Author Description

This dissertation, "Bismuth Based Agents and Their Interactions With the SARS Helicase and Its Metal Binding Domain" by Nan, Yang,, was obtained from The University of Hong Kong (Pokfulam, Hong Kong) and is being sold pursuant to Creative Commons: Attribution 3.0 Hong Kong License. The content of this dissertation has not been altered in any way. We have altered the formatting in order to facilitate the ease of printing and reading of the dissertation. All rights not granted by the above license are retained by the author. Abstract: Abstract of thesis entitled BISMUTH BASED AGENTS AND THEIR INTERACTIONS WITH THE SARS HELICASE AND ITS METAL BINDING DOMAIN submitted by YANG NAN for the degree of Doctor of Philosophy at The University of Hong Kong in January 2008 Bismuth, a heavy metal that exhibits high antimicrobial activities to many prokaryotes and relatively low toxicity to humans, has been used as an attractive agent in the clinic for centuries. Bismuth compounds such as bismuth tartrate, bismuth subnitrate, bismuth subsalicylate and bismuth citrate have been developed as antimicrobial medicines for the treatment of various gastrointestinal disorders and Helicobacter pylori infection. In this thesis, a series of bismuth citrate-based complexes were synthesized and characterized. All of the bismuth citrate complexes form polymeric structures with nano-sized channels. Small molecules such as water, ethylenediamine and pyridine are found inside these channels. The structure modeling of ranitidine bismuth citrate clearly shows that ranitidine can also be "stored" inside the channels of bismuth citrate polymer. Bismuth citrate-based complexes can therefore be used as a drug delivery vehicle. Furthermore, a possible degradation route of bismuth citrate-based drugs in the stomach were proposed, i.e. bismuth citrate-based drugs may at first form a three-dimensional bismuth citrate "polymeric coating" on ulcer craters to prevent the erosion by gastric aci