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

Abstract

A fresh look back at the chemistry of Bi3+ spanning solid state structural studies, aqueous biphasic separations, and a chromatographic purification of 213 Bi 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 213 Bi is discussed, as are the performance data showing a 96% recovery of chemically and radionuclidically pure 213 Bi 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.