Graduate Program

Chemistry

Degree Name

Master of Science (MS)

Semester of Degree Completion

2005

Thesis Director

Robert Chesnut

Thesis Committee Member

Richard Keiter

Thesis Committee Member

Edward Treadwell

Thesis Committee Member

Scott Tremain

Abstract

Cisplatin, carboplatin, and oxaliplatin are used clinically for treating some cancers, but are they are not the preferred treatment for breast cancer. The usefulness of these platinum-containing drugs is limited by poor concentration of the active platinum moiety within the tumor before dose-limiting side effects are reached. One way to selectively concentrate a platinum antitumor compound in breast cancer cells is to conjugate the platinum moiety via a malonate linkage to an estrogen which selectively binds to the estrogen receptor (ER) protein. The major obstacle to linking a lipophilic estrogen to a diamino-platinum compound is the lack of solubility of estrogens in water, the typical solvent for malonate platination reactions.

The development of a nonaqueous platination method was explored with two simple malonic acid derivatives that served as models of an estrogen. model compounds were characterized by ¹H NMR, 13C NMR, IR, mass spectrometry, and elemental analysis. In DMF solution, the models were successfully coordinated to either a diaminoplatinum(II) and trans-1,2- diaminocyclohexaneplatinum(II) species. Each model complex was characterized by at least three of the following techniques: 1H NMR, 13C NMR, The 195pt NMR, mass spectrometry, and elemental analysis.

The developed nonaqueous platination method was applied to synthesis of a platinated estrogen. The DACH platinated estrogen was characterized by ¹H NMR, 195Pt NMR, mass spectrometry, and elemental analysis. The cisdimainoplatinated estrogen was characterized by mass spectrometry.

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