Ruthenium (II) polypyridyl complexes as photoprobes for DNA mismatches

TILEY, PAUL

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Ruthenium (II) polypyridyl complexes as photoprobes for DNA mismatches / PAUL TILEY

Swansea University Author: PAUL TILEY

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Abstract

[Ru(bpy)2dppz]2+ is a classic “light switch” effect complex with a brighter emission for mismatched DNA than well-matched DNA. It is, therefore, a photoprobe for DNA. To enhance its selectivity for mismatched base pairs which can lead to DNA mutations, a range of related complexes were synthesized a...

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Published:	Swansea 2022
Institution:	Swansea University
Degree level:	Master of Research
Degree name:	MSc by Research
Supervisor:	Gill, Martin
URI:	https://cronfa.swan.ac.uk/Record/cronfa59830
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first_indexed	2022-04-14T13:25:05Z
last_indexed	2022-04-15T03:31:24Z
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fullrecord	<?xml version="1.0"?><rfc1807><datestamp>2022-04-14T14:32:08.1458918</datestamp><bib-version>v2</bib-version><id>59830</id><entry>2022-04-14</entry><title>Ruthenium (II) polypyridyl complexes as photoprobes for DNA mismatches</title><swanseaauthors><author><sid>b841a4b398befea45ae5897076318053</sid><firstname>PAUL</firstname><surname>TILEY</surname><name>PAUL TILEY</name><active>true</active><ethesisStudent>false</ethesisStudent></author></swanseaauthors><date>2022-04-14</date><abstract>[Ru(bpy)2dppz]2+ is a classic “light switch” effect complex with a brighter emission for mismatched DNA than well-matched DNA. It is, therefore, a photoprobe for DNA. To enhance its selectivity for mismatched base pairs which can lead to DNA mutations, a range of related complexes were synthesized and investigated. The approach involved increasing the steric bulk of the ancillary 2,2’-bipyridine (bpy) ligands and/or the dipyridophenazine (dppz) functional group ligand. This functional group ligand is known to insert or intercalate between adjacent base pairs in the base stack of DNA and an alternative functional group ligand was also explored: 12,17-dihydronaphthodipyridophenazine-12,17-dione (aqphen). Hairpin and 12 base oligonucleotide duplex DNA containing mismatched base pairs were tested and compared to the same sequences containing well-matched base pairs. Methylation of the ancillary bpy ligands only at positions 5,5’ with dppz as the functional group ligand is highly selective for both the CC and the TT mismatches. For the former the signal is between 4 and 6.3x higher than it is for well-matched DNA and for the latter a 6x increase was recorded. It almost certainly binds to the DNA via intercalation and its performance in these experiments have identified a useful photoprobe for the identification of these mismatched base pairings. Methylation of the dppz functional group ligand at positions 10 and 12 produced large increases in emission intensity compared to the parent compound [Ru(bpy)2dppz]2+ but did not substantially increase the mismatch base pair selectivity. The use of aqphen instead of dppz as the functional group ligand increased the binding strength with DNA and, notably, it showed a higher binding affinity for a 12mer duplex containing a CC mismatched base pair versus the well-matched sequence; its mode of binding is likely to be intercalation. In summary, enhancing steric bulk through methylation of the ancillary bpy ligands has achieved the desired selectivity whilst the same modification to the inserting dppz functional group ligand has led to large increases in signal intensity without an improvement in selectivity. The use of aqphen as the functional group ligand, which also has a greater steric bulk compared to dppz, increased binding affinity as well as selectivity.