Computational insights into the redox properties and electronic structures of [Tc=O]3+ complexes: Implications for 99mTc-radiopharmaceuticals

Technetium-99m plays a pivotal role in nuclear medicine, offering unique IMAGING capabilities due to its favorable physical and chemical properties. This study investigates the redox behavior and electronic structures of three representative Tc(V) oxo complexes, [TcO(HMPAO)], [TcO(Bicisate)], and [TcO(DMSA)₂]^-, using computational techniques. Employing relativistic density functional theory with the Zero-Order Regular Approximation (ZORA), we analyze singlet-triplet energy gaps, Gibbs free energy changes, and redox potentials in neutral and acidic environments. The results highlight the significant influence of co-ligands on the electronic stabilization of complexes and their tendencies toward reduction and protonation. The findings also elucidate the role of Jahn-Teller distortions in shaping the redox properties of the studied complexes. Redox potential trends indicate enhanced reducibility in complexes with sulfur-based ligands, impacting their clinical utility. This study provides valuable insights into the design and optimization of technetium-based radiopharmaceuticals, emphasizing their stability and behavior under physiological conditions.