Adding Diversity to a Diruthenium Biscyclopentadienyl Scaffold via Alkyne Incorporation: Synthesis and Biological Studies

Abstract

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 exchangeProtonation of 1−3 by HBF 4 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 Ru 2 Cp 2 (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.

Synthesis and studies of aqueous-stable diruthenium aminocarbyne complexes uncovered an N-indolyl derivative as a prospective anticancer agent

“…We provide a rare electrochemical description of diruthenium bis-cyclopentadienyl compounds. 36,37,62…”

“…73,74 Complex [ 2d ] + exerts a generally more potent antiproliferative effect compared to other cationic complexes based on the Ru 2 Cp 2 (CO) 3 scaffold, under analogous conditions. 36,37 We hypothesize that the higher performance of [ 2d ] + is consequent to its greater aqueous stability.…”

“…Contributing to this field, we have recently unveiled the activity of [Ru 2 Cp 2 (CO) 4 ] derivatives containing bridging allenyl 36 and vinyl ligands. 37…”

Anticancer Potential of Diruthenium Complexes with Bridging Hydrocarbyl Ligands from Bioactive Alkynols

“…We synthesized the diruthenacyclopentenone complex 1 using a recently published procedure, starting from commercial [Ru 2 Cp 2 (CO) 4 ] . It has been established that the {PhCCPh} fragment within 1 is susceptible to thermal exchange with a variety of alkynes. ,, Specifically, there is documented evidence that the reactions between 1 and propargyl alcohols of formula HCCCRR′OH (RR′ = HH, MeMe, MePh) are regioselective, i.e., the CRR’OH unit in the diruthenacyclopentenone products is placed far from the Cp rings. − Then, addition of a strong protonating agent leads to cationic complexes with a bridging allenyl ligand, via H 2 O elimination. − , We exploited this strategy to conjugate 17α-ethynylestradiol and 17-ethynyltestosterone with the {Ru 2 Cp 2 (CO) 3 } scaffold (Scheme ). Thus, the reactions of 1 with an excess of such two alkynes and 1-ethynylcyclopentanol, which was used as a nonbioactive analog, were carried out in toluene solution under reflux conditions.…”

Mixed valence triiron complexes from the conjugation of [FeIFeI] and [FeII] complexes via intermolecular carbyne/alkyne coupling

“…Another widely employed strategy, for assembling homo- and heteronuclear organometallic compounds, involves coordinating a pendent alkyne group from a monometallic complex to a second metal center or cluster. 17–21 On the other hand, while insertion reactions of alkynes into metal–ligand units are rather common in organometallic chemistry, 22–27 the alkyne insertion approach has been barely explored for increasing the nuclearity of metallic structures. A relevant exception regards iron-platinum dimetallacyclopentenone complexes with an alkyne pendant, which was incorporated within a second [FePt] scaffold through insertion into the Pt-(μ-CO) bond.…”