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<dc:title>Adding Diversity to a Diruthenium Biscyclopentadienyl Scaffold via Alkyne Incorporation: Synthesis and Biological Studies</dc:title>
<dc:creator>Bresciani, Giulio</dc:creator>
<dc:creator>Boni, Serena</dc:creator>
<dc:creator>Funaioli, Tiziana</dc:creator>
<dc:creator>Zacchini, Stefano</dc:creator>
<dc:creator>Pampaloni, Guido</dc:creator>
<dc:creator>Busto Vázquez, Natalia</dc:creator>
<dc:creator>Biver, Tarita</dc:creator>
<dc:creator>Marchetti, Fabio</dc:creator>
<dc:description>We report the synthesis and the assessment of the anticancer potential of two series of diruthenium biscyclopentadienyl carbonyl complexes. Novel dimetallacyclopentenone compounds (2–4) were obtained (45–92% yields) from the thermal reaction (PhCCPh exchange) of [Ru2Cp2(CO)(μ-CO){μ-η1:η3-C(Ph)═C(Ph)C(═O)}], 1, with alkynes HCCR [R = C5H4FeCp (Fc), 3-C6H4(Asp), 2-naphthyl; Cp = η5-C5H5, Asp = OC(O)-2-C6H4C(O)Me]. Protonation of 1–3 by HBF4 afforded the corresponding μ-alkenyl derivatives 5–7, in 40–86% yields. All products were characterized by IR and NMR spectroscopy; moreover, cyclic voltammetry (1, 2, 5, 7) and single-crystal X-ray diffraction (5, 7) analyses were performed on representative compounds. Complexes 5–7 revealed a cytotoxic activity comparable to that of cisplatin in A549 (lung adenocarcinoma), SW480 (colon adenocarcinoma), and ovarian (A2780) cancer cell lines, and 2, 5, 6, and 7 overcame cisplatin resistance in A2780cis cells. Complexes 2, 5, and 7 (but not the aspirin derivative 6) induced an increase in intracellular ROS levels. Otherwise, 6 strongly stabilizes and elongates natural DNA (from calf thymus, CT-DNA), suggesting a possible intercalation binding mode, whereas 5 is less effective in binding CT-DNA, and 7 is ineffective. This trend is reversed concerning RNA, and in particular, 7 is able to bind poly(rA)poly(rU) showing selectivity for this nucleic acid. Complexes 5–7 can interact with the albumin protein with a thermodynamic signature dominated by hydrophobic interactions. Overall, we show that organometallic species based on the Ru2Cp2(CO)x scaffold (x = 2, 3) are active against cancer cells, with different incorporated fragments influencing the interactions with nucleic acids and the production of ROS.</dc:description>
<dc:date>2026-02-16T16:52:26Z</dc:date>
<dc:date>2026-02-16T16:52:26Z</dc:date>
<dc:date>2023-08</dc:date>
<dc:type>info:eu-repo/semantics/article</dc:type>
<dc:identifier>0020-1669</dc:identifier>
<dc:identifier>https://hdl.handle.net/10259/11370</dc:identifier>
<dc:identifier>10.1021/acs.inorgchem.3c01644</dc:identifier>
<dc:identifier>1520-510X</dc:identifier>
<dc:language>eng</dc:language>
<dc:relation>Inorganic Chemistry. 2023, V. 62, n. 31, p. 12453–12467</dc:relation>
<dc:relation>https://doi.org/10.1021/acs.inorgchem.3c01644</dc:relation>
<dc:rights>http://creativecommons.org/licenses/by/4.0/</dc:rights>
<dc:rights>info:eu-repo/semantics/openAccess</dc:rights>
<dc:rights>Atribución 4.0 Internacional</dc:rights>
<dc:publisher>American Chemical Society</dc:publisher>
</ow:Publication>
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