The element astatine shows promising properties to use in targeted cancer radiotherapy. Its isotope At-211 has a half-life of 7.2 hours and undergoes alpha-decay into relatively non-toxic products. It can destroy single malignant cells and get out of the system quickly and with minimal side effects. The major obstacle in developing efficacious astatine-based therapeutic agents is its understudied chemistry leading to the in vivo loss of At-211. Limited availability and a high cost of the At-211 isotope make its experimental explorations problematic. The alternative is to model astatine compounds computationally. We present state-of-the-art models of small astatine molecules (At2, HAt, and AtAu) based on relativistic coupled-cluster and density functional theory to account for intertwined effects of spin-orbit interaction and electronic correlations. The results from the relativistic two component coupled-cluster method were compared to the results of the single component coupled-cluster method with the addition of the spin-orbit contribution from relativistic density functional theory using a variety of functionals. For each molecule, the difference between binding energy of the double component and single component was around one electron volt. However, when the spin-orbit contribution taken from the relativistic density functional theory was added to the result of the single component, it came close to the result of the two component coupled-cluster method. The functional that most closely represented the results of the double component coupled-cluster method when added to the results of the single component coupled-cluster method varied between each of the molecules modeled. Overall, we explored the reliability of density functional models and developed computational protocols applicable to complex molecular entities such as drug precursors to contain At-211 and make its targeted delivery efficient.

Towards predictive <i>ab initio</i> models of astatine compounds

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ACS Fall 2022

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Towards predictive ab initio models of astatine compounds