Yanling Chen

Graduation Semester and Year

2013

Language

English

Document Type

Thesis

Degree Name

Master of Science in Chemistry

Department

Chemistry and Biochemistry

First Advisor

Frederick M MacDonnell

Abstract

Research on biological activities of ruthenium polypyridyl complexes (RPCs) continues to attract interest as these complexes have shown promising anticancer activity both in vitro and in vivo.¹⁻³ The mononuclear RPC, [(phen)₂Ru(tatpp)]²⁺ (MP) and related dinuclear complex [(phen)₂Ru(tatpp)Ru(phen)₂]⁴⁺ (P) have been shown to both intercalate with DNA and shown potentiated DNA cleavage under anaerobic and reducing conditions⁴⁻⁵, as well as shown good selectivity and cytotoxicity towards malignant cell lines in vitro and tumors in vivo.⁵ Both complexes contain the redox-active tatpp ligand which is thought to be an essential component for the observed biological activities. This thesis is focused on developing improvements to the stereoselective syntheses of the chiral complexes, ΔΔ-P and Δ-MP. It is also investigated the synthesis of a new analogue [(phen)₂Ru(tadbp)]²⁺ (B) and its chiral form Δ-B which contains a modified tatpp ligand that is only capable of binding one Ru ion. Moreover this thesis explores the ability of these large complexes to traverse the cell membranes and get into cells and cell nuclei by isolating treated cells and nuclei and determining their ruthenium content by graphite furnace atomic absorption method (GFAAS). The GFAAS data show that the two examined complexes ΔΔ-P and Δ-MP are able to quickly penetrate into cancer cells (H-358) and concentrate in nuclei, which is postulated due to their high binding affinity to DNA.

Disciplines

Chemistry | Physical Sciences and Mathematics

Comments

Degree granted by The University of Texas at Arlington

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