Bismuth coordination chemistry: a brief retrospective spanning crystallography to clinical potential

A fresh look back at the chemistry of Bi3+ spanning solid state structural studies, aqueous biphasic separations, and a chromatographic purification of Bi-213 in support of its clinical use in targeted radiotherapy reveals the foundational importance of coordination chemistry and understanding the preferences exhibited by both the metal center and the ligand(s). Select structural studies of the nitrate and halide salts of Bi3+ complexes with the cyclic crown ethers and acyclic polyethylene glycols (PEGs) are reviewed, and the structure of [BiCl3(cis-anti-cis-dicyclohexano-18-crown-6)] is reported and compared to related structures. Liquid/liquid distribution studies emphasizing Bi3+ partitioning in PEG-based aqueous biphasic systems are presented and show that the distribution ratios using halide anions as extractants increase in the expected order: F- < Cl- < Br- < I-. Building on an understanding of the Bi-directed coordination chemistry in halide containing systems, the rationale for a chromatographic purification of Bi-213 is discussed, as are the performance data showing a 96% recovery of chemically and radionuclidically pure Bi-213 in just 0.25 mL of a strip solution that is directly compatible with binding to carboxylate-based biolocalization agents. The importance of coordination chemistry and an interdisciplinary scientific approach are highlighted, as are select future opportunities in targeted radiotherapy.

Automated summary

This study provides a comprehensive investigation into the chemistry of Bi3+, covering solid state structural studies, aqueous biphasic separations, and chromatographic purification of Bi-213 for targeted radiotherapy. The importance of coordination chemistry and the understanding of metal-ligand interactions were highlighted, along with the future opportunities in targeted radiotherapy. The results demonstrate the distribution of Bi3+ in PEG-based aqueous biphasic systems and the successful purification of Bi-213, showcasing a 96% recovery rate of pure Bi-213 in a small volume strip solution compatible with carboxylate-based biolocalization agents.