</abstract><type>E-Thesis</type><journal/><volume/><journalNumber/><paginationStart/><paginationEnd/><publisher/><placeOfPublication>Swansea</placeOfPublication><isbnPrint/><isbnElectronic/><issnPrint/><issnElectronic/><keywords>Ruthenium (II) polypyridyl complexes, photoprobes, well-matched and mismatched DNA base pairs</keywords><publishedDay>4</publishedDay><publishedMonth>4</publishedMonth><publishedYear>2022</publishedYear><publishedDate>2022-04-04</publishedDate><doi/><url/><notes/><college>COLLEGE NANME</college><CollegeCode>COLLEGE CODE</CollegeCode><institution>Swansea University</institution><supervisor>Gill, Martin</supervisor><degreelevel>Master of Research</degreelevel><degreename>MSc by Research</degreename><apcterm/><lastEdited>2022-04-14T14:32:08.1458918</lastEdited><Created>2022-04-14T14:22:44.1693823</Created><path><level id="1">Faculty of Science and Engineering</level><level id="2">School of Engineering and Applied Sciences - Chemistry</level></path><authors><author><firstname>PAUL</firstname><surname>TILEY</surname><order>1</order></author></authors><documents><document><filename>59830__23866__26bc7bca0135446b9c5535d4691d671f.pdf</filename><originalFilename>Tiley_Paul_MRes_Thesis_Final_Redacted_Signature.pdf</originalFilename><uploaded>2022-04-14T14:28:22.7642250</uploaded><type>Output</type><contentLength>4419810</contentLength><contentType>application/pdf</contentType><version>E-Thesis – open access</version><cronfaStatus>true</cronfaStatus><documentNotes>Copyright: The author, Paul Tiley, 2022.</documentNotes><copyrightCorrect>true</copyrightCorrect><language>eng</language></document></documents><OutputDurs/></rfc1807>
spelling	2022-04-14T14:32:08.1458918 v2 59830 2022-04-14 Ruthenium (II) polypyridyl complexes as photoprobes for DNA mismatches b841a4b398befea45ae5897076318053 PAUL TILEY PAUL TILEY true false 2022-04-14 [Ru(bpy)2dppz]2+ is a classic “light switch” effect complex with a brighter emission for mismatched DNA than well-matched DNA. It is, therefore, a photoprobe for DNA. To enhance its selectivity for mismatched base pairs which can lead to DNA mutations, a range of related complexes were synthesized and investigated. The approach involved increasing the steric bulk of the ancillary 2,2’-bipyridine (bpy) ligands and/or the dipyridophenazine (dppz) functional group ligand. This functional group ligand is known to insert or intercalate between adjacent base pairs in the base stack of DNA and an alternative functional group ligand was also explored: 12,17-dihydronaphthodipyridophenazine-12,17-dione (aqphen). Hairpin and 12 base oligonucleotide duplex DNA containing mismatched base pairs were tested and compared to the same sequences containing well-matched base pairs. Methylation of the ancillary bpy ligands only at positions 5,5’ with dppz as the functional group ligand is highly selective for both the CC and the TT mismatches. For the former the signal is between 4 and 6.3x higher than it is for well-matched DNA and for the latter a 6x increase was recorded. It almost certainly binds to the DNA via intercalation and its performance in these experiments have identified a useful photoprobe for the identification of these mismatched base pairings. Methylation of the dppz functional group ligand at positions 10 and 12 produced large increases in emission intensity compared to the parent compound [Ru(bpy)2dppz]2+ but did not substantially increase the mismatch base pair selectivity. The use of aqphen instead of dppz as the functional group ligand increased the binding strength with DNA and, notably, it showed a higher binding affinity for a 12mer duplex containing a CC mismatched base pair versus the well-matched sequence; its mode of binding is likely to be intercalation. In summary, enhancing steric bulk through methylation of the ancillary bpy ligands has achieved the desired selectivity whilst the same modification to the inserting dppz functional group ligand has led to large increases in signal intensity without an improvement in selectivity. The use of aqphen as the functional group ligand, which also has a greater steric bulk compared to dppz, increased binding affinity as well as selectivity. E-Thesis Swansea Ruthenium (II) polypyridyl complexes, photoprobes, well-matched and mismatched DNA base pairs 4 4 2022 2022-04-04 COLLEGE NANME COLLEGE CODE Swansea University Gill, Martin Master of Research MSc by Research 2022-04-14T14:32:08.1458918 2022-04-14T14:22:44.1693823 Faculty of Science and Engineering School of Engineering and Applied Sciences - Chemistry PAUL TILEY 1 59830__23866__26bc7bca0135446b9c5535d4691d671f.pdf Tiley_Paul_MRes_Thesis_Final_Redacted_Signature.pdf 2022-04-14T14:28:22.7642250 Output 4419810 application/pdf E-Thesis – open access true Copyright: The author, Paul Tiley, 2022. true eng
