{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,28]],"date-time":"2026-04-28T22:35:45Z","timestamp":1777415745395,"version":"3.51.4"},"reference-count":47,"publisher":"MDPI AG","issue":"23","license":[{"start":{"date-parts":[[2019,11,26]],"date-time":"2019-11-26T00:00:00Z","timestamp":1574726400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001602","name":"Science Foundation Ireland","doi-asserted-by":"publisher","award":["12\/RC\/2275_P2"],"award-info":[{"award-number":["12\/RC\/2275_P2"]}],"id":[{"id":"10.13039\/501100001602","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>Herein, we report the synthesis, characterisation, X-ray crystallography, and oxidative DNA binding interactions of the copper artificial metallo-nuclease [Cu(DPQ)2(NO3)](NO3), where DPQ = dipyrido[3,2-f:2\u2032,3\u2032-h]quinoxaline. The cation [Cu(DPQ)2]2+ (Cu-DPQ), is a high-affinity binder of duplex DNA and presents an intercalative profile in topoisomerase unwinding and viscosity experiments. Artificial metallo-nuclease activity occurs in the absence of exogenous reductant but is greatly enhanced by the presence of the reductant Na-L-ascorbate. Mechanistically, oxidative DNA damage occurs in the minor groove, is mediated aerobically by the Cu(I) complex and is dependent on both superoxide and hydroxyl radical generation. To corroborate cleavage at the minor groove, DNA oxidation of a cytosine\u2013guanine (5\u2032-CCGG-3\u2032)-rich oligomer was examined in tandem with a 5-methylcytosine (5\u2032-C5mCGG-3\u2032) derivative where 5mC served to sterically block the major groove and direct damage to the minor groove. Overall, both the DNA binding affinity and cleavage mechanism of Cu-DPQ depart from Sigman\u2019s reagent [Cu(1,10-phenanthroline)2]2+; however, both complexes are potent oxidants of the minor groove.<\/jats:p>","DOI":"10.3390\/molecules24234301","type":"journal-article","created":{"date-parts":[[2019,11,26]],"date-time":"2019-11-26T10:57:27Z","timestamp":1574765847000},"page":"4301","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Copper bis-Dipyridoquinoxaline Is a Potent DNA Intercalator that Induces Superoxide-Mediated Cleavage via the Minor Groove"],"prefix":"10.3390","volume":"24","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9717-6130","authenticated-orcid":false,"given":"Zara","family":"Molphy","sequence":"first","affiliation":[{"name":"School of Chemical Sciences, National Institute for Cellular Biotechnology and Nano Research Facility, Dublin City University, Glasnevin, Dublin 9, Ireland"},{"name":"Synthesis and Solid-State Pharmaceutical Centre, School of Chemical Sciences, Dublin City University, Glasnevin, Dublin 9, Ireland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Vickie","family":"McKee","sequence":"additional","affiliation":[{"name":"School of Chemical Sciences, National Institute for Cellular Biotechnology and Nano Research Facility, Dublin City University, Glasnevin, Dublin 9, Ireland"},{"name":"Department of Physics, Chemistry and Pharmacy, University of Southern Denmark, Campusvej 55, 5230 Odense M, Denmark"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8947-1401","authenticated-orcid":false,"given":"Andrew","family":"Kellett","sequence":"additional","affiliation":[{"name":"School of Chemical Sciences, National Institute for Cellular Biotechnology and Nano Research Facility, Dublin City University, Glasnevin, Dublin 9, Ireland"},{"name":"Synthesis and Solid-State Pharmaceutical Centre, School of Chemical Sciences, Dublin City University, Glasnevin, Dublin 9, Ireland"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2019,11,26]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"12269","DOI":"10.1016\/S0021-9258(19)86305-6","article-title":"Oxygen-dependent cleavage of DNA by the 1,10-phenathroline cuporous complex. 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