Use this URL to cite or link to this record in EThOS: https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.540997
Title: Studies of DNA binding of lanthanide platinum complexes
Author: Scarpantonio, Luca
ISNI:       0000 0004 2708 3520
Awarding Body: University of Birmingham
Current Institution: University of Birmingham
Date of Award: 2011
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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.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID: uk.bl.ethos.540997  DOI: Not available
Keywords: QD Chemistry ; RC Internal medicine ; TN Mining engineering. Metallurgy
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