Partial atomic charge of the ion in Gd complexes with acidic ligands can predict complex stability.

The structures of various complexes of Gd with DOTA-based ligands were resolved with molecular dynamics simulation. Gd-ligand complex binding energies, obtained with electronic structure calculations, agree with experimental stability constants. The partial atomic charge of the Gd ion, using the CM5 charge model, can predict the stability of Gd-ligand complexes. [Display omitted] Complexes of gadolinium (Gd) with dodecane tetraacetic acid (DOTA) are widely used as contrasting agents in magnetic resonance imaging. However, concerns over potential toxicity to humans due to the possible unbinding of the Gd ion from the ligand has inspired research efforts into developing more stable Gd3+ chelating agents. Using molecular dynamics simulations and electronic structure calculations, we investigated the structural factors influencing the stability of Gd complexes with DOTA and DOTA-based ligands. The calculated relative binding energies, derived from all-electron single-point energy calculations, showed a strong correlation with experimental stability constants, validating the predictive ability of our computational protocol. A partial atomic charge model that considers both electrostatics and molecular polarity (CM5) showed a very strong correlation between the partial charge of the Gd ion in the complexes with experimentally measured stability constants and computationally derived binding energies, providing a simple yet effective descriptor of stability for Gd-DOTA and related complexes. [ABSTRACT FROM AUTHOR]