The vast majority -if not all-of theoretical work to date, addressing the coordination chemistry of Zirconium and potential chelators has been informed by DFT-based electronic structure calculations. While this approach provides a more accurate treatment of the electronic induced forces between the nuclei, thermal effects and the role of solvation are neglected. In this work, we have used classical molecular dynamics simulations of Zr 4+ in water to examine the thermodynamics of the chelating complex for two chelators namely DFO and 4HMS. Our findings paint a more complex scenario than that observed in previous DFT calculations. Specifically, the DFT-optimized structure, in which the three hydroxamate groups of DFO enclose Zr 4+ , is not stable in the MD simulations. Free energy calculations instead show that the most stable Zr 4+ -DFO configuration has only two oxygen atoms from DFO coordinated to the cation. Furthermore, water oxygen atoms have a prominent role in filling the ion's first coordination shell.