Title

Transition metal complexes of nucleosides for cancer chemotherapy

Author

Jun Chen

Date of Award

2016

Degree Name

M.S. in Chemistry

Department

Department of Chemistry

Advisor/Chair

Advisor: Kevin M. Church

Abstract

Platinum(II) complexes of the type PtCl₂L₂, such as cisplatin---PtCl₂ (NH₃)₂, have been widely studied and shown to have anti-tumor activity. On the other hand, ruthenium(II) complexes are known for their intense photophysical properties, biodiversity, and tumor targeting capabilities, which make them suitable as photosensitizers in photodynamic therapy. The efficacy of these complexes as anti-tumor agents is controlled by many variables such as cell permeability, availability of DNA repair processes, etc. A platinum(II)-DMSO complex and a ruthenium(II)-bypyridine complex have been incorporated into a thymidine based nucleoside through an N-3 pendant pyridyl nitrogen. Nucleosides are transported into the cell by particular trans-membrane proteins. This could increase the cellular uptake and reduce toxic side effects. Incubation of these two complexes with pUC18 circular plasmid DNA has been performed and followed by gel electrophoresis. The results show the formation of linearized forms of DNA. The structures of all intermediates and final compounds were confirmed by 1D-NMR (¹H-NMR and ¹³C-NMR), 2D-NMR (H-C correlation, HMQC and HMBC), TOF-MS and ¹⁹⁵Pt-NMR methodologies.

Keywords

Nucleosides, Platinum compounds, Ruthenium compounds, Chemotherapy, Chemistry, Nucleoside complex, DNA crosslinking activity, photodynamic therapy, ruthenium, transition metals

Rights Statement

Copyright 2016, author

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