Synthesis and Characterization of Neutral M^VO (M = Tc, Re) Amine-Thiol Complexes Containing a Pendant Phenylpiperidine Group

The reaction of the racemic bis(amino thio)-phenylpiperidine compound BAT-PPP with ⁹⁹TcO₄⁻ and stannous tartrate or Tc^vO(ethylene glycol)₂, resulted in two neutral isomeric complexes. In both complexes, the Tc is coordinated to an amide nitrogen atom, an amine nitrogen atom and both thiolate sulfur atoms in a square pyramidal coordination environment with oxygen in an apical position. The isomer with the pendant group syn to the Tc═O bond appears to display longer retention time in reverse phase HPLC than the anti isomer. Both isomers were characterized in the solid state and in detailed NMR studies. The TcO(BAT-PPP) syn isomer (TcOC₂₂H₃₆S₂N₃O) crystallizes in the monoclinic space group P2₁/n, with Z = 4; the cell constants are a = 12.390(2) Å,b= 11.470(2) Å,c = 18.320(3) Å, β = 103.09(1)°, and V = 2534.92(69) ų. The TcO(BAT-PPP) anti isomer (TcC₂₂H₃₆S₂N₃O) crystallizes in the orthorhombic space group Pna2₁, with Z = 8; the cell constants are a = 19.823(2) Å, b = 11.530(2) Å, c = 22.373(4) Å, and V = 5114.17(15) ų. The corresponding rhenium analogs were prepared by ligand exchange reactions. The ReO(BAT-PPP) syn isomer (ReC₂₂H₃₆S₂N₃O) crystallizes in the monoclinic space group P2₁/c with Z = 8, a = 17.681(2) Å, b = 13.425(2) Å, c = 21.301(4) Å, β = 99.81(1)°, and V = 4982.3(9) ų. The solution NMR data, taken in CDCl₃, are consistent with the structures determined by X-ray diffraction experiments. The effects of the constrained ligand system and the M═O group are clearly seen in the patterns for the syn and anti MO(BAT-PPP) (M = Tc, Re) isomers in proton and ¹³C NMR spectroscopy. The proton and ¹³C chemical shifts do not change significantly going from Tc to Re. Biodistribution differences between Tc isomers of BAT-PPP and isomers of a BAT ligand with a pendant biphenylylpiperizine (BPA) group may be rationalized in terms of the flexibility of the latter pendant group compared to the relative rigidity of the phenylpiperizine pendant group.