Thermodynamic and Kinetic Study of Scandium(III) Complexes of DTPA and DOTA: A Step Toward Scandium Radiopharmaceuticals

Diethylenetriamine-N, N,N',N '',N ''-pentaacetic acid (DTPA) and 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA) scandium(III) complexes were investigated in the solution and solid state. Three Sc-45 NMR spectroscopic references suitable for aqueous solutions were suggested: 0.1 m Sc(ClO4)(3) in 1 m aq. HClO4 (delta(Sc)= 0.0 ppm), 0.1 M ScCl3 in 1 M aq. HCl (delta(Sc)= 1.75 ppm) and 0.01 M [Sc(ox)(4)](5-) (ox(2-) = oxalato) in 1 M aq. K2C2O4 (delta(Sc)= 8.31 ppm). In solution, [Sc-(dtpa)](2-) complex (delta(Sc)= 83 ppm, Delta nu = 770 Hz) has a rather symmetric ligand field unlike highly unsymmetrical donor atom arrangement in [Sc(dota)](-) anion (delta(Sc)= 100 ppm, Delta nu = 4300 Hz). The solid-state structure of K-8[Sc-2(ox)(7)]center dot 13H(2)O contains two [Sc(ox)(3)](3-) units bridged by twice side-on coordinated oxalate anion with Sc3+ ion in a dodecahedral O-8 arrangement. Structures of [Sc(dtpa)](2-) and [Sc(dota)](-) in [(Hguanidine)](2)[Sc(dtpa)]center dot 3H(2)O and K[Sc(dota)][H(6)dota]-Cl-2 center dot 4H(2)O, respectively, are analogous to those of trivalent lanthanide complexes with the same ligands. The [Sc(dota)](-) unit exhibits twisted square-antiprismatic arrangement without an axial ligand (TSA' isomer) and [Sc(dota)](-) and (H(6)dota)(2+) units are bridged by a K+ cation. A surprisingly high value of the last DOTA dissociation constant (pK(a) = 12.9) was determined by potentiometry and confirmed by using NMR spectroscopy. Stability constants of scandium(III) complexes (log K-ScL 27.43 and 30.79 for DTPA and DOTA, respectively) were determined from potentiometric and Sc-45 NMR spectroscopic data. Both complexes are fully formed even below pH 2. Complexation of DOTA with the Sc3+ ion is much faster than with trivalent lanthanides. Proton-assisted decomplexation of the [Sc(dota)](-) complex (tau(1/2) = 45 h; 1 M aq. HCl, 25 degrees C) is much slower than that for [Ln(dota)](-) complexes. Therefore, DOTA and its derivatives seem to be very suitable ligands for scandium radioisotopes.