The principal problem which this research proposal addresses is that of the development of NOVEL PHARMACOLOGIC AGENTS FOR THE REMOVAL OF EXCESSIVE ACCUMULATIONS OF METAL IONS FROM THE BODY. The goal of this research will be to ultimately develop a medium-sized ring polythioether chelate which will selectively complex specific toxic metal ions. Each of the medium-sized ring polythioethers that will be synthesized has some unique structural aspect that might influence its complexation characteristics. By examining how these structural alterations on the thioethers change their complexation behavior, it may be possible to design a specific medium-sized ring polythioether that will complex one particular transition metal ion, creating a highly selective metal binding system. These ligands would be able to selectively chelate and remove highly toxic metal ions such as lead, mercury, and cadmium. Research is needed in order to determine: (a) the optimum synthetic techniques for the preparation of these medium-sized ligands (b) the effect that structural alterations on the ligands have on the ease of complex formation, complex stability, and complex structure (c) the complexation behavior of a wide range of transition metal ions, especially toxic metal ions, towards these ligands. Ring size effects, chelate ring size changes, and changes in steric rigidity will be studied to see how these changes influence the thioether-transition metal ion interaction. The syntheses of several novel medium-sized ring tridentate thioether ligands which incorporate these structural features will be undertaken. The information gained from this research will be useful in developing novel selective chelate systems designed for the removal of trace toxic metals from the body.
