Ferrocenyl Derivatives Research Articles

Organometallic Chalcones Functioning as Radical Traps: Observations on the Solvated Electron Reduction and the C·H2OH and C·H2Cl Addition Processes. A Time-Resolved, Mechanistic Study.

The pulse radiolysis method was used to investigate reactions between organometallic chalcones derived from ferrocene, cyrhetrene, and cymantrene substituted with a phenyl (R1) or a 4'-benzo-15-crown-5 (B1) moiety and the solvated electron e-sol and two radicals. The principal spectroscopic transformations resolved with the e-sol reactions reveal that the chalcone compounds react under a diffusion controlled condition. The chromophore in the reaction product is the radical anion chalcone, -C(═O)CH═CH-. The kinetics of the redox processes are consistent with the formation of the radical anion in a first step, followed by an E/Z isomerization reaction in the second step. The rate of the E/Z isomerization reaction is dependent on the chalcone substituent. Reactions with C·H2OH and C·H2Cl radicals are strongly affected by the nature of the organometallic fragment. The transient spectra for the reactions between C·H2OH and C·H2Cl radicals with the phenyl-substituted chalcone show weak, broad absorption bands at λob < 400 nm. Only the ferrocenyl derivatives showed an intense absorption band with λmax = 350 nm. The C-centered radicals react with organometallic chalcones with lifetimes less than or equal to a few microseconds, and the products are assigned as adducts of the C-centered radicals to the chalcone.

Synthesis, Characterization, and Biological Activity of Ferrocenyl Analogues of the Anthelmintic Drug Monepantel

There is major demand for the development of structurally new anti-infectives using innovative approaches to circumvent multidrug resistance in parasites. Herein, we describe the synthesis and characterization of ferrocenyl precursors and derivatives (2–8) of an anthelmintic drug, monepantel. All compounds were isolated as their racemates and characterized by 1H, 13C, and 19F NMR spectroscopy, mass spectrometry, and IR spectroscopy. The purity of individual compounds was confirmed by elemental microanalysis. The molecular structures of three of the organometallic compounds (5–7) were also established by X-ray crystallography. The biological activities of these compounds were then evaluated in vitro on various important eukaryotic parasites, including H. contortus, T. colubriformis, and D. immitis. The potencies against D. immitis (canine heartworm) of two compounds, a ferrocene-containing precursor (4) and the final ferrocene-based monepantel derivative (8), were shown to be moderate (EC50 = 3.70 μg/mL fo...

Ferrocenyl Paclitaxel and Docetaxel Derivatives: Impact of an Organometallic Moiety on the Mode of Action of Taxanes.

A series of ferrocenyl analogues and derivatives of paclitaxel and docetaxel were synthesised and assayed for their antiproliferative/cytotoxic effects, impact on the cell cycle distribution and ability to induce tubulin polymerisation. The replacement of the 3'-N-benzoyl group of paclitaxel with a ferrocenoyl moiety, in particular, led to formation of an analogue that was at least one order of magnitude more potent in terms of antiproliferative activity than the parent compound (IC50 values of 0.11 versus 1.11 μm, respectively), but still preserved the classical taxane mode of action, that is, microtubule stabilisation leading to mitotic arrest. Molecular docking studies revealed an unexpected binding pocket in the tubulin structure for the ferrocenoyl group introduced in the paclitaxel backbone.

Ferrocenyl compounds derived from the reaction of phenylamines with ferrocenecarbonyl chloride: Synthesis, characterisation and their biological activity

Eight ferrocenyl derivatives were synthesized and characterised by NMR, elemental analyses and X-ray single crystal diffraction analysis. The anticancer activities of the eight compounds were assessed where applicable in the two breast cancer cell lines, MCF-7 and MDA-MB-231. It was found that the cytotoxicity of N-Phenyl-N-(2-Methyl-4-Methoxyphenyl)ferrocenecarboxamide (4) and N,N-bis(4-Methoxyphenyl)ferrocenecarboxamide (8) correlates to their relatively positive reduction potentials, which may suggest that the cytotoxicity stems from their involvement in electron transfer process. Furthermore, comparing the activity of N,N-bis(phenyl)ferrocenecarboxamide (3) to that of compounds 4 and 8 suggest that their methoxyl group may undergo demethylation under physiological conditions to generate biologically active species and thus they exhibited better activity in the two breast cancer cell lines compared to compound 3.

ChemInform Abstract: Recent Advances in Iron Complexes as Potential Anticancer Agents

AbstractReview: 199 refs.

