The clinical utility of technetium-based radiopharmaceuticals for imaging makes designing appropriate therapeutic agents complementing the 99mTc-imaging pharmaceuticals advantageous. Rhenium, the third-row congener of technetium, has two radioisotopes useful for developing therapeutic radiopharmaceuticals, 186Re and 188Re. Rhenium(V) is the most accessible oxidation state from perrhenate, the chemical form available at the radiotracer level. Forming kinetically stable Re(V) complexes under in vivo conditions is much more challenging than for Tc(V) because of the susceptibility for re-oxidation to perrhenate. The successful development of therapeutic 186/188Re agents hinges on the design of chelators that form kinetically inert complexes with the Re(V) metal center. To better understand which ligands most likely form thermodynamically stable complexes with monooxorhenium(V), a computational search of a series of monoamine-monoamide dithiol (MAMA) and bisaminothiol (BAT) ligands was performed. These studies also compare analogous ligands that replace the N2S2 systems of the MAMA and BAT ligands with N2O2, N2Se2 and P2S2 coordinating atoms to determine if changing the heteroatom will improve complex stability. Additionally, NO3, NS3, NSe3, and PS3 ligands were investigated. Preliminary in silico results showed that P2S2 complexes are more thermodynamically stable than the other ligands. P2S2 ligands, previously prepared for rhodium(III) complexation, have been modified for use with monooxorhenium(V). The computational findings for all of the ligands, experimental preparation of the P2S2 ligand and the preliminary complexation of monooxorhenium(V) will be discussed.

Hunt for the most thermodynamically stable ligand for <sup>186/188</sup>Re(V): A computational and experimental approach

248th National Meeting (2014)

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Hunt for the most thermodynamically stable ligand for 186/188Re(V): A computational and experimental approach

Hunt for the most thermodynamically stable ligand for ^186/188Re(V): A computational and experimental approach