Exploring Cyclic Aminopolycarboxylate Ligands for Sb(III) Complexation: PCTA and Its Derivatives as a Promising Solution

Abstract

In recent years Auger electron emitters have been suggested as promising candidates for radiotherapy with no side effects in cancer treatment. In this work we report a detailed coordination chemistry study of [Sb(PCTA)] (PCTA: 3,6,9,15-tetraazabicyclo[9.3.1]pentadeca-1(15),11,13-triene-3,6,9-triacetic acid), a macrocyclic aminopolycarboxylate-type complex of antimony(III), whose ¹¹⁹Sb isotope could be a suitable low-energy electron emitter for radiotherapy. The thermodynamic stability of the chelate obtained by pH-potentiometry and UV-vis spectrophotometry is high enough (log K_[Sb(PCTA)] = 23.2(1)) to prevent the hydrolysis of the metal ion near physiological pH. The formation of [Sb(PCTA)] is confirmed by NMR and electrospray ionization mass spectrometry measurements in solution; furthermore, the structure of [Sb(PCTA)]·NaCl·3H₂O and [Sb(PCTA)]·HCl·3H₂O is described by X-ray and density functional theory calculations. Consequently, the [Sb(PCTA)] is the first thermodynamically stable antimony(III) complex bearing polyamino-polycarboxylate macrocyclic platform. Our results demonstrate the potential of rigid (pyclen derivative) ligands as chelators for future applications of Sb(III) in a targeted radiotherapy based on the ¹¹⁹Sb isotope.