Gd(3)TCAS(2): An Aquated Gd(3+)-Thiacalix[4]arene Sandwich Cluster with Extremely Slow Ligand Substitution Kinetics

[Image: see text] In aqueous solution, Gd(3+) and thiacalix[4]arene-p-tetrasulfonate (TCAS) form the complex [Gd(3)TCAS(2)](7–), in which a trinuclear Gd(3+) core is sandwiched by two TCAS ligands. Acid-catalyzed dissociation reactions, as well as transmetalation and ligand exchange with physiological concentrations of Zn(2+) and phosphate, showed [Gd(3)TCAS(2)](7–) to be extremely inert compared to other Gd complexes. Luminescence lifetime measurements of the Tb analogue Tb(3)TCAS(2) allowed estimation of the mean hydration number q to be 2.4 per Tb ion. The longitudinal relaxivity of [Gd(3)TCAS(2)](7–) (per Gd(3+)) was r(1) = 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 Gd(3+) 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 [Gd(3)TCAS(2)](7–) can be attributed to the very rigid coordination geometry.