Gd₃TCAS₂: An Aquated Gd³⁺-Thiacalix[4]arene Sandwich Cluster with Extremely Slow Ligand Substitution Kinetics

In aqueous solution, Gd³⁺ and thiacalix[4]­arene-p-tetrasulfonate (TCAS) form the complex [Gd₃TCAS₂]^7–, in which a trinuclear Gd³⁺ core is sandwiched by two TCAS ligands. Acid-catalyzed dissociation reactions, as well as transmetalation and ligand exchange with physiological concentrations of Zn²⁺ and phosphate, showed [Gd₃TCAS₂]^7– to be extremely inert compared to other Gd complexes. Luminescence lifetime measurements of the Tb analogue Tb₃TCAS₂ allowed estimation of the mean hydration number q to be 2.4 per Tb ion. The longitudinal relaxivity of [Gd₃TCAS₂]^7– (per Gd³⁺) was r₁ = 5.83 mM^–1 s^–1 at 20 Hz (37 °C, pH 7.4); however, this relaxivity was limited by an extremely slow water exchange rate that was 5 orders of magnitude slower than the Gd³⁺ aqua ion. Binding to serum albumin resulted in no relaxivity increase owing to the extremely slow water exchange kinetics. The slow dissociation and water exchange kinetics of [Gd₃TCAS₂]^7– can be attributed to the very rigid coordination geometry.