Tuning the reactivity of osmium(II) and ruthenium(II) arene complexes under physiological conditions

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Tuning the reactivity of osmium(II) and ruthenium(II) arene complexes under physiological conditions. / Peacock, Anna; Habtemariam, A; Fernandez, R; Walland, V; Fabbiani, FPA; Parsons, S; Aird, RE; Jodrell, DI; Sadler, PJ.

In: Journal of the American Chemical Society, Vol. 128, No. 5, 08.02.2006, p. 1739-1748.

Research output: Contribution to journalReview article

Harvard

Peacock, A, Habtemariam, A, Fernandez, R, Walland, V, Fabbiani, FPA, Parsons, S, Aird, RE, Jodrell, DI & Sadler, PJ 2006, 'Tuning the reactivity of osmium(II) and ruthenium(II) arene complexes under physiological conditions', Journal of the American Chemical Society, vol. 128, no. 5, pp. 1739-1748. https://doi.org/10.1021/ja055886r

APA

Peacock, A., Habtemariam, A., Fernandez, R., Walland, V., Fabbiani, FPA., Parsons, S., Aird, RE., Jodrell, DI., & Sadler, PJ. (2006). Tuning the reactivity of osmium(II) and ruthenium(II) arene complexes under physiological conditions. Journal of the American Chemical Society, 128(5), 1739-1748. https://doi.org/10.1021/ja055886r

Vancouver

Author

Peacock, Anna ; Habtemariam, A ; Fernandez, R ; Walland, V ; Fabbiani, FPA ; Parsons, S ; Aird, RE ; Jodrell, DI ; Sadler, PJ. / Tuning the reactivity of osmium(II) and ruthenium(II) arene complexes under physiological conditions. In: Journal of the American Chemical Society. 2006 ; Vol. 128, No. 5. pp. 1739-1748.

Bibtex

@article{1f05d9b1d9fd4835b4c21fc586f5cb1a,
title = "Tuning the reactivity of osmium(II) and ruthenium(II) arene complexes under physiological conditions",
abstract = "The Os-II arene ethylenediamine (en) complexes [(eta(6)-biphenyl)Os(en)Cl][Z], Z = BPh4 (4) and BF4 (5), are inactive toward A2780 ovarian cancer cells despite 4 being isostructural with an active Ru-II analogue, 4R. Hydrolysis of 5 occurred 40 times more slowly than 4R. The aqua adduct 5A has a low pK(a) (6.3) compared to that of [(eta(6)-biphenyl)Ru(en)(OH2)](2+) (7.7) and is therefore largely in the hydroxo form at physiological pH. The rate and extent of reaction of 5 with 9-ethylguanine were also less than those of 4R. We replaced the neutral en ligand by anionic acetylacetonate (acac). The complexes [(eta(6)-arene)Os(acac)Cl], arene = biphenyl (6), benzene (7), and p-cymene (8), adopt piano-stool structures similar to those of the Ru-II analogues and form weak dimers through intermolecular (arene)C-(HO)-O-...(acac) H-bonds. Remarkably, these Os-II acac complexes undergo rapid hydrolysis to produce not only the aqua adduct, [(eta(6)-arene)Os(acac)(OH2)](+), but also the hydroxo-bridged dimer, [(eta(6)-arene)Os(mu(2)-OH)(3) OS(eta(6)-arene)](+). The pK(a) values for the aqua adducts 6A, 7A, and 8A (7.1, 7.3, and 7.6, respectively) are lower than that for [(eta(6)-p-cymene)Ru(acac)(OH2)](+) (9.4). Complex 8A rapidly forms adducts with 9-ethylguanine and adenosine, but not with cytidine or thymidine. Despite their reactivity toward nucleobases, complexes 6-8 were inactive toward A549 lung cancer cells. This is attributable to rapid hydrolysis and formation of unreactive hydroxo-bridged dimers which, surprisingly, were the only species present in aqueous solution at biologically relevant concentrations. Hence, the choice of chelating ligand in Os-II (and Ru-II) arene complexes can have a dramatic effect on hydrolysis behavior and nucleobase binding and provides a means of tuning the reactivity and the potential for discovery of anticancer complexes.",
author = "Anna Peacock and A Habtemariam and R Fernandez and V Walland and FPA Fabbiani and S Parsons and RE Aird and DI Jodrell and PJ Sadler",
year = "2006",
month = feb
day = "8",
doi = "10.1021/ja055886r",
language = "English",
volume = "128",
pages = "1739--1748",
journal = "Journal of the American Chemical Society",
issn = "0002-7863",
publisher = "American Chemical Society",
number = "5",

}

RIS

TY - JOUR

T1 - Tuning the reactivity of osmium(II) and ruthenium(II) arene complexes under physiological conditions

