Synthesis and characterization of neutral oxotechnetium(V) bisaminoethanethiol complexes: potential brain imaging agents

Abstract

Neutral and lipophilic technetium complexes, 99TcO(BAT-TE), 99TcO(BP-BAT- TM) and 99TcO(BP-BAT-TE), where the ligands are ethane -1,2-bis(N-1-amino-3-ethyl- butyl-3-thiol), biphenyl-2,2′-bis(N-1-amino-2-methylpropane-2-thiol) and biphenyl-2,2′- bis(bis(N-1-amino-3- ethylbutyl-3-thiol)), respectively, have been prepared by direct reduction of TcO 4 − with stannous tartrate in the presence of the ligand. The first complex, TcO(BAT-TE), crystallizes from ether in the monoclinic space group P2 1/ c with a = 12.453(2), b = 11.747(1), c = 12.645(2) Å, β = 99.66(0)°, Z = 4, R = 0.030 and R w = 0.039. The second complex, TcO(BP-BAT-TE), crystallizes from hexane/ether (70/30) in the monoclinic space group P2 1/ c with a = 10.397(1), b = 17.039(2), c = 14.446(1) Å, β = 110.09(1)°, Z = 4, R = 0.030 and R w = 0.042. X-ray crystallography data show that the metal ions in TcO(BAT-TE) and TcO(BP-BAT-TE) are in a distorted square pyramidal coordination environment with the oxygen at an apical position. The biphenyl diamine backbone of TcO(BP-BAT-TE) forms a seven-membered chelate ring with the proton of the amine nitrogen anti relative to the -yl oxygen; on the contrary, the amine proton in the TcO(BAT-TE) complex is syn relative to the oxygen. These structures appear to be maintained in solution as observed from proton NMR studies. The effect of lipophilicity on brain uptake is illustrated in the context of these molecules.