Iridium(III)-based minor groove binding complexes as DNA photocleavage agents


Transition metal complexes containing the qtpy ligand (2':4,4'':4',4'''-quaterpyridyl) are known to be DNA intercalators or minor groove binders. In this study, new tricationic iridium(III) complexes of qtpy are reported. Both [Ir(bpy) 2(qtpy)] 3+1 and [Ir(phen) 2(qtpy)] 3+2 display good water solubility as chloride salts. The complexes possess high-energy excited states, which are quenched in the presence of duplex DNA and even by the mononucleotides guanosine monophosphate and adenosine monophosphate. Further studies reveal that although the complexes bind to quadruplex DNA, they display a preference for duplex structures, which are bound with an order of magnitude higher affinities than their isostructural dicationic Ru II-analogues. Detailed molecular dynamics simulations confirm that the complexes are groove binders through the insertion of, predominantly, the qtpy ligand into the minor groove. Photoirradiation of 1 in the presence of plasmid DNA confirms that this class of complexes can function as synthetic photonucleases by cleaving DNA.

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Divisions: College of Health & Life Sciences > School of Biosciences
College of Health & Life Sciences
Funding Information: S. A. O. is grateful for the award of a University of Sheffield Research Scholarship. T. J. thanks Prof. Dr. Mark Bathe (MIT, Cambridge, MA, USA) for his mentorship and project funding. T. J. was supported by the National Science Foundation (NSF, CCF-1956
Additional Information: This article is licensed under aCreative Commons Attribution-NonCommercial 3.0 Unported Licence. Publisher Copyright: © 2024 The Royal Society of Chemistry.
Uncontrolled Keywords: Iridium/chemistry,DNA/chemistry,Coordination Complexes/chemistry,DNA Cleavage,Molecular Dynamics Simulation,Ligands,Molecular Structure
Publication ISSN: 1477-9234
Last Modified: 05 Jul 2024 07:13
Date Deposited: 02 May 2024 13:00
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Related URLs: ... 4/dt/d4dt00171k (Publisher URL)
http://www.scop ... tnerID=8YFLogxK (Scopus URL)
PURE Output Type: Article
Published Date: 2024-04-30
Accepted Date: 2024-03-04
Authors: Aderinto, Stephen O
John, Torsten
Onawole, Abdulmujeeb
Galleh, Raphael Peter (ORCID Profile 0000-0003-2541-4851)
Thomas, Jim A


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