Density functional theory investigations on binding and spectral features of complexes of ferrocenyl derivatives with cucurbit [7]uril

Host–guest interactions between ferrocene (Fc) and its derivatives containing electron donating and electron withdrawing substituents viz., 2-ferrocenyl benzoxazole (FcOz) or 2-ferrocenyl benzothiazole (FcTz) and cucurbit [7]uril (CB[7]) host have been analyzed employing density functional theory incorporating various exchange correlation functionals. Electronic structures of these complexes reveal the encapsulation of ferrocene ring within the CB[7] container with the benzoxazole or benzothiazole substituent interacting with host portals via C=O⋯H interactions. Further the M06-2X based calculations show stronger host–guest binding compared to those predicted from wB97x, PBE0 and B3LYP functionals. The contributions of electrostatic and other dispersive interactions toward such binding have been assessed. The 1H NMR chemical shifts from the gauge independent atomic orbital (GIAO) theory using different functionals demonstrated that subtle changes in δH signals of cyclopentadienyl protons and those encapsulated in the CB[7] cavity in water are better reproduced by the wB97x functional. Calculated infrared spectra revealed that the complexation is accompanied by frequency shift of the C–N stretching in benzoxazole or benzothiazole ring, and the characteristic methine and carbonyl vibrations of CB[7]. The direction of such frequency shifts has been explained from the natural bond orbital analyses and ‘Quantum Theory of Atoms in Molecules’ approach. Time dependent density functional theory calculations further demonstrated that substitution on the cyclopentadienyl ring brings a bathochromic shift of the ~200nm band in the electronic spectra for the unsubstituted Fc-CB[7] complex. Furthermore, FcOz@CB[7] or FcTz@CB[7] complexes exhibit low energy absorption band at ~480nm in its electronic spectra as a result of intramolecular charge transfer from 3d orbitals of Fe to π* orbitals of benzothiazole or benzoxazole, unlike that in the Fc@CB[7] complex.

High Efficency Synthesis of Ferrocenyl Derivatives Catalyzed by Trace Amount Cyclopalladated Complex

High Efficency Synthesis of Ferrocenyl Derivatives Catalyzed by Trace Amount Cyclopalladated Complex

Assessment of the nematocidal activity of metallocenyl analogues of monepantel

In this study, we present the design, synthesis, characterization and biological evaluation of structurally new ferrocenyl and ruthenocenyl derivatives of the organic anthelmintic monepantel (Zolvix®). All seven metallocenyl derivatives prepared (4a/b, 5a/b, 6a/b and 7) were isolated as racemates and characterized by 1H, 13C and 19F NMR spectroscopies, mass spectrometry, IR spectroscopy and elemental microanalysis. The molecular structures of four compounds (4a/b, 6a and 7) were further confirmed by X-ray crystallography. The biological activities of the organometallic intermediates (4a/b) and organometallic derivatives of monepantel (5a/b, 6a/b and 7) were evaluated in vitro using parasitic nematodes of major importance in livestock, namely Haemonchus contortus and Trichostrongylus colubriformis. Two ferrocenyl compounds (4a and 6a) showed nematocidal activity, while the analogous ruthenocenyl compounds (4b and 6b) were not active at the highest concentration tested (10 μg mL-1). In order to obtain insight into the difference in activity between ferrocenyl and ruthenocenyl derivatives, the potential of the compounds for reactive oxidative species (ROS) production in live cells was assessed. Interestingly, neither the ferrocenyl nor the ruthenocenyl compounds (4a/b and 6a/b) produced significant ROS in HeLa cells when checked after 22 h, potentially indicating a redox-independent activity of 4a and 6a on the parasites. The selectivity of the compounds on parasites was confirmed by investigating their cytotoxicity profiles. None of these compounds was toxic either to HeLa or MRC-5 cells. Thus, 4a and 6a could be considered as interesting leads for further development of new classes of anti-parasitic agents.

Antiplasmodial activity of iron(II) and ruthenium(II) organometallic complexes against Plasmodium falciparum blood parasites.

This work reports the in vitro activity against Plasmodium falciparumblood forms (W2 clone, chloroquine-resistant) of tamoxifen-based compounds and their ferrocenyl (ferrocifens) and ruthenocenyl (ruthenocifens) derivatives, as well as their cytotoxicity against HepG2 human hepatoma cells. Surprisingly with these series, results indicate that the biological activity of ruthenocifens is better than that of ferrocifens and other tamoxifen-like compounds. The synthesis of a new metal-based compound is also described. It was shown, for the first time, that ruthenocifens are good antiplasmodial prototypes. Further studies will be conducted aiming at a better understanding of their mechanism of action and at obtaining new compounds with better therapeutic profile.

