Modeling DOTA Decarboxylation in the Context of α-Radiolysis Using DFT Calculations

Aminopolycarboxylic acids such as 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA) are a widely used class of chelating agent, particularly in the nuclear energy field. When exposed to radiological materials, DOTA may undergo radiolytic degradation during use or after disposal, requiring a mechanistic investigation. In this work, the decarboxylation reaction of DOTA in aqueous solution is modeled using density functional theory (DFT) calculations, consistent with reported CO₂ formation during α-radiolysis of aqueous DOTA. Different reactions are proposed and modeled: direct cleavage and radical formation. The first path involves two sequential barriers: an initial low-energy hydroxyl torsion (ΔE = 9.9 kcal mol^-1) followed by an intramolecular hydrogen-transfer-assisted decarboxylation; the latter constitutes the reaction activation barrier (ΔE = 73.3 kcal mol^-1). The second path takes place at a deprotonated carboxyl group, beginning with a radical formation via interaction with OH^• radicals (abundantly produced during water radiolysis) and leading to decarboxylation with a ΔE of only 18.3 kcal mol^-1. Overall, the radical formation (after deprotonation) markedly lowers the effective energetic barrier required for decarboxylation, suggesting it is a preferred pathway for degradation. This result highlights the role of chemical attack by radicals generated during water radiolysis in promoting DOTA degradation, as observed for other radiolytically exposed materials.