title	Ruthenium (II) polypyridyl complexes as photoprobes for DNA mismatches
spellingShingle	Ruthenium (II) polypyridyl complexes as photoprobes for DNA mismatches PAUL TILEY
title_short	Ruthenium (II) polypyridyl complexes as photoprobes for DNA mismatches
title_full	Ruthenium (II) polypyridyl complexes as photoprobes for DNA mismatches
title_fullStr	Ruthenium (II) polypyridyl complexes as photoprobes for DNA mismatches
title_full_unstemmed	Ruthenium (II) polypyridyl complexes as photoprobes for DNA mismatches
title_sort	Ruthenium (II) polypyridyl complexes as photoprobes for DNA mismatches
author_id_str_mv	b841a4b398befea45ae5897076318053
author_id_fullname_str_mv	b841a4b398befea45ae5897076318053_***_PAUL TILEY
author	PAUL TILEY
author2	PAUL TILEY
format	E-Thesis
publishDate	2022
institution	Swansea University
college_str	Faculty of Science and Engineering
hierarchytype
hierarchy_top_id	facultyofscienceandengineering
hierarchy_top_title	Faculty of Science and Engineering
hierarchy_parent_id	facultyofscienceandengineering
hierarchy_parent_title	Faculty of Science and Engineering
department_str	School of Engineering and Applied Sciences - Chemistry{{{_:::_}}}Faculty of Science and Engineering{{{_:::_}}}School of Engineering and Applied Sciences - Chemistry
document_store_str	1
active_str	0
description	[Ru(bpy)2dppz]2+ is a classic “light switch” effect complex with a brighter emission for mismatched DNA than well-matched DNA. It is, therefore, a photoprobe for DNA. To enhance its selectivity for mismatched base pairs which can lead to DNA mutations, a range of related complexes were synthesized and investigated. The approach involved increasing the steric bulk of the ancillary 2,2’-bipyridine (bpy) ligands and/or the dipyridophenazine (dppz) functional group ligand. This functional group ligand is known to insert or intercalate between adjacent base pairs in the base stack of DNA and an alternative functional group ligand was also explored: 12,17-dihydronaphthodipyridophenazine-12,17-dione (aqphen). Hairpin and 12 base oligonucleotide duplex DNA containing mismatched base pairs were tested and compared to the same sequences containing well-matched base pairs. Methylation of the ancillary bpy ligands only at positions 5,5’ with dppz as the functional group ligand is highly selective for both the CC and the TT mismatches. For the former the signal is between 4 and 6.3x higher than it is for well-matched DNA and for the latter a 6x increase was recorded. It almost certainly binds to the DNA via intercalation and its performance in these experiments have identified a useful photoprobe for the identification of these mismatched base pairings. Methylation of the dppz functional group ligand at positions 10 and 12 produced large increases in emission intensity compared to the parent compound [Ru(bpy)2dppz]2+ but did not substantially increase the mismatch base pair selectivity. The use of aqphen instead of dppz as the functional group ligand increased the binding strength with DNA and, notably, it showed a higher binding affinity for a 12mer duplex containing a CC mismatched base pair versus the well-matched sequence; its mode of binding is likely to be intercalation. In summary, enhancing steric bulk through methylation of the ancillary bpy ligands has achieved the desired selectivity whilst the same modification to the inserting dppz functional group ligand has led to large increases in signal intensity without an improvement in selectivity. The use of aqphen as the functional group ligand, which also has a greater steric bulk compared to dppz, increased binding affinity as well as selectivity.
published_date	2022-04-04T04:17:26Z
_version_	1763754163373604864
score	11.014224

Ruthenium (II) polypyridyl complexes as photoprobes for DNA mismatches / PAUL TILEY

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