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

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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. et al.
In: Journal of the American Chemical Society, Vol. 145, No. 2, 18.01.2023, p. 1236-1246.

Research output: Contribution to journal › Article › peer-review

HarvardHarvard

Elgar, CE, Yusoh, NA, Tiley, PR, Kolozsvári, N, Bennett, L, Gamble, A, Péan, EV, Davies, ML, Staples, C, Ahmad, H & Gill, MR 2023, 'Ruthenium(II) Polypyridyl Complexes as FRET Donors: Structure- and Sequence-Selective DNA-Binding and Anticancer Properties', Journal of the American Chemical Society, vol. 145, no. 2, pp. 1236-1246. https://doi.org/10.1021/jacs.2c11111

APA

Elgar, C. E., Yusoh, N. A., Tiley, P. R., Kolozsvári, N., Bennett, L., Gamble, A., Péan, E. V., Davies, M. L., Staples, C., Ahmad, H., & Gill, M. 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), 1236-1246. https://doi.org/10.1021/jacs.2c11111

CBE

Elgar CE, Yusoh NA, Tiley PR, Kolozsvári N, Bennett L, Gamble A, Péan EV, Davies ML, Staples C, Ahmad H, et al. 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):1236-1246. https://doi.org/10.1021/jacs.2c11111

MLA

Elgar, Christopher E. et al. "Ruthenium(II) Polypyridyl Complexes as FRET Donors: Structure- and Sequence-Selective DNA-Binding and Anticancer Properties". Journal of the American Chemical Society. 2023, 145(2). 1236-1246. https://doi.org/10.1021/jacs.2c11111

VancouverVancouver

Elgar CE, Yusoh NA, Tiley PR, Kolozsvári N, Bennett L, Gamble A et al. Ruthenium(II) Polypyridyl Complexes as FRET Donors: Structure- and Sequence-Selective DNA-Binding and Anticancer Properties. Journal of the American Chemical Society. 2023 Jan 18;145(2):1236-1246. Epub 2023 Jan 6. doi: 10.1021/jacs.2c11111

Author

Elgar, Christopher E. ; Yusoh, Nur Aininie ; Tiley, Paul R. et al. / Ruthenium(II) Polypyridyl Complexes as FRET Donors: Structure- and Sequence-Selective DNA-Binding and Anticancer Properties. In: Journal of the American Chemical Society. 2023 ; Vol. 145, No. 2. pp. 1236-1246.

RIS

TY - JOUR

T1 - Ruthenium(II) Polypyridyl Complexes as FRET Donors: Structure- and Sequence-Selective DNA-Binding and Anticancer Properties

AU - Elgar, Christopher E.

AU - Yusoh, Nur Aininie

AU - Tiley, Paul R.

AU - Kolozsvári, Natália

AU - Bennett, Laura

AU - Gamble, Amelia

AU - Péan, Emmanuel V.

AU - Davies, Matthew L.

AU - Staples, Christopher

AU - Ahmad, Haslina

AU - Gill, Martin R.

PY - 2023/1/18

Y1 - 2023/1/18

N2 - 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) (5,5'dmb)] and [Ru(PIP) (5,5'dmb)] (dppz = dipyridophenazine, 5,5'dmb = 5,5'-dimethyl-2,2'-bipyridine, PIP = 2-phenyl-imidazo[4,5- ][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) (5,5'dmb)] acts to block DNA replication fork progression.

AB - 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) (5,5'dmb)] and [Ru(PIP) (5,5'dmb)] (dppz = dipyridophenazine, 5,5'dmb = 5,5'-dimethyl-2,2'-bipyridine, PIP = 2-phenyl-imidazo[4,5- ][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) (5,5'dmb)] acts to block DNA replication fork progression.

KW - Binding Sites

KW - Coordination Complexes - pharmacology - chemistry

KW - DNA - chemistry

KW - Fluorescence Resonance Energy Transfer

KW - Ruthenium - pharmacology - chemistry

U2 - 10.1021/jacs.2c11111

DO - 10.1021/jacs.2c11111

M3 - Article

VL - 145

SP - 1236

EP - 1246

JO - Journal of the American Chemical Society

JF - Journal of the American Chemical Society

SN - 0002-7863

IS - 2

ER -