Parametrization of Zirconium for DFTB3/3OB: A Pathway to Study Complex Zr‐Compounds for Biomedical and Material Science Applications

ABSTRACT This work presents the extension of the semi‐empirical density functional tight binding method, DFTB3, to include zirconium for biomedical and material science applications. The parametrization of Zr has been carried out in consistency with already established 3OB parameters including the elements C, H, N, O, S, P, Mg, Zn, Na, K, Ca, F, Cl, Br, and I. Zirconium‐ligand association and reaction energies have been compared with results from quantum chemical calculations obtained at MP2 and DFT (PBE and B3LYP) level of theory, as well as with those from the semi‐empirical methods DFTB2/PTBP and GFN2‐xTB. A structural validation has been carried out on 1,897 compounds reported in the Cambridge Structural Database, revealing an average root mean square deviation comparable to that obtained at semi‐empirical (DFTB2/PTBP and GFN2‐xTB) level of theory and via the novel neural network potential MACE‐MP‐0. To provide a critical validation of the newly derived parameters, the structure of the biomedically relevant Zr‐DFO complex has been evaluated with respect to a DFT (B3LYP) reference calculation. In addition, extensive DFTB3 MD simulations of the two prominent metal‐organic frameworks UiO‐66 and UiO‐67 have been performed. The results demonstrate the applicability of the newly developed parameters for the study of zirconium‐containing metal‐organic frameworks, when compared to experimental measurements, as well as computational approaches.