Date of Award

1994

Document Type

Dissertation

Degree Name

Doctor of Philosophy (PhD)

Department

Chemistry

First Advisor

Mark L. McLaughlin

Abstract

Titanocene dichloride, a potent antitumor agent, forms a DNA-titanium adduct with Salmon Sperm DNA in 10 mM sodium perchlorate solutions ranging from pH 5 to 8.5. At physiological pH, titanocene dichloride undergoes base catalyzed hydrolysis in which the cyclopentadienyl ligands are susceptible to substitution. In chapter one of this dissertation the results of inductively coupled plasma and scintillation counting analysis of the DNA-titanium adduct formed by in vitro treatment of a DNA solution with tritiated titanocene dichloride indicate the formation of a DNA-Cp$\sb2$Ti adduct at pH 5.3 and a DNA-CpTi adduct at pH 7.0. Titanocenes prepared from bridged cyclopentadienyl ligands should exhibit greater stability towards base catalyzed hydrolysis than the cyclopentadienyl ligands of titanocene dichloride. Chapter two discusses the synthesis and characterization of bridged cyclopentadienyl ligands for this purpose. Synthesis of these novel bridged cyclopentadienyl ligands occurs by the Diels-Alder/retro-Diels-Alder reaction of the diyne, 5,6,11,12-tetradehydrodibenzo (a,e) cyclooctene, with the respective dienes: 1,3-cyclopentadiene, dimethylfulvene, and 1,2,3,4,5-pentamethylcyclopentadiene.

Pages

137

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