Although ferrocene derivatives have attracted considerable attention as possible anticancer agents, the medicinal potential of diiron complexes has remained largely unexplored. Herein, we describe the straightforward multigram‐scale synthesis and the antiproliferative activity of a series of diiron cyclopentadienyl complexes containing bridging vinyliminium ligands. IC50 values in the low‐to‐mid micromolar range were determined against cisplatin sensitive and resistant human ovarian carcinoma (A2780 and A2780cisR) cell lines. Notable selectivity towards the cancerous cells lines compared to the non‐tumoral human embryonic kidney (HEK‐293) cell line was observed for selected compounds. The activity seems to be multimodal, involving reactive oxygen species (ROS) generation and, in some cases, a fragmentation process to afford monoiron derivatives. The large structural variability, amphiphilic character and good stability in aqueous media of the diiron vinyliminium complexes provide favorable properties compared to other widely studied classes of iron‐based anticancer candidates.

The preparation of 24-functionalized 12,22:26,32-terpyridines (4′-functionalized 3,2:6′,3″-terpyridines) by the reaction of three 4-alkoxybenzaldehydes with 3-acetylpyridine and ammonia was investigated; under identical reaction conditions, two (R =nC4H9, C2H5) gave the expected products whereas a third (R = nC3H7) gave only a cyclohexanol derivative derived from the condensation of three molecules of 3-acetylpyridine with two of 4-(n-propoxy)benzaldehyde. A comprehensive survey of “unexpected” products from reactions of ArCOCH3 derivatives with aromatic aldehydes is presented. Three different types of alternative product are identified.

Five coordination polymers formed from combinations of copper(II) acetate and 4′-(4-alkyloxyphenyl)-3,2′:6′,3″-terpyridines with methoxy (1), n-butoxy (2), n-pentyloxy (3) and n-heptyloxy (4) substituents are reported. Reaction of 1 with Cu(OAc)2∙H2O leads to the 1D-polymer [Cu2(μ-OAc)4(1)]n in which {Cu2(μ-OAc)4} paddle-wheel units are connected by ligands 1, or [{Cu4(μ3-OH)2(μ-OAc)2(μ3-OAc)2(AcO-κO)2(1)2}·2MeOH]n in which centrosymmetric tetranuclear clusters link pairs of ligands 1 to give a double-stranded 1D-polymer. Layering solutions of Cu(OAc)2∙H2O (in MeOH) over 2, 3 or 4 (in CHCl3) leads to the assembly of the 1D-polymers [2{Cu2(μ-OAc)4(2)}·1.25MeOH]n, [Cu2(μ-OAc)4(3)]n and [{Cu2(μ-OAc)4(4)}·0.2CHCl3]n. In all compounds, the 3,2′:6′,3″-tpy unit coordinates only through the outer pyridine rings, but the conformation of the 3,2′:6′,3″-tpy responds to changes in the length of the alkyloxy tails leading to changes in the conformation of the polymer backbone and in the packing of the chains in the crystal lattice in the chains featuring {Cu2(μ-OAc)4} paddle-wheel linkers.

The synthesis and characterization of 4′-(4-n-propoxyphenyl)-3,2′:6′,3″-terpyridine is described. Five 2D-coordination networks have been isolated by crystal growth at room temperature from reactions of Co(NCS)2 with 4′-(4-n-alkyloxyphenyl)-3,2′:6′,3″-terpyridines in which the n-alkyl group is ethyl, n-propyl, n-butyl, n-pentyl and n-hexyl in ligands 2–6, respectively. The single-crystal structures of [{Co(2)2(NCS)2}.0.6CHCl3]n, [{Co(3)2(NCS)2}.4CHCl3.0.25H2O]n, [{Co(4)2(NCS)2}.4CHCl3]n, [Co2(5)4(NCS)4]n and [Co(6)2(NCS)2]n have been determined, and powder X-ray diffraction has demonstrated that the single-crystal structures are representative of the bulk materials. Each compound possesses a (4,4) net with Co centres as 4-connecting nodes. For the assemblies containing 2, 3 and 4, the (4,4) net comprises two geometrically different rhombuses, and the nets pack in an ABAB... arrangement with cone-like arrangements of n-alkyloxyphenyl groups being accommodated in a similar unit in an adjacent net. An increase in the n-alkyloxy chain length has two consequences: there is a change in the conformation of the 3,2′:6′,3″-tpy metal-binding domain, and the (4,4) net comprises identical rhombuses. Similarities and differences between the assemblies with ligands 2–6 and the previously reported [{Co(1)2(NCS)2}.3MeOH]n and [{Co(1)2(NCS)2}.2.2CHCl3]n in which 1 is 4′-(4-methoxyphenyl)-3,2′:6′,3″-terpyridine are discussed. The results demonstrate the effects of combining a variable chain length in the 4′-(4-n-alkyloxyphenyl) substituents of 3,2′:6′,3″-tpy and a conformationally flexible 3,2′:6′,3″-tpy metal-binding domain.

