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Here, we demonstrate how the 1,2,3\u2010triazole linker produced by the Cu\u2010catalysed azide\u2010alkyne cycloaddition (CuAAC) reaction can be directed to build Cu\u2010binding AMN scaffolds. We selected biologically inert reaction partners\n                    <jats:italic>tris<\/jats:italic>\n                    (azidomethyl)mesitylene and ethynyl\u2010thiophene to develop TC\u2010Thio, a bioactive\n                    <jats:italic>C<\/jats:italic>\n                    <jats:sub>3<\/jats:sub>\n                    \u2010symmetric ligand in which three thiophene\u2010triazole moieties are positioned around a central mesitylene core. The ligand was characterised by X\u2010ray crystallography and forms multinuclear Cu\n                    <jats:sup>II<\/jats:sup>\n                    and Cu\n                    <jats:sup>I<\/jats:sup>\n                    complexes identified by mass spectrometry and rationalised by density functional theory (DFT). Upon Cu coordination, Cu\n                    <jats:sup>II<\/jats:sup>\n                    \u2010TC\u2010Thio becomes a potent DNA binding and cleaving agent. Mechanistic studies reveal DNA recognition occurs exclusively at the minor groove with subsequent oxidative damage promoted through a superoxide\u2010 and peroxide\u2010dependent pathway. Single molecule imaging of DNA isolated from peripheral blood mononuclear cells shows that the complex has comparable activity to the clinical drug temozolomide, causing DNA damage that is recognised by a combination of base excision repair (BER) enzymes.\n                  <\/jats:p>","DOI":"10.1002\/anie.202305759","type":"journal-article","created":{"date-parts":[[2023,6,20]],"date-time":"2023-06-20T08:00:48Z","timestamp":1687248048000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":16,"title":["A Click Chemistry\u2010Based Artificial Metallo\u2010Nuclease"],"prefix":"10.1002","volume":"62","author":[{"given":"Alex","family":"Gibney","sequence":"first","affiliation":[{"name":"SSPC, the Science Foundation Ireland Research Centre for Pharmaceuticals School of Chemical Sciences Dublin City University  Glasnevin Dublin 9 Dublin Ireland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Raphael E. 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