AU - Peacock, Anna

AU - Habtemariam, A

AU - Fernandez, R

AU - Walland, V

AU - Fabbiani, FPA

AU - Parsons, S

AU - Aird, RE

AU - Jodrell, DI

AU - Sadler, PJ

PY - 2006/2/8

Y1 - 2006/2/8

N2 - The Os-II arene ethylenediamine (en) complexes [(eta(6)-biphenyl)Os(en)Cl][Z], Z = BPh4 (4) and BF4 (5), are inactive toward A2780 ovarian cancer cells despite 4 being isostructural with an active Ru-II analogue, 4R. Hydrolysis of 5 occurred 40 times more slowly than 4R. The aqua adduct 5A has a low pK(a) (6.3) compared to that of [(eta(6)-biphenyl)Ru(en)(OH2)](2+) (7.7) and is therefore largely in the hydroxo form at physiological pH. The rate and extent of reaction of 5 with 9-ethylguanine were also less than those of 4R. We replaced the neutral en ligand by anionic acetylacetonate (acac). The complexes [(eta(6)-arene)Os(acac)Cl], arene = biphenyl (6), benzene (7), and p-cymene (8), adopt piano-stool structures similar to those of the Ru-II analogues and form weak dimers through intermolecular (arene)C-(HO)-O-...(acac) H-bonds. Remarkably, these Os-II acac complexes undergo rapid hydrolysis to produce not only the aqua adduct, [(eta(6)-arene)Os(acac)(OH2)](+), but also the hydroxo-bridged dimer, [(eta(6)-arene)Os(mu(2)-OH)(3) OS(eta(6)-arene)](+). The pK(a) values for the aqua adducts 6A, 7A, and 8A (7.1, 7.3, and 7.6, respectively) are lower than that for [(eta(6)-p-cymene)Ru(acac)(OH2)](+) (9.4). Complex 8A rapidly forms adducts with 9-ethylguanine and adenosine, but not with cytidine or thymidine. Despite their reactivity toward nucleobases, complexes 6-8 were inactive toward A549 lung cancer cells. This is attributable to rapid hydrolysis and formation of unreactive hydroxo-bridged dimers which, surprisingly, were the only species present in aqueous solution at biologically relevant concentrations. Hence, the choice of chelating ligand in Os-II (and Ru-II) arene complexes can have a dramatic effect on hydrolysis behavior and nucleobase binding and provides a means of tuning the reactivity and the potential for discovery of anticancer complexes.

AB - The Os-II arene ethylenediamine (en) complexes [(eta(6)-biphenyl)Os(en)Cl][Z], Z = BPh4 (4) and BF4 (5), are inactive toward A2780 ovarian cancer cells despite 4 being isostructural with an active Ru-II analogue, 4R. Hydrolysis of 5 occurred 40 times more slowly than 4R. The aqua adduct 5A has a low pK(a) (6.3) compared to that of [(eta(6)-biphenyl)Ru(en)(OH2)](2+) (7.7) and is therefore largely in the hydroxo form at physiological pH. The rate and extent of reaction of 5 with 9-ethylguanine were also less than those of 4R. We replaced the neutral en ligand by anionic acetylacetonate (acac). The complexes [(eta(6)-arene)Os(acac)Cl], arene = biphenyl (6), benzene (7), and p-cymene (8), adopt piano-stool structures similar to those of the Ru-II analogues and form weak dimers through intermolecular (arene)C-(HO)-O-...(acac) H-bonds. Remarkably, these Os-II acac complexes undergo rapid hydrolysis to produce not only the aqua adduct, [(eta(6)-arene)Os(acac)(OH2)](+), but also the hydroxo-bridged dimer, [(eta(6)-arene)Os(mu(2)-OH)(3) OS(eta(6)-arene)](+). The pK(a) values for the aqua adducts 6A, 7A, and 8A (7.1, 7.3, and 7.6, respectively) are lower than that for [(eta(6)-p-cymene)Ru(acac)(OH2)](+) (9.4). Complex 8A rapidly forms adducts with 9-ethylguanine and adenosine, but not with cytidine or thymidine. Despite their reactivity toward nucleobases, complexes 6-8 were inactive toward A549 lung cancer cells. This is attributable to rapid hydrolysis and formation of unreactive hydroxo-bridged dimers which, surprisingly, were the only species present in aqueous solution at biologically relevant concentrations. Hence, the choice of chelating ligand in Os-II (and Ru-II) arene complexes can have a dramatic effect on hydrolysis behavior and nucleobase binding and provides a means of tuning the reactivity and the potential for discovery of anticancer complexes.

U2 - 10.1021/ja055886r

DO - 10.1021/ja055886r

M3 - Review article

C2 - 16448150

VL - 128

SP - 1739

EP - 1748

JO - Journal of the American Chemical Society

JF - Journal of the American Chemical Society

SN - 0002-7863

IS - 5

ER -