Stabilities of Ac 3+ Complexes Relevant as Radiopharmaceuticals

High Resolution Image Download MS PowerPoint Slide We present a detailed density functional theory (DFT) investigation of the structural features and thermodynamic stabilities of La 3+ and Ac 3+ complexes relevant to develop radiopharmaceutical agents. A total of 16 chelators were considered, covering the acyclic and macrocyclic families functionalized with different numbers and types of donor atoms. The bond distances of the Ac 3+ coordination environment are systematically longer than those obtained for the La 3+ analogues, which allowed us to estimate an ionic radius for Ac 3+ in coordination number 9 of 1.275 ± 0.020 Å (1.216 and 1.206 Å were proposed for La 3+ ). Energy decomposition analysis (EDA) provided hints into the nature of the metal–ligand interactions and their relative weight in La 3+ and Ac 3+ complexes. A thermodynamic DFT study allowed us to estimate the stability constants of the Ac 3+ complexes from those of the La 3+ ones, as for the latter experimental values are available in the literature. These studies evidenced that Ac 3+ tends to form complexes with lower thermodynamic stability in comparison with La 3+, with the exception of one of the leading chelators for Ac 3+, MACROPA 2–, and the unexpected case of OCTAPA 4– . Overall, the methodology reported here will allow identifying chelators well suited for Ac 3+ coordination, thereby aiding the design of radiopharmaceuticals based on [ 225 Ac]Ac 3+ for targeted α therapy (TAT).