Complexes of Bifunctional DO3A-N-(?-amino)propinate Ligands with Mg(II), Ca(II), Cu(II), Zn(II), and Lanthanide(III) Ions: Thermodynamic Stability, Formation and Dissociation Kinetics, and Solution Dynamic NMR Studies

The thermodynamic, kinetic, and structural properties of Ln3+ complexes with the bifunctional DO3A-ACE4? ligand its amide derivative DO3A-BACE4? (modelling case where binds to vector molecules) have been studied in order confirm usefulness corresponding Gd3+ as relaxation labels targeted MRI contrast agents. stability constants Mg2+ Ca2+ are lower than for DOTA4? DO3A3?, while Zn2+ Cu2+ similar higher DO3A3? complexes. Ln(DO3A-BACE)? increase from Ce3+ but remain practically constant late ions (represented by Yb3+). Ln(DO3A-ACE)4? Ln(DO3A-BACE)4? several orders magnitude those formation rate Eu(DO3A-ACE)? is one slower Eu(DOTA)?, due presence protonated amine group, which destabilizes intermediate complex. This group causes Ln(DO3A-ACE)? dissociate faster Ln(DOTA)? absence results inertness (as judged acid assisted dissociation). 1H NMR spectra diamagnetic Y(DO3A-ACE)? Y(DO3A-BACE)? reflect slow dynamics at low temperatures intramolecular isomerization process between SA pair enantiomers, R-?(????) S-?(????). conformation C?-substituted pendant arm different two complexes, bulky substituent further away macrocyclic ring amino minimize steric hindrance. temperature dependence reflects motions arms rearrangements both Although losing some thermodynamic relative Gd(DOTA)?, Gd(DO3A-BACE)? still quite inert, indicating design GBCAs Ln3+-based tags protein analysis.