To streamline and guide such trial-and-error optimization efforts for chelator design, com-putational methods offer insight into the structure and thermodynamic stability of different chelates under varying conditions mimicking complex biological systems. In this regard, several computational studies have been conducted in order to understand the chelating mechanism of DFO. Specifically, the coordination structure of Zr 4+ with DFO has been discussed as an important parameter in possibly controlling its stability in vivo. Quantum chemistrybased calculations using Density Functional Theory (DFT) for example, have shown that seven or eight-coordinated complexes, with Zr 4+ bound to the six oxygen atoms of DFO and to one or two oxygen atoms from surrounding water molecules, are found to be the most stable complexes. While DFT approaches are more accurate in-so-far as including electronic effects, the vast majority of theoretical studies of DFO and Zr 4+ are conducted at 0K which neglect thermal effects involving fluctuations in the chelator and surrounding solvent molecules.