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

Abstract

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.