Effective Labeling of Amine Pharmacophores through the Employment of 2,3-Pyrazinedicarboxylic Anhydride and the Generation of fac- [M(CO) 3 (PyA)P] and cis-trans -[M(CO) 2 (PyA)P 2 ] Complexes (PyA = Pyrazine-2-carboxylate, P = Phosphine, M = Re, 99m Tc).

The fac -[M(CO) ₃ (PyA)(P)] and cis-trans -[M(CO) ₂ (PyA)(P) ₂ ] neutral complexes (M is Re or ^99m Tc), based on the mixed ligand strategy with pyrazine-2-carboxylic acid (PyAH) as the bidentate N,O and triphenylphosphine as the monodentate P ligand, are presented. Through the employment of the anhydride of pyrazine-2,3-dicarboxylic acid (PyDA), the PyAH scaffold was conveniently derivatized with the model bioactive amine 1-(2-methoxyphenyl)piperazine, the active part of the 5-HT _1A antagonist WAY100635. Reaction of either PyAH or the pharmacophore-bearing PyAH ligand (L ¹ H) with fac- [M(CO) ₃ ] ⁺ core in water yielded the intermediate fac -[M(CO) ₃ (PyA)(H ₂ O)] complexes. The labile aqua ligand was easily replaced by PPh ₃ to yield the fac -[Re(CO) ₃ (PyA)(PPh ₃ )] complexes, while in toluene under reflux, the cis-trans -[Re(CO) ₂ (PyA)(PPh ₃ ) ₂ ] complexes were obtained. The latter complexes were alternatively obtained from mer -[Re(CO) ₃ (PPh ₃ ) ₂ Cl] by refluxing with the PyA ligand in toluene. The analogous ^99m Tc complexes were synthesized quantitatively, showing excellent stability in competition studies. The methodology described herein represents a practical procedure for the effective integration of the fac -[M(CO) ₃ ] ⁺ core with amine-bearing biologically active compounds for diagnosis/therapy.