Bicyclic [3]ferrocenophanes from reductive couplings of 1,1′-bis(2-acetylvinyl)ferrocene: synthesis, structure, electrochemistry and anti-cancer evaluation

The intramolecular McMurry reaction of a ferrocenyl 1,1′-bis( α , β -unsaturated ketone) proceeds with formation of two carbon‑carbon bonds between the side arms. As a result, chiral bicyclic [3]ferrocenophanes, with cyclopentadiene or cyclopentane rings fused with the bridge, have been formed. The isomeric cyclopentadienes (±)-2a and 2b , as well as cis -diol (±)-3 , were isolated and thoroughly characterized by means of 1 H and 13 C NMR spectroscopy, HR MS, single-crystal X-ray diffraction and cyclic voltammetry. The [3]ferrrocenophanes were tested for anti-cancer activity towards four cancer cell lines (MCF-7, MDA-MB-231, PC-3, K-562). The ( p -hydroxyphenyl)boronic acid ester (±)-4 , derived from diol (±)-3 , displays the highest activity in the micromolar range (31.3 μM, PC-3 cells, 27.3 μM, K-562 cells). Mitochondrial membrane potential studies with (±)-4 suggest its pro-apoptotic properties. • Bicyclic [3]ferrocenophanes are obtained using the McMurry reaction. • The bicyclic [3]ferrocenophanes display low ring tilt and rigid chiral structure. • Anti-cancer activity of [3]ferrocenophanes is investigated in four cell lines. • The most active [3]ferrocenophane has pro-apoptotic properties.