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Ruthenium(II) Polypyridyl Complexes as FRET Donors: Structure- and Sequence-Selective DNA-Binding and Anticancer Properties

Chris Elgar, Nur Aininie Yusoh, Paul Tiley, Natalia Kolozsvari, Laura G. Bennett, Amelia Gamble, Emmanuel Pean, Matthew Davies Orcid Logo, Christopher J. Staples, Haslina Ahmad, Martin Gill Orcid Logo

Journal of the American Chemical Society, Volume: 145, Issue: 2, Pages: 1236 - 1246

Swansea University Authors: Chris Elgar, Paul Tiley, Natalia Kolozsvari, Emmanuel Pean, Matthew Davies Orcid Logo, Martin Gill Orcid Logo

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DOI (Published version): 10.1021/jacs.2c11111

Abstract

Ruthenium(II) polypyridyl complexes (RPCs) that emit from metal-to-ligand charge transfer (MLCT) states have been developed as DNA probes and are being examined as potential anticancer agents. Here, we report that MLCT-emissive RPCs that bind DNA undergo Förster resonance energy transfer (FRET) with...

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Published in: Journal of the American Chemical Society
ISSN: 0002-7863 1520-5126
Published: American Chemical Society (ACS) 2023
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URI: https://cronfa.swan.ac.uk/Record/cronfa62216
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Here, we report that MLCT-emissive RPCs that bind DNA undergo Förster resonance energy transfer (FRET) with Cy5.5-labeled DNA, forming mega-Stokes shift FRET pairs. Based on this discovery, we developed a simple and rapid FRET binding assay to examine DNA-binding interactions of RPCs with diverse photophysical properties, including non-“light switch” complexes [Ru(dppz)2(5,5′dmb)]2+ and [Ru(PIP)2(5,5′dmb)]2+ (dppz = dipyridophenazine, 5,5′dmb = 5,5′-dimethyl-2,2′-bipyridine, PIP = 2-phenyl-imidazo[4,5-f][1,10]phenanthroline). Binding affinities toward duplex, G-quadruplex, three-way junction, and mismatch DNA were determined, and derived FRET donor–acceptor proximities provide information on potential binding sites. 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spelling v2 62216 2022-12-28 Ruthenium(II) Polypyridyl Complexes as FRET Donors: Structure- and Sequence-Selective DNA-Binding and Anticancer Properties 0b1472bd724711f7a76cdfacf492a877 Chris Elgar Chris Elgar true false 36246328a726c8861982cd62dee7327b Paul Tiley Paul Tiley true false 8e420c0021b2ede0cfa9cc8bda049ed3 Natalia Kolozsvari Natalia Kolozsvari true false fe9108445b985e2687ca3ccfc5c73812 Emmanuel Pean Emmanuel Pean true false 4ad478e342120ca3434657eb13527636 0000-0003-2595-5121 Matthew Davies Matthew Davies true false 485d85b532851e8863cd19c6af7e00f7 0000-0002-1371-5676 Martin Gill Martin Gill true false 2022-12-28 CHEM Ruthenium(II) polypyridyl complexes (RPCs) that emit from metal-to-ligand charge transfer (MLCT) states have been developed as DNA probes and are being examined as potential anticancer agents. Here, we report that MLCT-emissive RPCs that bind DNA undergo Förster resonance energy transfer (FRET) with Cy5.5-labeled DNA, forming mega-Stokes shift FRET pairs. Based on this discovery, we developed a simple and rapid FRET binding assay to examine DNA-binding interactions of RPCs with diverse photophysical properties, including non-“light switch” complexes [Ru(dppz)2(5,5′dmb)]2+ and [Ru(PIP)2(5,5′dmb)]2+ (dppz = dipyridophenazine, 5,5′dmb = 5,5′-dimethyl-2,2′-bipyridine, PIP = 2-phenyl-imidazo[4,5-f][1,10]phenanthroline). Binding affinities toward duplex, G-quadruplex, three-way junction, and mismatch DNA were determined, and derived FRET donor–acceptor proximities provide information on potential binding sites. Molecules characterized by this method demonstrate encouraging anticancer properties, including synergy with the PARP inhibitor Olaparib, and mechanistic studies indicate that [Ru(PIP)2(5,5′dmb)]2+ acts to block DNA replication fork progression. Journal Article Journal of the American Chemical Society 145 2 1236 1246 American Chemical Society (ACS) 0002-7863 1520-5126 19 1 2023 2023-01-19 10.1021/jacs.2c11111 COLLEGE NANME Chemistry COLLEGE CODE CHEM Swansea