Thermodynamic and Kinetic Study of Scandium(III) Complexes of DTPA and DOTA: A Step Toward Scandium Radiopharmaceuticals |
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| Authors: | Miroslav Pniok Dr Vojtěch Kubí?ek Jana Havlí?ková Dr Jan Kotek Dr Andrea Sabatie‐Gogová Dr Jan Plutnar Prof Sandrine Huclier‐Markai Prof Petr Hermann |
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| Affiliation: | 1. Department of Inorganic Chemistry, Faculty of Science, Universita Karlova v Praze (Charles University in Prague), Hlavova 2030, 12843 Prague 2 (Czech Republic), Fax: ( +420)?22195‐1253;2. CRCNA, UMR 892, INSERM/CNRS/Université de Nantes, 8 quai Moncousu, 44007 Nantes Cedex 1 (France);3. Cyclotron Arronax, 1 Rue Arronax, CS 10112, 44817 Saint‐Herblain Cedex (France);4. Current address: Institute of Organic Chemistry and Biochemistry, Flemingovo náměstí 2, 16610 Prague 6 (Czech Republic);5. Laboratoire Subatech, UMR 6457, Ecole des Mines de Nantes/, CNRS/IN2P3/Université de Nantes, 4 Rue A. Kastler, BP 20722, 44307 Nantes Cedex 3 (France) |
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| Abstract: | 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 45Sc NMR spectroscopic references suitable for aqueous solutions were suggested: 0.1 M Sc(ClO4)3 in 1 M aq. HClO4 (δSc=0.0 ppm), 0.1 M ScCl3 in 1 M aq. HCl (δSc=1.75 ppm) and 0.01 M Sc(ox)4]5? (ox2?=oxalato) in 1 M aq. K2C2O4 (δSc=8.31 ppm). In solution, Sc(dtpa)]2? complex (δSc=83 ppm, ?ν=770 Hz) has a rather symmetric ligand field unlike highly unsymmetrical donor atom arrangement in Sc(dota)]? anion (δSc=100 ppm, ?ν=4300 Hz). The solid‐state structure of K8Sc2(ox)7] ? 13 H2O contains two Sc(ox)3]3? units bridged by twice “side‐on” coordinated oxalate anion with Sc3+ ion in a dodecahedral O8 arrangement. Structures of Sc(dtpa)]2? and Sc(dota)]? in (Hguanidine)]2Sc(dtpa)] ? 3 H2O and KSc(dota)]H6dota]Cl2 ? 4 H2O, 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 (H6dota)2+ units are bridged by a K+ cation. A surprisingly high value of the last DOTA dissociation constant (pKa=12.9) was determined by potentiometry and confirmed by using NMR spectroscopy. Stability constants of scandium(III) complexes (log KScL 27.43 and 30.79 for DTPA and DOTA, respectively) were determined from potentiometric and 45Sc 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 (τ1/2=45 h; 1 M aq. HCl, 25 °C) is much slower than that for Ln(dota)]? complexes. Therefore, DOTA and its derivatives seem to be very suitable ligands for scandium radioisotopes. |
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| Keywords: | ligands NMR spectroscopy radiochemistry radiopharmaceuticals scandium |
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