الفهرس 
General IntroductionOnly 14 pages are availabe for public view
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Abstract
The work described herein concentrates on the use of various analytical techniques to study the interaction of novel metallo anticancer compounds with their possible biological targets and factors affecting such interactions.
Chapter one, ”General Introduction”~ provides a quick view covering the malO concepts and techniques utilized throughout this work. This was followed by the ”Experimental” in chapter two, describing in details materials, apparatus and methods used in this thesis.
The results and discussion ”Chapter Four” was divided into three parts; part one studies DNA binding of metallosupramolecular iron cylinders while parts two and three investigates novel metallo steroidal anticancer compounds, where part two investigates DNA and protein binding studies of a steroidal platinum complex, while part three reports the results of studying DNA binding of a steroidal RJ1enium complex.
Part one (section 4.1) entitled ”DNA binding studies of Iron cylinders” compares three different Iron cylinder derivatives to the parent one using linear and circular dichroism, ethidium bromide displacement and gel electrophoresis. A new non radioactive method was developed and optimized to investigate 3WJ binding of Iron cylinders. Surface Plasmon resonance was also used to determine the equilibrium binding constant of the parent cylinder and ethidium bromide to DNA.
In part two (section 4.2), ”DNA and protein binding studies of a steroidal platinum complex”, the binding of a synthetic steroid triammine cis cationic platinum(II) complex to important biological targets was studied using ethidium bromide displacement and electrophoretic mobility shift assay. This complex has molecular design concept of using the steroid moiety as a transport and localisation motif to deliver a DNA-binding platinum unit into the nucleus.
Part three (section 4.3), ”DNA binding study of a steroidal Rhenium complex”, explored the interaction of a novel steroid rhenium complex and its cytotoxicity mechanism. This complex was developed to target and image androgen receptors, later it was surprisingly found to be cytotoxic. The first biological target interaction to be explored was DNA, through ESI-MS nucleobase binding, gel electrophoresis of its interaction with plasmid DNA, UV -Vis, fluorescence, circular and linear dichroism titrations.
5.2.1 For Iron Cylinders
The introduction of different groups (phenyl, 2- and 4-yridine) resulted in decreasing the interaction of the cylinders with DNA which reinforces the conclusion that their shape was the key and is in accordance with previous studies. Since those derivatives were of lower binding ability, they were abandoned and research will now focus on exploring cylinder conjugates.
The results of SPR experiment showed ethidium bromide to have a stronger binding affinity to DNA compared to Pc. This may seem contradictory to the results of etidium bromide displacement assay showing PC and its derivatives 10 be able to displace EB from its DNA biding sites. However, this is not the case; determining the equilibrium dissociation constant is not sufficient on its own to predict the outcome in a competition, a more detailed kinetic study using a different model not assuming the obedience of law of mass action clearly showed EB to have faster dissociation from DNA. DNA binding constant determination is usually very challenging because of the heterogeneity of affinity of its different binding sites and modes.
A new method was explored and optimized to visualize gels using a fluorescent labelled oligonucleotide and Odyssey infra red irpaging system. This method was used to further investigate 3WJ binding and results showed that PC recognises three-way junction and binds to it which is a real and potentially very powerful new mode of DNA recognition.
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The results confirm that both M and P enantiomers can stabilise the three-way junction
structure, but that M is more effective than P as evidenced by calculated constants.