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Aiming to expand the structure\u2010activity relationships, seven new compounds were synthesized by incorporating isocyanide ligands: [Fe\n                    <jats:sub>2<\/jats:sub>\n                    Cp\n                    <jats:sub>2<\/jats:sub>\n                    (CO)(CNFc)(\u03bc\u2010CO){\u03bc\u2010CNMe(R)}]CF\n                    <jats:sub>3<\/jats:sub>\n                    SO\n                    <jats:sub>3<\/jats:sub>\n                    (Fc\u00a0= [Fe(Cp)(\u03b7\n                    <jats:sup>5<\/jats:sup>\n                    \u2010C\n                    <jats:sub>5<\/jats:sub>\n                    H\n                    <jats:sub>4<\/jats:sub>\n                    )], R\u00a0= Me,\n                    <jats:bold>2a<\/jats:bold>\n                    ; cyclohexyl\u00a0= Cy,\n                    <jats:bold>2b<\/jats:bold>\n                    ;\n                    <jats:italic>p<\/jats:italic>\n                    \u2010methoxyphenyl\u00a0= Anis,\n                    <jats:bold>2c<\/jats:bold>\n                    ; Cp\u00a0= \u03b7\n                    <jats:sup>5<\/jats:sup>\n                    \u2010C\n                    <jats:sub>5<\/jats:sub>\n                    H\n                    <jats:sub>5<\/jats:sub>\n                    ) and [Fe\n                    <jats:sub>2<\/jats:sub>\n                    Cp\n                    <jats:sub>2<\/jats:sub>\n                    (CO)\n                    <jats:sub>x<\/jats:sub>\n                    (CNR\u2032)\n                    <jats:sub>(1\u2010x)<\/jats:sub>\n                    (\u03bc\u2010CO){\u03bc\u2010CNMe(R)}]CF\n                    <jats:sub>3<\/jats:sub>\n                    SO\n                    <jats:sub>3<\/jats:sub>\n                    (R\u00a0= Cy, R\u2032\u00a0= Anis, x\u00a0= 1,\n                    <jats:bold>3b<\/jats:bold>\n                    or x\u00a0= 2,\n                    <jats:bold>4b<\/jats:bold>\n                    ; R\u00a0= Anis, R\u2032\u00a0= Cy, x\u00a0= 1,\n                    <jats:bold>3c<\/jats:bold>\n                    or x\u00a0= 2,\n                    <jats:bold>4c<\/jats:bold>\n                    ). The products were isolated in 70%\u201385% yields and characterized by IR, NMR spectroscopy, and single crystal X\u2010ray diffraction in one representative case. They display submillimolar water solubility, amphiphilic or moderately lipophilic character, and remarkable inertness in physiological\u2010like solutions. While the ferrocenyl derivatives\n                    <jats:bold>2a\u2013c<\/jats:bold>\n                    exhibited only modest activity,\n                    <jats:bold>3<\/jats:bold>\n                    and\n                    <jats:bold>4<\/jats:bold>\n                    displayed potent cytotoxicity across a panel of six cancer cell lines, with IC\n                    <jats:sub>50<\/jats:sub>\n                    values in the low micromolar range in most cases and in the nanomolar range for the NTERA\u20102 testis cell line. Moreover,\n                    <jats:bold>3b\u2013c<\/jats:bold>\n                    showed significant selectivity toward cancer cells and, along with\n                    <jats:bold>4b\u2013c<\/jats:bold>\n                    , retained a remarkable cytotoxic effect in 3D cell spheroids. Complexes\n                    <jats:bold>3b\u2013c<\/jats:bold>\n                    were effective in targeting cellular TrxR and increasing cellular ROS production.\n                  <\/jats:p>","DOI":"10.1002\/chem.202503129","type":"journal-article","created":{"date-parts":[[2026,1,25]],"date-time":"2026-01-25T07:24:05Z","timestamp":1769325845000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Isocyanide Incorporation Expands the Anticancer Potential of Diiron(I) Aminocarbyne Complexes"],"prefix":"10.1002","volume":"32","author":[{"given":"Chiara","family":"Saviozzi","sequence":"first","affiliation":[{"name":"Department of Chemistry and Industrial Chemistry University of Pisa  Pisa Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lorenzo","family":"Biancalana","sequence":"additional","affiliation":[{"name":"Department of Chemistry and Industrial Chemistry University of Pisa  Pisa 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