The research is aimed at the synthesis of a fundamentally new class of chemical structures, in which a helix unites the two faces of a metallocene. The first member was recently prpared, and the proposal shows how the structure may be generalized. To construct these materials, new methods of organic synthesis would be developed, including methods reently discovered in the principal investigator's laboratory for synthesizing new ring systems and inducing specific directionality to the winding of helex molecules. A significant property anticipated for the structures to be prepared is unusual power to discriminate on the basis of stereochemistry the molecules to which a metal binds. Two experiments are proposed to test this power. One, recognizing that these structures might be the basis for yet unknown metal catalysts that are chiral directly at the metal atom, would test whether derived catalysts induce notable asymmetry in chemical reactions known to be catalized bymetallocenes and possibly in new reactions to be explored. Such studies should facilitate syntheses of chiral materials, which constitute many therapeutic agents. A second experiment relates to the recent discovery by Koepf-Maier et al. that metallocene derivatives are effective in vivo antitumor agents, and seemingly act like the useful drug cis-diammineddichloroplatinum. Because metallocenes, unline platinum compounds can be obtained helical, they could be very sensitive to the helicity of the DNA's they target. Accordingly, the plan is to see whether the ability of the enantiomers of chiral metallocenes to bind to DNA and possibly to act an antitumor agents differs significantly and to use such discrimination to probe the stereochemistry of the site in DNA at which an antitumor drug binds. To test these selectivities, structures will be prepared retaining only essential features of chirality.
The research aims at developing methods for their synthesis.