We report the preparation and characterization of 4′-([1,1′-biphenyl]-4-yl)-3,2′:6′,3″-terpyridine (1), 4′-(4′-fluoro-[1,1′-biphenyl]-4-yl)-3,2′:6′,3″-terpyridine (2), 4′-(4′-chloro-[1,1′-biphenyl]-4-yl)-3,2′:6′,3″-terpyridine (3), 4′-(4′-bromo-[1,1′-biphenyl]-4-yl)-3,2′:6′,3″-terpyridine (4), and 4′-(4′-methyl-[1,1′-biphenyl]-4-yl)-3,2′:6′,3″-terpyridine (5), and their reactions with copper(II) acetate. Single-crystal structures of the [Cu2(μ-OAc)4L]n 1D-coordination polymers with L = 1–5 have been determined, and powder X-ray diffraction confirms that the single crystal structures are representative of the bulk samples. [Cu2(μ-OAc)4(1)]n and [Cu2(μ-OAc)4(2)]n are isostructural, and zigzag polymer chains are present which engage in π-stacking interactions between [1,1′-biphenyl]pyridine units. 1D-chains nest into one another to give 2D-sheets; replacing the peripheral H in 1 by an F substituent in 2 has no effect on the solid-state structure, indicating that bifurcated contacts (H...H for 1 or H...F for 2) are only secondary packing interactions. Upon going from [Cu2(μ-OAc)4(1)]n and [Cu2(μ-OAc)4(2)]n to [Cu2(μ-OAc)4(3)]n, [Cu2(μ-OAc)4(4)]n, and [Cu2(μ-OAc)4(5)]n·nMeOH, the increased steric demands of the Cl, Br, or Me substituent induces a switch in the conformation of the 3,2′:6′,3″-tpy metal-binding domain, and a concomitant change in dominant packing interactions to py–py and py–biphenyl face-to-face π-stacking. The study underlines how the 3,2′:6′,3″-tpy domain can adapt to different steric demands of substituents through its conformational flexibility.

The synthesis and characterization of 4′-(4-methoxyphenyl)-3,2′:6′,3″-terpyridine (2) (IUPAC PIN 24-(4-methoxyphenyl)-12,22:26,32-terpyridine) are described, and its coordination behaviour with cobalt(II) thiocyanate has been investigated. In a series of experiments, crystals were grown at room temperature by layering a MeOH solution of Co(NCS)2 over a CHCl3 solution of 2 using 1:1, 1:2 or 2:1 molar ratios of metal salt-to-ligand. Crystals harvested within 2–3 weeks proved to be the 1D-coordination polymer [Co(2)(NCS)2(MeOH)2]n and powder X-ray diffraction (PXRD) confirmed that the crystals selected for single-crystal X-ray diffraction were representative of the bulk samples. Longer crystallization times with a Co(NCS)2 to 2 molar ratio of 1:1 yielded crystals of [Co(2)(NCS)2(MeOH)2]n (1D-chain) and the pseudopolymorphs [{Co(2)2(NCS)2}·3MeOH]n and [{Co(2)2(NCS)2}·2.2CHCl3]n ((4,4)-nets), each type of crystal originating from a different zone in the crystallization tube. PXRD for this last experiment confirmed that the dominant product in the bulk sample was the 1D-coordination polymer.

A series of diiron complexes with two cyclopentadienyls, two carbonyls, and one bridging vinyl-aminoalkylidene as ligands, [3a-h]CF 3 SO 3 and [4a-d] CF 3 SO 3 , was synthesized in 66-94% yields from diiron μ-aminocarbyne precursors. The subsequent reactions with pyrrolidine led to selective fragmentation to aminoalkylidene-ferracyclopentenone derivatives (5a-h and 6a-c) in 30-84% yields. The compounds were characterized by elemental analysis, Fourier transform infrared and NMR spectroscopy, and by single crystal X-ray diffraction in three cases. The stability in aqueous media relevant to biological trials, the carbon monoxide release, and the catalytic activity in NADH oxidation were evaluated for selected compounds by NMR spectroscopy and gas chromatography. The in vitro antiproliferative activity of the compounds was determined towards cancer (A2780, A2780cisR) and noncancer (HEK-293) cell lines. Moreover, the antibacterial activity was tested on Gram-positive (vancomycin-resistant E. faecium and methicillin-resistant S. aureus) and Gram-negative strains (A. baumannii and P. aeruginosa). K E Y W O R D S amino-alkylidene ligand, bioorganometallic chemistry, cytotoxic and antibacterial activity, diiron complexes, iron-carbonyl complexes Dalila Rocco and Natalia Busto contributed equally to the work.

The reaction of pyrrolidine with a series of cationic diiron cyclopentadienyl complexes containing a bridging vinyliminium ligand gives access to piano stool monoiron complexes based on a five-membered metallacycle that includes a vinyl-aminoalkylidene moiety, in moderate to high yields. The resulting metallacyclic motif (aminoalkylidene-ferracyclopentenone) is unique in organometallic chemistry and is partially preconstructed on the dinuclear frame. The monoiron products were fully characterized by elemental analysis, IR and multi-nuclear NMR spectroscopy, and in a number of cases by X-ray diffraction and cyclic voltammetry. They are robust in aqueous solutions and generally unreactive towards alkylating agents in organic solvents. However, a cationic derivative was prepared in high yield by methylation of a 2-pyridyl group. The cytotoxicity of both neutral and ionic complexes was assessed on cancerous (A2780 and A280cisR) and non-cancerous (HEK293) cell lines, revealing the influence of local structural modifications on the antiproliferative activity and the selectivity of the compounds.