Metal-ligand bonding in bispidine chelate complexes for radiopharmaceutical applications

The complexes of selected radionuclides relevant for nuclear medicine (In-III, Bi-III, Lu-III, Ac-III and in addition La-III for comparative purposes) with the octadentate (6,6 '-((9-hydroxy-1,5-bis(methoxycarbonyl)-2,4-di(pyridin-2-yl)-3,7-diazabicyclo[3.3.1]nonane-3,7-diyl)bis(methylene))dipicolinic acid) ligand, H(2)bispa(2), have been studied by density functional theory calculations modelling both isolated and aqueous solution conditions. The properties in focus are the encapsulation efficiency of the ligand for the different-size metals (M), the differences in bonding with the various M-III ions analysed using Bader's atoms in molecules theory and the possibility and characteristics of nona- and decacoordination by H2O ligands. The computed results confirmed strong steric effects in the case of the In complex excluding higher than octacoordination. The studied properties depend strongly on the interplay of the sizes and electronic structures of the M-III ions. The computations support high stability of the complexes in aqueous solution, where also the solvation energies of the M-III ions (as dissociation products) play a significant role.