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

The Os(II) arene ethylenediamine (en) complexes [(eta(6)-biphenyl)Os(en)Cl][Z], Z = BPh(4) (4) and BF(4) (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... Full description

Journal Title: Journal of the American Chemical Society February 8, 2006, Vol.128(5), pp.1739-1748
Main Author: Peacock, Anna F A
Other Authors: Habtemariam, Abraha , Fernández, Rafael , Walland, Victoria , Fabbiani, Francesca P A , Parsons, Simon , Aird, Rhona E , Jodrell, Duncan I , Sadler, Peter J
Format: Electronic Article Electronic Article
Language: English
Subjects:
ID: ISSN: 0002-7863
Link: http://search.proquest.com/docview/70722204/?pq-origsite=primo
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title: Tuning the reactivity of osmium(II) and ruthenium(II) arene complexes under physiological conditions.
format: Article
creator:
  • Peacock, Anna F A
  • Habtemariam, Abraha
  • Fernández, Rafael
  • Walland, Victoria
  • Fabbiani, Francesca P A
  • Parsons, Simon
  • Aird, Rhona E
  • Jodrell, Duncan I
  • Sadler, Peter J
subjects:
  • Antineoplastic Agents–Chemical Synthesis
  • Benzene Derivatives–Chemistry
  • Cell Line, Tumor–Pharmacology
  • Crystallography, X-Ray–Chemical Synthesis
  • Drug Screening Assays, Antitumor–Chemistry
  • Female–Pharmacology
  • Humans–Chemical Synthesis
  • Organometallic Compounds–Chemistry
  • Osmium–Pharmacology
  • Ovarian Neoplasms–Chemistry
  • Ruthenium–Drug Therapy
  • Ruthenium–Chemistry
  • Antineoplastic Agents
  • Benzene Derivatives
  • Organometallic Compounds
  • Osmium
  • Ruthenium
ispartof: Journal of the American Chemical Society, February 8, 2006, Vol.128(5), pp.1739-1748
description: The Os(II) arene ethylenediamine (en) complexes [(eta(6)-biphenyl)Os(en)Cl][Z], Z = BPh(4) (4) and BF(4) (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)(OH(2))](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-H...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)(OH(2))](+), 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)(OH(2))](+) (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.
language: eng
source:
identifier: ISSN: 0002-7863
fulltext: no_fulltext
issn:
  • 00027863
  • 0002-7863
url: Link


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titleTuning the reactivity of osmium(II) and ruthenium(II) arene complexes under physiological conditions.
creatorPeacock, Anna F A ; Habtemariam, Abraha ; Fernández, Rafael ; Walland, Victoria ; Fabbiani, Francesca P A ; Parsons, Simon ; Aird, Rhona E ; Jodrell, Duncan I ; Sadler, Peter J
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ispartofJournal of the American Chemical Society, February 8, 2006, Vol.128(5), pp.1739-1748
identifierISSN: 0002-7863
subjectAntineoplastic Agents–Chemical Synthesis ; Benzene Derivatives–Chemistry ; Cell Line, Tumor–Pharmacology ; Crystallography, X-Ray–Chemical Synthesis ; Drug Screening Assays, Antitumor–Chemistry ; Female–Pharmacology ; Humans–Chemical Synthesis ; Organometallic Compounds–Chemistry ; Osmium–Pharmacology ; Ovarian Neoplasms–Chemistry ; Ruthenium–Drug Therapy ; Ruthenium–Chemistry ; Antineoplastic Agents ; Benzene Derivatives ; Organometallic Compounds ; Osmium ; Ruthenium
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descriptionThe Os(II) arene ethylenediamine (en) complexes [(eta(6)-biphenyl)Os(en)Cl][Z], Z = BPh(4) (4) and BF(4) (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)(OH(2))](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-H...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)(OH(2))](+), 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)(OH(2))](+) (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.
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titleTuning the reactivity of osmium(II) and ruthenium(II) arene complexes under physiological conditions.
authorPeacock, Anna F A ; Habtemariam, Abraha ; Fernández, Rafael ; Walland, Victoria ; Fabbiani, Francesca P A ; Parsons, Simon ; Aird, Rhona E ; Jodrell, Duncan I ; Sadler, Peter J
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