²⁺ or Cu²⁺. The kinetic inertness of GdL1 is exceptionally high, with an estimated dissociation half-life of ~10⁸ h at pH 7.4, while LnL2 (Ln=Ce, Gd, Yb) complexes have 3–4 orders of magnitude faster dissociation, related to the presence of the protonatable, non-coordinating amine function. The water exchange rate determined for the monohydrated GdL2 (k _ex ²⁹⁸=1.3×10⁶ s⁻¹) shows a threefold decrease with respect to GdDOTA, as a consequence of a reduction in the negative charge and in the steric crowding around the water binding site, both important in dissociatively activated water exchange processes.

Zum Volltext