SYNTHESIS AND CHARACTERIZATION OF NEUTRAL M(V)O (M = TC, RE) AMINE-THIOL COMPLEXES CONTAINING A PENDANT PHENYLPIPERIDINE GROUP

The reaction of the racemic bis(amino thio)-phenylpiperidine compound BAT-PPP with (TcO4-)-Tc-99 and stannous tartrate or Tc(V)O(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 P2(1)/n, with Z = 4; the cell constants are a = 12.390(2) angstrom, b = 11.470(2) angstrom, c = 18.320(3) angstrom, beta = 103.09(l)-degrees, and V = 2534.92(69) angstrom3. The TcO(BAT-PPP) anti isomer (TCC22H36S2N3O) crystallizes in the orthorhombic space group Pna2(1), with Z = 8; the cell constants are a = 19.823(2) angstrom, b = 11.530(2) angstrom, c = 22.373(4) angstrom, and V = 5114.17(15) angstrom3. The corresponding rhenium analogs were prepared by ligand exchange reactions. The ReO(BAT-PPP) syn isomer (ReC22H36S2N3O) crystallizes in the monoclinic space group P2(1)/c with Z = 8, a = 17.681(2) angstrom, b = 13.425(2) angstrom, c = 21.301(4) angstrom, beta = 99.81(1)-degrees, and V = 4982.3(9) angstrom3. 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 C-13 NMR spectroscopy. The proton and C-13 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.