Unexpected Trends in the Stability and Dissociation Kinetics of Lanthanide(III) Complexes with Cyclen-Based Ligands across the Lanthanide Series.

We report a detailed study of the thermodynamic stability and dissociation kinetics of lanthanide complexes with two ligands containing a cyclen unit, a methyl group, a picolinate arm, and two acetate pendant arms linked to two nitrogen atoms of the macrocycle in either cis (1,4-HDO2APA) or trans (1,7-HDO2APA) positions. The stability constants of the Gd complexes with these two ligands are very similar, with log values of 16.98 and 16.33 for the complexes of 1,4-HDO2APA and 1,7-HDO2APA, respectively. The stability constants of complexes with 1,4-HDO2APA follow the usual trend, increasing from log = 15.96 to log = 19.21. However, the stability of [Ln(1,7-DO2APA)] complexes decreases from log = 16.33 for Gd to 14.24 for Lu. The acid-catalyzed dissociation rates of the Gd complexes differ by a factor of ∼15, with rate constants () of 1.42 and 23.5 M s for [Gd(1,4-DO2APA)] and [Gd(1,7-DO2APA)], respectively. This difference is magnified across the lanthanide series to reach a 5 orders of magnitude higher for [Yb(1,7-DO2APA)] (1475 M s) than for [Yb(1,4-DO2APA)] (5.79 × 10 M s). The acid-catalyzed mechanism involves the protonation of a carboxylate group, followed by a cascade of proton-transfer events that result in the protonation of a nitrogen atom of the cyclen unit. Density functional theory calculations suggest a correlation between the strength of the Ln-O bonds and the kinetic inertness of the complex, with stronger bonds providing more inert complexes. The H NMR resonance of the coordinated water molecule in the [Yb(1,7-DO2APA)] complex at 176 ppm provides a sizable chemical exchange saturation transfer effect thanks to a slow water exchange rate of (15.9 ± 1.6) × 10 s.