Corrosion inhibition of carbon steel XC70 in H&lt;sub&gt;2&lt;/sub&gt;SO&lt;sub&gt;4&lt;/sub&gt; solution by ferrocene derivative 3-(ferrocenylmethylamine)benzonitrile

In this work, we studied the efficiency of corrosion inhibition of carbon steel XC70 in H 2 SO 4 0.5 M aqueous solution using ferrocenyl derivatives synthesized in our laboratory, this compound is: 3-(ferrocenylmethylamine)benzonitrile. The inhibitory potential of this compound was determined by electrochemical techniques based on Tafel segments. The results show that the studied compound has an efficiency of inhibition which depends on its concentration. The adsorption of these compounds on the surface of the metal is a chemical adsorption. The inhibition of corrosion reached 84 % at a concentration of 50 ppm.

Some ferrocenyl chalcones as useful candidates for cancer treatment.

Although knowledge of cancer management is extensive, mortality is not currently declining in this area. It is therefore important to implement a long-term strategy that would aim to prevent these serious diseases. Ferrocene-related organometallic compounds are promising candidates for design of new drugs since they can exhibit much greater biological activity than their phenyl analogs. In our work, we focused on investigating the cytotoxic and antiproliferative effects of five ferrocenyl derivatives toward selected tumor cell lines. We found that some of these substances significantly reduced Jurkat cell survival and, to a lesser extent, that of the HeLa, MCF7, A549, and MDA cells. Long-term treatment of HeLa cell cultures with these agents resulted in a significant blockade of formation of tumor cell colonies. We found that one of the mechanisms of action of the compounds is likely to display an effect on the redox state of the mitochondria at a final concentration of 10(-4) and 10(-5) mol l(-1). Of the compounds tested, the indanonyl ferrocene derivative (C) was the most effective, especially via glutathione depletion. Based on the obtained results, it can be concluded that synthetic substances containing iron have potential antitumor activity.

One-pot sonochemical synthesis of ferrocenyl derivatives via a three-component reaction in aqueous media

An ultrasound-assisted three-component, one-pot domino reaction with ferrocenecarboxaldehyde is herein reported. The sequence of reactions entails the allylindation and dehydrative alkylation of stabilized C-nucleophiles (e.g. electron-rich – (hetero)aromatics and stabilized enols) and N-nucleophiles (e.g. azoles). Sonochemical reactions have been performed in three different high-intensity reactors: a bath (20.3kHz, 60W), as well as two cup horns working at 19.9kHz (75W) and 300.5kHz (70W) giving a library of 18 new ferrocenyl derivatives.

Toward organometallic antischistosomal drug candidates.

In the recent years, there has been a growing interest in the use of novel approaches for the treatment of parasitic diseases such as schistosomiasis. Among the different approaches used, organometallic compounds were found to offer unique opportunities in the design of antiparasitic drug candidates. A ferrocenyl derivative, namely ferroquine, has even entered clinical trials as a novel antimalarial. In this short review, we report on the studies describing the use of organometallic compounds against schistosomiasis.

Multidecker Sandwich Complexes VnBenn+1 (n = 1, 2, 3) as Stronger Electron Donor Relative to Ferrocene for Designing High-Performance Organometallic Second-Order NLO Chromophores: Evident Layer Effect on the First Hyperpolarizability and Two-Dimensional NLO Character

During the past 3 decades, significant progress has been made in multidecker sandwich complexes. Replacing metallocene in the metallocene-based second-order nonlinear optical chromophores with multidecker sandwich complexes will create a variety of new second-order NLO organometallic complexes. To explore the possibility of improving NLO properties of organometallic complexes by using multidecker sandwich complexes, we theoretically design five second-order NLO moleculars VnBzn+1-(C2H2)3-NO2 (n = 1, 2, 3) with widely investigated VnBzn+1 (n = 1, 2, 3) by changing the layer number n or position of conjugation π–A system in the D−π–A structure. The NLO properties of these five complexes are investigated in detail. By comparison with the β0 of ferrocenyl derivative Fe(η5-C5H5)2-(C2H2)3-NO2, the larger NLO response (β0, 10215–36917 au) is found in VnBzn+1-(C2H2)3-NO2 (n = 1, 2, 3). The dependence of the first hyperpolarizabilities β0 on the layer number n and the position of conjugation π–A system is discussed in the article. The evident layer effect on the first hyperpolarizabilities β0 is shown. And, the enlargement of the first hyperpolarizability β0 by the layer number n can be rationalized by considering the enhancement of parallel-x-MLCT (from more than one metal center to acceptor, −NO2), perpendicular-x-MLCT (from multiple metal centers to multiple C6H6 ligands) transition and two-dimensional NLO character with the two charge transfer axes. By comparison with ferrocene or V1Bz2, the multidecker sandwich complexes VnBzn+1 (n = 2, 3) can be considered as stronger donor group for designing NLO moleculars. We hope, this groundbreaking work may evoke one’s attention to design new, highly efficient second-order NLO molecular materials with excellent building blocks: multidecker sandwich complexes.

