Diiron Complexes with a Bridging Functionalized Allylidene Ligand: Synthesis, Structural Aspects, and Cytotoxicity

Abstract

Regio-and stereo-selective nucleophilic attack of cyanide (from NBu 4 CN) to cationic diironaffords nitrile-aminoallylidene derivatives, 2a-f, in good to excellent yield. The analogous reaction of [1g]CF 3 SO 3 , comprising two different N-substituents, gives 4 (63%) as a mixture of two stereoisomers.The new products [1g]CF 3 SO 3 , 2a-f and 4 were characterized by IR and NMR spectroscopy, and in a number of cases by IR-spectroelectrochemistry and single crystal X-ray diffraction. The allylidene complexes are air-stable and robust in aqueous solution, however, in general they undergo oxidation within a biologically relevant range of potentials. DFT calculations were carried out to rationalize the observed stereo-selectivity of the synthesis reaction and other structural and thermodynamic aspects.The cytotoxicity of 2a-f was assessed on cisplatin sensitive and resistant human ovarian carcinoma (A2780 and A2780cisR) cell lines, and human embryonic kidney (HEK-293) cells. Experiments reveal that treatment with the compounds leads to ROS production, with an absence of direct interactions with double stranded DNA (calf thymus) and bovine serum albumin.

Anticancer Diiron Vinyliminium Complexes: A Structure–Activity Relationship Study

“…Such a mode of action strikingly differs from that of platinum compounds, which instead induce cell death through DNA binding [ 10 , 30 ]. On the wave of our longtime experience with organo-iron synthetic chemistry [ 31 , 32 , 33 , 34 , 35 ], in the very last years we have contributed to unveil the anticancer potential of diiron complexes, which was almost unexplored [ 36 , 37 , 38 , 39 , 40 ]. This is surprising, in that diiron complexes hold a major advantage, compared to related monoiron species, due to the presence of adjacent metal atoms “working in concert”, thus allowing the easy construction and the stabilization of uncommon bridging ligands and the co-presence of other ligands [ 31 , 41 , 42 , 43 ].…”

“…Cationic complexes of type III ( Figure 1 ), containing a tightly coordinated bridging vinyliminium ligand, originate from the stepwise coupling of one isocyanide with one alkyne [ 44 ]. Complexes III are rather stable in aqueous media and display a variable cytotoxicity, ranging from the micromolar range to inactivity; they appear to exert their action following the general behavior shown by cytotoxic iron compounds, i.e., through the interference with redox processes [ 36 , 37 , 38 , 39 , 40 , 45 ]. Notwithstanding, other ways that are not accessible to ferrocene derivatives might be viable, including binding to biological targets [ 36 , 37 , 38 , 39 ] and the auxiliary effect of slow carbon monoxide release [ 37 , 40 , 45 ].…”

A Strategy to Conjugate Bioactive Fragments to Cytotoxic Diiron Bis(cyclopentadienyl) Complexes

“…Antiproliferative activity is maintained in neutral derivatives containing a modified vinyliminium chain. 14 …”

Construction of a Functionalized Selenophene‐Allylidene Ligand via Alkyne Double Action at a Diiron Complex

“…It should be noted that allylidene ligands bridging two metal centres in a µ‐η 1 :η 3 fashion are not uncommon in organometallic chemistry, being previously described also in analogous complexes based on the [M 2 Cp 2 (CO)(µ‐CO)] scaffold (M = Fe or Ru). However, such ligands typically consist of a hydrocarbyl C 3 chain, bearing only a limited degree of functionalization in some cases . In 6a , Fe(1) is σ‐coordinated to C(7) [Fe(1)–C(7) 1.948(5) Å], whereas Fe(2) is coordinated to all three carbon atoms constituting the η 3 ‐allylidene unit, i.e.…”