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Thermodynamic and Kinetic Study of Scandium(III) Complexes of DTPA and DOTA: A Step Toward Scandium Radiopharmaceuticals
Author(s) -
Pniok Miroslav,
Kubíček Vojtěch,
Havlíčková Jana,
Kotek Jan,
SabatieGogová Andrea,
Plutnar Jan,
HuclierMarkai Sandrine,
Hermann Petr
Publication year - 2014
Publication title -
chemistry – a european journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.687
H-Index - 242
eISSN - 1521-3765
pISSN - 0947-6539
DOI - 10.1002/chem.201402041
Subject(s) - dota , scandium , chemistry , lanthanide , dodecahedron , diethylenetriamine , ligand (biochemistry) , oxalate , ethylenediamine , dissociation (chemistry) , crystallography , ion , chelation , stereochemistry , medicinal chemistry , inorganic chemistry , biochemistry , receptor , organic chemistry
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 45 Sc NMR spectroscopic references suitable for aqueous solutions were suggested: 0.1 M Sc(ClO 4 ) 3 in 1 M aq. HClO 4 ( δ Sc =0.0 ppm), 0.1 M ScCl 3 in 1 M aq. HCl ( δ Sc =1.75 ppm) and 0.01 M [Sc(ox) 4 ] 5− (ox 2− =oxalato) in 1 M aq. K 2 C 2 O 4 ( δ Sc =8.31 ppm). In solution, [Sc(dtpa)] 2− complex ( δ Sc =83 ppm, ▵ ν =770 Hz) has a rather symmetric ligand field unlike highly unsymmetrical donor atom arrangement in [Sc(dota)] − anion ( δ Sc =100 ppm, ▵ ν =4300 Hz). The solid‐state structure of K 8 [Sc 2 (ox) 7 ] ⋅ 13 H 2 O contains two [Sc(ox) 3 ] 3− units bridged by twice “side‐on” coordinated oxalate anion with Sc 3+ ion in a dodecahedral O 8 arrangement. Structures of [Sc(dtpa)] 2− and [Sc(dota)] − in [(Hguanidine)] 2 [Sc(dtpa)] ⋅ 3 H 2 O and K[Sc(dota)][H 6 dota]Cl 2 ⋅ 4 H 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 (p K 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 45 Sc NMR spectroscopic data. Both complexes are fully formed even below pH 2. Complexation of DOTA with the Sc 3+ ion is much faster than with trivalent lanthanides. Proton‐assisted decomplexation of the [Sc(dota)] − complex ( τ 1/2 =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.