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Here, a new type of AMN combining a tris\u2010(2\u2010pyridylmethyl)amine (TPMA) scaffold with the copper(II) <jats:italic>N<\/jats:italic>,<jats:italic>N\u2032<\/jats:italic>\u2010phenanthrene chemical nuclease core is reported. In designing these complexes, the stabilization and flexibility of TPMA together with the prominent chemical nuclease activity of copper 1,10\u2010phenanthroline (Phen) were targeted. A second aspect was the opportunity to introduce designer phenazine DNA intercalators (e.g., dipyridophenazine; DPPZ) for improved DNA recognition. Five compounds of formula [Cu(TPMA)(<jats:italic>N<\/jats:italic>,<jats:italic>N<\/jats:italic>\u2032)]<jats:sup>2+<\/jats:sup> (where <jats:italic>N<\/jats:italic>,<jats:italic>N<\/jats:italic>\u2032 is 2,2\u2010bipyridine (Bipy), Phen, 1,10\u2010phenanthroline\u20105,6\u2010dione (PD), dipyridoquinoxaline (DPQ), or dipyridophenazine (DPPZ)) were developed and characterized by X\u2010ray crystallography. Solution stabilities were studied by continuous\u2010wave EPR (cw\u2010EPR), hyperfine sublevel correlation (HYSCORE), and Davies electron\u2013nuclear double resonance (ENDOR) spectroscopies, which demonstrated preferred geometries in which phenanthrene ligands were coordinated to the copper(II) TPMA core. Complexes with Phen, DPQ, and DPPZ ligands possessed enhanced DNA binding activity, with DPQ and DPPZ compounds showing excellent intercalative effects. These complexes are effective AMNs and analysis with spin\u2010trapping scavengers of reactive oxygen species and DNA repair enzymes with glycosylase\/endonuclease activity demonstrated a distinctive DNA oxidation activity compared to classical Sigman\u2010 and Fenton\u2010type reagents.<\/jats:p>","DOI":"10.1002\/chem.201804084","type":"journal-article","created":{"date-parts":[[2018,9,17]],"date-time":"2018-09-17T06:15:09Z","timestamp":1537164909000},"page":"221-237","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":38,"title":["Polypyridyl\u2010Based Copper Phenanthrene Complexes: A New Type of Stabilized Artificial Chemical Nuclease"],"prefix":"10.1002","volume":"25","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3161-0656","authenticated-orcid":false,"given":"Nicol\u00f3","family":"Zuin\u2005Fantoni","sequence":"first","affiliation":[{"name":"School of Chemical Sciences and National Institute for Cellular, Biotechnology Dublin City University  9 Glasnevin, Dublin Ireland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9717-6130","authenticated-orcid":false,"given":"Zara","family":"Molphy","sequence":"additional","affiliation":[{"name":"School of Chemical Sciences and National Institute for Cellular, Biotechnology Dublin City University  9 Glasnevin, Dublin Ireland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1778-5217","authenticated-orcid":false,"given":"Creina","family":"Slator","sequence":"additional","affiliation":[{"name":"School of Chemical Sciences and National Institute for Cellular, Biotechnology Dublin City University  9 Glasnevin, Dublin Ireland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2195-6787","authenticated-orcid":false,"given":"Georgia","family":"Menounou","sequence":"additional","affiliation":[{"name":"ISOF-CNR Area della Ricerca di Bologna  Via P. 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