Ruthenium(II) Polypyridyl Complexes as FRET donors: structure- and sequence-selective DNA-binding and anticancer properties
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...
| Main Authors: | , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
American Chemical Society
2023
|
| Online Access: | http://psasir.upm.edu.my/id/eprint/103125/ http://psasir.upm.edu.my/id/eprint/103125/1/103125.pdf |
| _version_ | 1848863941697994752 |
|---|---|
| author | Elgar, Christopher E. Yusoh, Nur Aininie Tiley, Paul R. Kolozsvári, Natália Bennett, Laura G. Gamble, Amelia Péan, Emmanuel V. Davies, Matthew L. Staples, Christopher J. Ahmad, Haslina Gill, Martin R. |
| author_facet | Elgar, Christopher E. Yusoh, Nur Aininie Tiley, Paul R. Kolozsvári, Natália Bennett, Laura G. Gamble, Amelia Péan, Emmanuel V. Davies, Matthew L. Staples, Christopher J. Ahmad, Haslina Gill, Martin R. |
| author_sort | Elgar, Christopher E. |
| building | UPM Institutional Repository |
| collection | Online Access |
| 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. |
| first_indexed | 2025-11-15T13:40:55Z |
| format | Article |
| id | upm-103125 |
| institution | Universiti Putra Malaysia |
| institution_category | Local University |
| language | English |
| last_indexed | 2025-11-15T13:40:55Z |
| publishDate | 2023 |
| publisher | American Chemical Society |
| recordtype | eprints |
| repository_type | Digital Repository |
| spelling | upm-1031252025-04-21T04:27:10Z http://psasir.upm.edu.my/id/eprint/103125/ Ruthenium(II) Polypyridyl Complexes as FRET donors: structure- and sequence-selective DNA-binding and anticancer properties Elgar, Christopher E. Yusoh, Nur Aininie Tiley, Paul R. Kolozsvári, Natália Bennett, Laura G. Gamble, Amelia Péan, Emmanuel V. Davies, Matthew L. Staples, Christopher J. Ahmad, Haslina Gill, Martin R. 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. American Chemical Society 2023 Article PeerReviewed text en cc_by_4 http://psasir.upm.edu.my/id/eprint/103125/1/103125.pdf Elgar, Christopher E. and Yusoh, Nur Aininie and Tiley, Paul R. and Kolozsvári, Natália and Bennett, Laura G. and Gamble, Amelia and Péan, Emmanuel V. and Davies, Matthew L. and Staples, Christopher J. and Ahmad, Haslina and Gill, Martin R. (2023) Ruthenium(II) Polypyridyl Complexes as FRET donors: structure- and sequence-selective DNA-binding and anticancer properties. Journal of the American Chemical Society, 145 (2). pp. 1236-1246. ISSN 0002-7863; eISSN: 1520-5126 https://pubs.acs.org/doi/10.1021/jacs.2c11111 10.1021/jacs.2c11111 |
| spellingShingle | Elgar, Christopher E. Yusoh, Nur Aininie Tiley, Paul R. Kolozsvári, Natália Bennett, Laura G. Gamble, Amelia Péan, Emmanuel V. Davies, Matthew L. Staples, Christopher J. Ahmad, Haslina Gill, Martin R. Ruthenium(II) Polypyridyl Complexes as FRET donors: structure- and sequence-selective DNA-binding and anticancer properties |
| title | 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_short | 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 |
| url | http://psasir.upm.edu.my/id/eprint/103125/ http://psasir.upm.edu.my/id/eprint/103125/ http://psasir.upm.edu.my/id/eprint/103125/ http://psasir.upm.edu.my/id/eprint/103125/1/103125.pdf |