Predicting the Thermodynamic Stability of Zirconium Radiotracers

The thermodynamic stability of a metal–ligand complex, as measured by the formation constant (log β), is one of the most important parameters that determines metal ion selectivity and potential applications in, for example, radiopharmaceutical science. The stable coordination chemistry of radioactive 89Zr4+ in an aqueous environment is of paramount importance when developing positron-emitting radiotracers based on proteins (usually antibodies) for use with positron emission tomography. Desferrioxamine B (DFO) remains the chelate of choice for clinical applications of 89Zr-labeled proteins, but the coordination of DFO to Zr4+ ions is suboptimal. Many alternative ligands have been reported, but the challenges in measuring very high log β values with metal ions such as Zr4+ that tend to hydrolyze mean that accurate thermodynamic data are scarce. In this work, density functional theory (DFT) calculations were used to predict the reaction energetics for metal ion complexation. Computed values of pseudoformatio...