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Studies of DNA binding of lanthanide platinum complexes

Scarpantonio, Luca (2011)
Ph.D. thesis, University of Birmingham.

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Abstract

Using supramolecular principles, we have been designing luminescent lanthanide complexes with a defined hairpin bis-interlacator in order to obtain luminescent probes able to recognise DNA. The complexes are comprised of Platinum(II) terpyridine, which acts as a DNA recognition site and is brought together with a "remote" luminescent lanthanide unit. All the synthetic approaches were based on the accessibility of the lanthanide-platinum complexes by the self-assembly of different components in a one pot reaction. Thus, we have been able to isolate a water soluble heterometallic complex based on thiophenal linkage named [LnPt\(_2\)]Cl\(_2\). The complex has a relatively weak lanthanide luminescence, which increases upon addition of DNA. Photophysical and DNA binding properties of the lanthanide-platinum complex were investigated by UV-vis absorption, luminescent studies and circular and linear dichroism. Oligonucleotides of twelve bases were also used to investigate the intercalation [LnPt\(_2\)]Cl\(_2\) and the mono-intercalator AATP used as control compound. Using bidimensional NMR techniques, we investigated the binding site for [LnPt\(_2\)]Cl\(_2\) and AATP upon interaction with Dickerson-Drew sequence. The sulphur lanthanide-platinum linkage in [LnPt\(_2\)]Cl\(_2\) was replaced with an acetylide one in order to introduce new photophysical features. Thus the self-assembly procedures based on DTPA-bis(amido-acetylide) and a platinum(II) terpyridine led us to isolate a new lanthanide-platinum complex named [LnC\(\equiv\)CPt\(_2\)] (CH\(_3\)SO\(_3\))\(_2\). The photophysical properties and the DNA binding properties toward interaction with CT-DNA were investigated. The complex named LnC\(\equiv\)CPt\(_2\)](CH\(_3\)S)\(_3\))\(_2\) exhibited a relatively strong lanthanide luminescence that increased upon addition of DNA. The bi-functional metal complex [EuLPt](PF\(_6\)) (where Pt=platinum-2,2':6'2"-terpyridine and L=assymmetric DTPA bisamide ligand with a thiopheno pendant arm and a quinoline moiety) was synthesised and the interaction of [EuLPt](PF\(_6\)) with CT-DNA was examined by luminescence spectroscopy, linear and circular dichroism studies and thermal denaturation studies. The [EuLPt](PF\(_6\)) retained the ability to increase its luminescence upon the addition of CT-DNA. The binding properties of the complexes were tested toward interaction with plasmid DNA by gel electrophoresis and properties such as the unwinding angle were measured. The bis-intercalators [LnPt\(_2\)]Cl\(_2\) and [LnC\(\equiv\)CPt\(_2\)](CH\(_3\)SO\(_3\))\(_2\) showed the ability to uncoil DNA almost as well as cisplatin and at low concentrations, while almost double the amount of mono-intercalators, such as [EuLPt](PF\(_6\)) is required to observe the same uncoiling effect.

Type of Work:Ph.D. thesis.
Supervisor(s):Pikramenou, Zoe
School/Faculty:Colleges (2008 onwards) > College of Engineering & Physical Sciences
Department:School of Chemistry
Subjects:QD Chemistry
RC Internal medicine
TN Mining engineering. Metallurgy
Institution:University of Birmingham
ID Code:2860
This unpublished thesis/dissertation is copyright of the author and/or third parties. The intellectual property rights of the author or third parties in respect of this work are as defined by The Copyright Designs and Patents Act 1988 or as modified by any successor legislation. Any use made of information contained in this thesis/dissertation must be in accordance with that legislation and must be properly acknowledged. Further distribution or reproduction in any format is prohibited without the permission of the copyright holder.
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