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Our group has previously identified metal-based compounds, [Ag(1,10-phenanthroline-5,6-dione)<jats:sub>2<\/jats:sub>]ClO<jats:sub>4<\/jats:sub>(Ag-phendione) and [Cu(1,10-phenanthroline-5,6-dione)<jats:sub>3<\/jats:sub>](ClO<jats:sub>4<\/jats:sub>)<jats:sub>2<\/jats:sub>.4H<jats:sub>2<\/jats:sub>O (Cu-phendione), with efficient antimicrobial action against multidrug-resistant species. Herein, we investigated the ability of Ag-phendione and Cu-phendione to bind with double-stranded DNA using a combination of in silico and in vitro approaches. Molecular docking revealed that both phendione derivatives can interact with the DNA by hydrogen bonding, hydrophobic and electrostatic interactions. Cu-phendione exhibited the highest binding affinity to either major (\u2212\u00a07.9\u00a0kcal\/mol) or minor (\u2212\u00a07.2\u00a0kcal\/mol) DNA grooves. In vitro competitive quenching assays involving duplex DNA with Hoechst 33258 or ethidium bromide demonstrated that Ag-phendione and Cu-phendione preferentially bind DNA in the minor grooves. The competitive ethidium bromide displacement technique revealed Cu-phendione has a higher binding affinity to DNA (<jats:italic>K<\/jats:italic><jats:sub>app<\/jats:sub>\u2009=\u20092.55\u2009\u00d7\u200910<jats:sup>6<\/jats:sup>\u00a0M<jats:sup>\u22121<\/jats:sup>) than Ag-phendione (<jats:italic>K<\/jats:italic><jats:sub>app<\/jats:sub>\u2009=\u20092.79\u2009\u00d7\u200910<jats:sup>5<\/jats:sup>\u00a0M<jats:sup>\u22121<\/jats:sup>) and phendione (<jats:italic>K<\/jats:italic><jats:sub>app<\/jats:sub>\u2009=\u20091.33\u2009\u00d7\u200910<jats:sup>5<\/jats:sup>\u00a0M<jats:sup>\u22121<\/jats:sup>). Cu-phendione induced topoisomerase I-mediated DNA relaxation of supercoiled plasmid DNA. Moreover, Cu-phendione was able to induce oxidative DNA injuries with the addition of free radical scavengers inhibiting DNA damage. Ag-phendione and Cu-phendione avidly displaced propidium iodide bound to DNA in permeabilized<jats:italic>Pseudomonas aeruginosa<\/jats:italic>cells in a dose-dependent manner as judged by flow cytometry. The treatment of<jats:italic>P. aeruginosa<\/jats:italic>with bactericidal concentrations of Cu-phendione (15\u00a0\u00b5M) induced DNA fragmentation as visualized by either agarose gel or TUNEL assays. Altogether, these results highlight a possible novel DNA-targeted mechanism by which phendione-containing complexes, in part, elicit toxicity toward the multidrug-resistant pathogen<jats:italic>P. aeruginosa<\/jats:italic>.<\/jats:p><jats:p><jats:bold>Graphical abstract<\/jats:bold><\/jats:p>","DOI":"10.1007\/s00775-021-01922-3","type":"journal-article","created":{"date-parts":[[2022,1,10]],"date-time":"2022-01-10T12:04:03Z","timestamp":1641816243000},"page":"201-213","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":24,"title":["Copper(II) and silver(I)-1,10-phenanthroline-5,6-dione complexes interact with double-stranded DNA: further evidence of their apparent multi-modal activity towards Pseudomonas aeruginosa"],"prefix":"10.1007","volume":"27","author":[{"given":"Anna Clara Milesi","family":"Galdino","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"L\u00edvia","family":"Viganor","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matheus Mendon\u00e7a","family":"Pereira","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Devereux","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Malachy","family":"McCann","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marta Helena","family":"Branquinha","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zara","family":"Molphy","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sin\u00e9ad","family":"O\u2019Carroll","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Conor","family":"Bain","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Georgia","family":"Menounou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew","family":"Kellett","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andr\u00e9 Luis Souza","family":"dos Santos","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2022,1,10]]},"reference":[{"key":"1922_CR1","doi-asserted-by":"publisher","first-page":"142","DOI":"10.1016\/j.ejmech.2019.04.032","volume":"174","author":"DK Mahapatra","year":"2019","unstructured":"Mahapatra DK, Bharti SK, Asati V et al (2019) Perspectives of medicinally privileged chalcone based metal coordination compounds for biomedical applications. 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