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

Abstract

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-H₃DO2APA) or trans (1,7-H₃DO2APA) positions. The stability constants of the Gd³⁺ complexes with these two ligands are very similar, with log K_GdL values of 16.98 and 16.33 for the complexes of 1,4-H₃DO2APA and 1,7-H₃DO2APA, respectively. The stability constants of complexes with 1,4-H₃DO2APA follow the usual trend, increasing from log K_LaL = 15.96 to log K_LuL = 19.21. However, the stability of [Ln(1,7-DO2APA)] complexes decreases from log K = 16.33 for Gd³⁺ to 14.24 for Lu³⁺. The acid-catalyzed dissociation rates of the Gd³⁺ complexes differ by a factor of ∼15, with rate constants (k₁) of 1.42 and 23.5 M^-1 s^-1 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 k₁ for [Yb(1,7-DO2APA)] (1475 M^-1 s^-1) than for [Yb(1,4-DO2APA)] (5.79 × 10^-3 M^-1 s^-1). 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_carboxylate bonds and the kinetic inertness of the complex, with stronger bonds providing more inert complexes. The ¹H 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) × 10³ s^-1.