Shape and Size Tuning of BiIII-Centered Polyoxopalladates: High Resolution 209Bi NMR and 205/206Bi Radiolabeling for Potential Pharmaceutical Applications.

Abstract

We have discovered five bismuth(III)-containing polyoxopalladates (POPs) which were fully characterized by solution and solid-state physicochemical techniques: the cube-shaped [BiPd12O32(AsPh)8]5- (BiPd12AsL), [BiPd12O32(AsC6H4N3)8]5- (BiPd12AsLN), and [BiPd12O32(AsC6H4COO)8]13- (BiPd12AsLC) as well as the star-shaped [BiPd15O40(PO)10H6]11- (BiPd15P) and [BiPd15O40(PPh)10]7- (BiPd15PL), respectively. The organically modified capping groups phenylarsonate, p-azidophenylarsonate, and p-carboxyphenylarsonate were chosen as the azido (-N3) and carboxyl (-COOH) groups open up opportunities to covalently conjugate (via click reaction, amide coupling, etc.) with targeting vectors. The synthesis of p-azidophenylarsonate is reported here for the first time. The effects of the BiIII template and the organoarsonate vs -posphonate capping groups on the resulting POP shape (cube vs star) are discussed. The 209Bi NMR (I = 9/2) spectra of BiPd12AsL, BiPd12AsLN, and BiPd12AsLC revealed narrow peaks (ν1/2 ∼ 200 Hz) at 5470 ppm with a longitudinal relaxation time in the millisecond range (at 8.46 T). The absence of a quadrupolar relaxation contribution could be attributed to the allocation of BiIII in the highly symmetrical cuboid POP host cage. Similar peaks were absent in the 209Bi-NMR spectra of the star-shaped POPs BiPd15P and BiPd15PL due to the less symmetric coordination environment around the central BiIII ion. Further, 205/206Bi-radiolabeled POPs have been synthesized by incorporating a 205/206BiIII ion in the center of the POP structures. Carrier-free 205/206Bi radioisotopes (as surrogates of α-emitting 213Bi) were incorporated into the POP host-cage for the preparation of 205/206BiPd12AsL, 205/206BiPd12AsLN, 205/206BiPd12AsLC, and 205/206BiPd15PL, respectively. The radiometal incorporation was complete (>99% radiochemical yield) in 10 min according to radio-thin-layer chromatography. The 205/206BiPd12AsL polyanion was purified by solid-phase extraction. The incubation in rat serum showed the formation of a 205/206BiPd12AsL-protein aggregate.