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 (log K ML =18.7–21.1 vs. 16.7–18.6, respectively), while stability constants are similar for L1 and L2 chelates of Mg 2+ , Ca 2+ , Zn 2+ or Cu 2+ . The kinetic inertness of GdL1 is exceptionally high, with an estimated dissociation half‐life of ~10 8 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 =1.3×10 6 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.