The Library
Organometallic iridium(III) cyclopentadienyl anticancer complexes containing C,N-chelating ligands
Tools
Liu, Zhe , Habtemariam, Abraha, Pizarro, Ana M., Clarkson, Guy J. and Sadler, P. J. (2011) Organometallic iridium(III) cyclopentadienyl anticancer complexes containing C,N-chelating ligands. Organometallics, Vol.30 (No.17). pp. 4702-4710. doi:10.1021/om2005468 ISSN 0276-7333.
|
Text
WRAP_Sadler_180811-15_sadler_om2011-005468.pdf - Accepted Version Download (851Kb) |
Official URL: http://dx.doi.org/10.1021/om2005468
Abstract
Organometallic IrIII cyclopentadienyl complexes [(η5-Cpx)Ir(CN)Cl] {Cpx = Cp*, CN = 2-(p-tolyl)pyridine (1), 2-phenylquinoline (2), 2-(2,4-difluorophenyl)pyridine (3), Cpx = tetramethyl(phenyl)cyclopentadienyl (Cpxph), CN = 2-phenylpyridine (4), and Cpx = tetramethyl(biphenyl)cyclopentadienyl (Cpxbiph), CN = 2-phenylpyridine (5)} have been synthesized and characterized. The X-ray crystal structures of 2 and 5 have been determined and show typical “piano-stool” geometry. All the complexes hydrolyzed rapidly in aqueous solution (<5 min) even at 278 K. The pKa values of the aqua adducts 1A–5A are in the range 8.31–8.87 and follow the order 1A > 2A > 4A > 5A ≈ 3A. Hydroxo-bridged dimers {[(η5-Cpx)Ir]2(μ-OD)3}+ (Cpx = Cp*, 6; Cpxph, 7; Cpxbiph, 8) are readily formed during pH titrations at ca. pH 8.7. Complexes 1 and 3–5 bind strongly to 9-ethylguanine (9-EtG), moderately strongly to 9-methyladenine (9-MeA), and hence preferentially to 9-EtG when in competition with 9-MeA. The extent of guanine and adenine binding to complex 2 was significantly lower for both purines due to steric hindrance from the chelating ligand. All complexes showed potent cytotoxicity, with IC50 values ranging from 6.5 to 0.7 μM toward A2780 human ovarian cancer cells. Potency toward these cancer cells increased with additional phenyl substitution on Cp*: Cpxbiph > Cpxph > Cp*. Cpxbiph with complex 5 exhibited submicromolar activity (2× as active as cisplatin). These data demonstrate how the aqueous chemistry, nucleobase binding, and anticancer activity of C,N-bound IrIII cyclopentadienyl complexes can be controlled and fine-tuned by the modification of the chelating and cyclopentadienyl ligands.
Item Type: | Journal Article | ||||
---|---|---|---|---|---|
Subjects: | Q Science > QD Chemistry | ||||
Divisions: | Faculty of Science, Engineering and Medicine > Science > Chemistry | ||||
Library of Congress Subject Headings (LCSH): | Organoiridium compounds, Antineoplastic agents, Ovaries -- Cancer -- Treatment | ||||
Journal or Publication Title: | Organometallics | ||||
Publisher: | American Chemical Society | ||||
ISSN: | 0276-7333 | ||||
Official Date: | 5 August 2011 | ||||
Dates: |
|
||||
Volume: | Vol.30 | ||||
Number: | No.17 | ||||
Page Range: | pp. 4702-4710 | ||||
DOI: | 10.1021/om2005468 | ||||
Status: | Peer Reviewed | ||||
Access rights to Published version: | Restricted or Subscription Access | ||||
Date of first compliant deposit: | 17 December 2015 | ||||
Date of first compliant Open Access: | 17 December 2015 | ||||
Funder: | University of Warwick, European Research Council (ERC), Engineering and Physical Sciences Research Council (EPSRC), Overseas Research Students Awards Scheme (ORSAS), European Regional Development Fund (ERDF), Advantage West Midlands (AWM), Birmingham Science City | ||||
Grant number: | 247450 (ERC) |
Data sourced from Thomson Reuters' Web of Knowledge
Request changes or add full text files to a record
Repository staff actions (login required)
View Item |
Downloads
Downloads per month over past year