Organized Molecular Assemblies based on Ferrocenyl Derivatives

ABSTRACTOrganic films with a thickness of few nanometers are potentially useful components in many practical and commercial applications such as sensors, detectors, displays and electronic circuit components. In this context, the Langmuir-Blodgett (LB) method is one the most promising techniques for preparing these films.In this work, we report the synthesis and characterization of three new amphiphilic organometallic compounds with ferrocene units, which consist of one ferrocenyl aminocarbene with the general formula FcC=Cr(CO)5NH(CH2)15CH3, and two ferrocenyl amides with the general formula FcC=MNH(CH2)15CH3 where M = S or Se. These new derivatives have been synthesized to study the influence of long alkyl side chain and the hydrophilic head on the film organization behavior at the air-water interface.The Langmuir-Blodgett (LB) technique was focused for building ordered nanostructures in molecular assemblies of ferrocenyl derivatives, which are apt to form a stable and transferable monolayer film. The π-A isotherm, hysteresis, Brewster angle microscopy (BAM) and film stability were used to characterize the behavior of a monolayer film at the air-water interface. Z- type LB films were prepared from molecular monolayers which were transferred onto glass substrates. These films were characterized by atomic force microscopy (AFM), UV-Visible spectra and X-ray diffraction (DRX) techniques.

Tuning the nitrogen content and surface properties of nitrogen-doped carbon nanotubes synthesized using a nitrogen-containing ferrocenyl derivative and ethylbenzoate

Aligned nitrogen-doped carbon nanotubes (N-CNTs) containing 6.4–15.7 wt% of nitrogen were synthesized by pyrolysis of 3-ferrocenyl-2-(4-cyanophenyl)acrylonitrile as the catalyst in either acetonitrile or a solution of acetonitrile and ethylbenzoate. For comparison, N-CNTs were synthesized by pyrolysis of 3-ferrocenyl-2-(4-cyanophenyl)acrylonitrile in toluene. The effect of oxygen and the carbon source used during synthesis was investigated. The use of 3-ferrocenyl-2-(4-cyanophenyl)acrylonitrile in acetonitrile as a nitrogen and carbon source selectively yielded mainly N-CNTs, while use of toluene as a carbon source yielded both N-CNTs and carbon spheres. Elemental analysis of the N-CNTs synthesized using both acetonitrile and ethylbenzoate (source of oxygen) indicated that addition of oxygen enhanced the nitrogen content of N-CNTs. This was further supported by results from Raman spectroscopy, X-ray diffraction (XRD), Fourier transform infrared spectroscopy and inverse gas chromatography surface energy analysis. The higher nitrogen-containing N-CNTs were less graphitic and showed a higher base constant (Kb) compared to N-CNTs synthesized without oxygen. Analysis of transmission electron microscopy images showed that the outer diameters of the N-CNTs decreased upon increasing the oxygen composition by mass in the synthesis precursors from 1 to 4 wt% oxygen, the oxygen was derived from ethylbenzoate. In addition, the scanning electron microscopy and XRD revealed that the alignment of N-CNTs increased upon addition of oxygen. Electrical conductivity measurements of N-CNTs showed a negative relationship between the amount of oxygen in the starting materials and the conductivity of N-CNTs.

