Chemistry of Gallium

Gallium is a group 13 element and exists most commonly in the +3 oxidation state. While lower oxidation states have been observed, all relevant radiopharma-ceuticals occur in this oxidation state. Similar to other group 13 elements (B, Al, and In), Ga3+ is classified as a "hard acid", bonding strongly to highly ionic, non-po-larizable Lewis bases. As a result, gallium chemistry is dominated by ligands containing oxygen and nitrogen donor atoms [36]. There are two requirements for using gallium complexes as radiopharmaceuticals. The first is that gallium complexes must resist hydrolysis at physiological pH. Ga(OH)3, the primary product formed at physiological pH, is insoluble. It is not until the pH is increased above 9.6 that the soluble species [Ga(OH)4]- is formed. The second concern is that Ga3+ has an electronic configuration of 3d10, and this is similar to that of high spin Fe3+, which has a half-filled 3d shell. As a result, their ionic radii, ionization potential, and coordination environment are similar. Thus, gallium radiopharmaceuticals must be stable enough to avoid trans-chelation of Ga3+ to various iron-binding proteins, particularly transferrin. Transferrin has two binding sites, for which the gallium binding constants are 20.3 and 19.3 [37]. In practice, these requirements necessitate the coordination of Ga3+ by a polydentate ligand, typically forming gallium species that are six-coordinate. However, several Ga(III) complexes with coordination numbers four or five are stable in vivo.

0 0

Post a comment