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Ruthenium(II) Polypyridyl Complexes as FRET Donors: Structure- and Sequence-Selective DNA-Binding and Anticancer Properties
,
Christopher J. Staples,
Haslina Ahmad,
Martin Gill
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 , Martin Gill
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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...
| Published in: | Journal of the American Chemical Society |
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| ISSN: | 0002-7863 1520-5126 |
| Published: |
American Chemical Society (ACS)
2023
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| Online Access: |
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| URI: | https://cronfa.swan.ac.uk/Record/cronfa62216 |
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| 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 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. |
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| College: |
Faculty of Science and Engineering |
| Funders: |
Llywodraeth Cymru - 80761-SU-242; Royal Society of Chemistry - R20-8717, E21-9540096197 |
| Issue: |
2 |
| Start Page: |
1236 |
| End Page: |
1246 |