Ferrocenyl derivatives of pterocarpene and coumestan: Synthesis, structure and anticancer activity studies

Organometallic derivatives of natural products are gaining increasing importance in medicinal chemistry. A new series of ferrocenylated chromones [3-(1-ferrocenylethynyl)chromone 12, 6-fluoro-3-(1-ferrocenylethynyl)chromone 13, and 6-(1-ferrocenylethynyl)chromone 14], ferrocenyl derivatives of pterocarpene [2-ferrocenyl-4H-furo[3,2-c]chromene 9, and 2-ferrocenyl-6-fluoro-4H-furo[3,2-c]chromene 10] and coumestan [2-ferrocenyl-furo[3,2-c]chromen-4-one 11] have been synthesised and fully characterized. Complexes 12–14 have been obtained by the Sonagashira cross-coupling reaction using bromochromone and ethynylferrocene as commercially available precursors respectively. Compounds 9 and 10 have been obtained in Au-catalyzed one-pot cascade addition/cyclization/H-transfer reactions while coumestan derivative 11 has been obtained in a one-pot cascade Pd-coupling/addition/cyclization/oxidation reaction. The molecular structures of the compounds 11, 13 and 14 in the solid state have been determined by single-crystal X-ray analysis. In the crystal packing of 13, an infinite network along the b axis has been observed. The electrochemical behaviour of all newly obtained compounds has been examined by cyclic voltammetry. Compounds 9–14 undergoes one ferrocenyl-centred reversible oxidation which, in the case of derivatives 9–11, is followed by an irreversible oxidation process at higher potentials. The anticancer activity of the obtained complexes has been evaluated against human estrogen receptor-responsive MCF-7, estrogen receptor-unresponsive MDA-MB-231 mammary carcinoma cells and HT-29 colon carcinoma cells. Compounds 12 and 13 have shown the highest activity with the IC50 values between 19 and 43 μM against all cancer cell lines. Complex 10 has shown enhanced genotoxic effect in compare to Fe-free coumestrol.

Ferrocenyl derivative of 1,8-naphthalimide as a new turn-on fluorescent sensor for Au(III) ion

Two new compounds containing a ferrocene unit and a strongly fluorescent naphthalimide moiety were designed and successfully synthesized. The incorporation of a hydrophilic triethylene glycol unit can enhance the water-solubility and facilitate the dispersion of compounds in aqueous media. The presence of the ferrocene unit in both compounds results in molecules with low quantum efficiencies due to the photo-induced electron transfer (PET) from naphthalimide to ferrocene. However, one of these compounds exhibits a selective fluorescent turn-on by the addition of Au(III) ion with low to negligible interference by 100-fold concentration of other metal ions in acetonitrile/water. Under optimum conditions, the detection limit for Au(III) ion was 95 ppb.

Atypical McMurry cross-coupling reactions leading to a new series of potent antiproliferative compounds bearing the key [ferrocenyl-ene-phenol] motif.

In the course of the preparation of a series of ferrocenyl derivatives of diethylstilbestrol (DES), in which one of the 4-hydroxyphenyl moieties was replaced by a ferrocenyl group, the McMurry reaction of chloropropionylferrocene with a number of mono-aryl ketones unexpectedly yielded the hydroxylated ferrocenyl DES derivatives, 5a–c, in poor yields (10%–16%). These compounds showed high activity on the hormone-independent breast cancer cell line MDA-MB-231 with IC50 values ranging from 0.14 to 0.36 µM. Surprisingly, non-hydroxylated ferrocenyl DES, 4, showed only an IC50 value of 1.14 µM, illustrating the importance of the hydroxyethyl function in this promising new series. For comparison, McMurry reactions of the shorter chain analogue chloroacetylferrocene were carried out to see the difference in behaviour with mono-aryl ketones versus a diaryl ketone. The effect of changing the length of the alkyl chain adjacent to the phenolic substituent of the hydroxylated ferrocenyl DES was studied, a mechanistic rationale to account for the unexpected products is proposed, and the antiproliferative activities of all of these compounds on MDA-MB-231 cells lines were measured and compared. X-ray crystal structures of cross-coupled products and of pinacol-pinacolone rearrangements are reported.

Synthesis, Structure, and Spectroelectrochemistry of Ferrocenyl–Meldrum’s Acid Donor–Acceptor Systems

The synthesis of two new donor–acceptor ferrocenyl derivatives with Meldrum’s acid based nonplanar acceptor substituents is presented. Both compounds are obtained in high yields in a simple reaction protocol under mild conditions using either 1-acetyl- or 1,1′-diacetylferrocene and Meldrum’s acid. Both products have been characterized spectroscopically, by single-crystal X-ray structure analysis, by electrochemical and UV/vis/IR spectroelectrochemical measurements, and by (TD)-DFT calculations. The spectroelectrochemical measurements disclose that the 2,2-dimethyl-1,3-dioxane-4,6-dione moiety is a moderately strong electron acceptor.