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

Authors :
Aderinto SO
John T
Onawole A
Galleh RP
Thomas JA
Source :
Dalton transactions (Cambridge, England : 2003) [Dalton Trans] 2024 Apr 30; Vol. 53 (17), pp. 7282-7291. Date of Electronic Publication: 2024 Apr 30.
Publication Year :
2024

Abstract

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) <subscript>2</subscript> (qtpy)] <superscript>3+</superscript> 1 and [Ir(phen) <subscript>2</subscript> (qtpy)] <superscript>3+</superscript> 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 <superscript>II</superscript> -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.

Details

Language :
English
ISSN :
1477-9234
Volume :
53
Issue :
17
Database :
MEDLINE
Journal :
Dalton transactions (Cambridge, England : 2003)
Publication Type :
Academic Journal
Accession number :
38466178
Full Text :
https://doi.org/10.1039/d4dt00171k