Novel lipophilic amidate oxorhenium and oxotechnetium complexes as potential brain agents: Synthesis, characterization and biological evaluation

Novel oxorhenium and oxotechnetium complexes based on the tetradentate 1-(2 -hydroxybenzamido)-2-(pyridinecarboxamido)benzene, H3L, ligand have been sy nthesized and characterized herein. Thus, by reacting equimolar quantities of the triply deprotonated ligand L3- With the suitable MO3+ precursor, the following neutral MOL complexes could be easily produced following similar synthetic routes: M=Re (1), M=(TC)-T-99g (2) and M=Tc-99m (3). Complexes 1 and 2, prepared in macroscopic amounts, were chemically characterized and their structure determined by single-crystal X-ray analysis. They are isost ructural metal chelates, adopting a distorted square pyramidal geometry aro und the metal. The N3O donor atom set of the tetradentate ligand defines th e basal plane and the oxygen atom of the M=O core occupies the apex of the pyramid. Complex 3 forms quantitatively at tracer level by mixing the H3L l igand with (NaTcO4)-Tc-99m generator eluate in aqueous alkaline media and u sing tin chloride as reductant in the presence of citrate. Its structure wa s established by chromatographic comparison with prototypic complexes 1 and 2 using high-performance liquid chromatographic techniques. When challenge d with excess glutathione in vitro, complex 3 is rapidly converted to hydro philic unidentified metal species. Tissue distribution data after administr ation of complex 3 in vivo revealed a significant uptake and retention of t his compound in brain tissue.