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<title>Adding Diversity to a Diruthenium Biscyclopentadienyl Scaffold via Alkyne Incorporation: Synthesis and Biological Studies</title>
<creator>Bresciani, Giulio</creator>
<creator>Boni, Serena</creator>
<creator>Funaioli, Tiziana</creator>
<creator>Zacchini, Stefano</creator>
<creator>Pampaloni, Guido</creator>
<creator>Busto Vázquez, Natalia</creator>
<creator>Biver, Tarita</creator>
<creator>Marchetti, Fabio</creator>
<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.</description>
<date>2026-02-16</date>
<date>2026-02-16</date>
<date>2023-08</date>
<type>info:eu-repo/semantics/article</type>
<identifier>0020-1669</identifier>
<identifier>https://hdl.handle.net/10259/11370</identifier>
<identifier>10.1021/acs.inorgchem.3c01644</identifier>
<identifier>1520-510X</identifier>
<language>eng</language>
<relation>Inorganic Chemistry. 2023, V. 62, n. 31, p. 12453–12467</relation>
<relation>https://doi.org/10.1021/acs.inorgchem.3c01644</relation>
<rights>http://creativecommons.org/licenses/by/4.0/</rights>
<rights>info:eu-repo/semantics/openAccess</rights>
<rights>Atribución 4.0 Internacional</rights>
<publisher>American Chemical Society</publisher>
</thesis></metadata></record></GetRecord></OAI-PMH>