Synthesis and Structural Characterization of Complexes of a DO3A-Conjugated Triphenylphosphonium Cation with Diagnostically Important Metal Ions

To understand the coordination chemistry of a DO3A-conjugated triphenylphosphonium (TPP) cation, triphenyl(4-((4,7,10-tris(carboxymethyl)-1,4,7,10-tetraazacyclododecan-1-yl)methyl)benzyl)phosphonium (DO3A-xy-TPP), with
diagnostically important metal ions, In(DO3A-xy-TPP)+, Ga(DO3A-xy-TPP)+, and Mn(DO3A-xy-TPP) were prepared
by reacting DO3A-xy-TPP with 1 equiv of the respective metal salt. All three complexes have been characterized
by elemental analysis, IR, ESI-MS, NMR methods (for In(DO3A-xy-TPP)+ and Ga(DO3A-xy-TPP)+), and X-ray
crystallography. Results from HPLC concordance experiments show that 111In(DO3A-xy-TPP)+ and In(DO3A-xy-TPP)+ have the same composition. The solid-state structures of In(DO3A-xy-TPP)+ and Mn(DO3A-xy-TPP) are
very similar with DO3A being heptadentate in bonding to In(III) and Mn(II) in a monocapped octahedral coordination
geometry. Because of the smaller size of Ga(III), the DO3A in Ga(DO3A-xy-TPP)+ is only hexadentate with four
amine-N and two carboxylate-O atoms bonding to Ga(III). One carboxylic acid group in DO3A is deprotonated to
balance the positive charge of Ga(III). The coordination geometry of Ga(DO3A-xy-TPP)+ is best described as a
distorted octahedron. The NMR data shows that the coordinated DO3A in In(DO3A-xy-TPP)+ and Ga(DO3A-xy-TPP)+ is symmetrical in aqueous solution. There is no dissociation of the acetate chelating arms in In(DO3A-xy-TPP)+ and Ga(DO3A-xy-TPP)+, providing indirect evidence for the high solution stability of 111In(DO3A-xy-TPP)+
and 68Ga(DO3A-xy-TPP)+.