University SU Library paid the OA fee (TA Institutional Deal) Llywodraeth Cymru - 80761-SU-242; Royal Society of Chemistry - R20-8717, E21-9540096197 2023-06-12T16:25:35.3020677 2022-12-28T11:33:01.3018337 Faculty of Science and Engineering School of Engineering and Applied Sciences - Chemistry Chris Elgar 1 Nur Aininie Yusoh 2 Paul Tiley 3 Natalia Kolozsvari 4 Laura G. Bennett 5 Amelia Gamble 6 Emmanuel Pean 7 Matthew Davies 0000-0003-2595-5121 8 Christopher J. Staples 9 Haslina Ahmad 10 Martin Gill 0000-0002-1371-5676 11 62216__26251__fa8eac440af743b58aa3a09d0b321af6.pdf 62216.pdf 2023-01-11T13:25:28.0912264 Output 4490560 application/pdf Version of Record true Released under the terms of a Creative Commons Attribution 4.0 International (CC BY 4.0) License. true eng https://creativecommons.org/licenses/by/4.0/
title Ruthenium(II) Polypyridyl Complexes as FRET Donors: Structure- and Sequence-Selective DNA-Binding and Anticancer Properties
spellingShingle Ruthenium(II) Polypyridyl Complexes as FRET Donors: Structure- and Sequence-Selective DNA-Binding and Anticancer Properties
Chris Elgar
Paul Tiley
Natalia Kolozsvari
Emmanuel Pean
Matthew Davies
Martin Gill
title_short Ruthenium(II) Polypyridyl Complexes as FRET Donors: Structure- and Sequence-Selective DNA-Binding and Anticancer Properties
title_full Ruthenium(II) Polypyridyl Complexes as FRET Donors: Structure- and Sequence-Selective DNA-Binding and Anticancer Properties
title_fullStr Ruthenium(II) Polypyridyl Complexes as FRET Donors: Structure- and Sequence-Selective DNA-Binding and Anticancer Properties
title_full_unstemmed Ruthenium(II) Polypyridyl Complexes as FRET Donors: Structure- and Sequence-Selective DNA-Binding and Anticancer Properties
title_sort Ruthenium(II) Polypyridyl Complexes as FRET Donors: Structure- and Sequence-Selective DNA-Binding and Anticancer Properties
author_id_str_mv 0b1472bd724711f7a76cdfacf492a877
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author_id_fullname_str_mv 0b1472bd724711f7a76cdfacf492a877_***_Chris Elgar
36246328a726c8861982cd62dee7327b_***_Paul Tiley
8e420c0021b2ede0cfa9cc8bda049ed3_***_Natalia Kolozsvari
fe9108445b985e2687ca3ccfc5c73812_***_Emmanuel Pean
4ad478e342120ca3434657eb13527636_***_Matthew Davies
485d85b532851e8863cd19c6af7e00f7_***_Martin Gill
author Chris Elgar
Paul Tiley
Natalia Kolozsvari
Emmanuel Pean
Matthew Davies
Martin Gill
author2 Chris Elgar
Nur Aininie Yusoh
Paul Tiley
Natalia Kolozsvari
Laura G. Bennett
Amelia Gamble
Emmanuel Pean
Matthew Davies
Christopher J. Staples
Haslina Ahmad
Martin Gill
format Journal article
container_title Journal of the American Chemical Society
container_volume 145
container_issue 2
container_start_page 1236
publishDate 2023
institution Swansea University
issn 0002-7863
1520-5126
doi_str_mv 10.1021/jacs.2c11111
publisher American Chemical Society (ACS)
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 Ruthenium(II) polypyridyl complexes (RPCs) that emit from metal-to-ligand charge transfer (MLCT) states have been developed as DNA probes and are being examined as potential anticancer agents. Here, we report that MLCT-emissive RPCs that bind DNA undergo Förster resonance energy transfer (FRET) with Cy5.5-labeled DNA, forming mega-Stokes shift FRET pairs. Based on this discovery, we developed a simple and rapid FRET binding assay to examine DNA-binding interactions of RPCs with diverse photophysical properties, including non-“light switch” complexes [Ru(dppz)2(5,5′dmb)]2+ and [Ru(PIP)2(5,5′dmb)]2+ (dppz = dipyridophenazine, 5,5′dmb = 5,5′-dimethyl-2,2′-bipyridine, PIP = 2-phenyl-imidazo[4,5-f][1,10]phenanthroline). Binding affinities toward duplex, G-quadruplex, three-way junction, and mismatch DNA were determined, and derived FRET donor–acceptor proximities provide information on potential binding sites. Molecules characterized by this method demonstrate encouraging anticancer properties, including synergy with the PARP inhibitor Olaparib, and mechanistic studies indicate that [Ru(PIP)2(5,5′dmb)]2+ acts to block DNA replication fork progression.
published_date 2023-01-19T16:25:33Z
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