Ferrocenyl Group Research Articles

Electrochemical Aptasensor of Human Cellular Prion Based on Multiwalled Carbon Nanotubes Modified with Dendrimers: A Platform for Connecting Redox Markers and Aptamers

The present work aims to develop an electrochemical biosensor based on aptamer able to detect human cellular prions PrP(C) as a model biomarker of prion disease with high sensitivity. We designed the biosensor using multiwalled carbon nanotubes (MWCNTs) modified with polyamidoamine dendrimers of fourth generation (PAMAM G4) which in turn were coupled to DNA aptamers used as bioreceptors. Electrochemical signal was detected by a ferrocenyl redox marker incorporated between the dendrimers and aptamers interlayer. MWCNTs, thanks to their nanostructure organization and electrical properties, allow the distribution of aptamers and redox markers over the electrode surface. We demonstrated that the interaction between aptamers and prion proteins leads to variation in the electrochemical signal of the ferrocenyl group. High sensitivity with a detection limit of 0.5 pM and a wide linear range of detection from 1 pM to 10 μM has been demonstrated. Detection of PrP(C) in spiked blood plasma has been achieved in the same range of concentrations as for detection of PrP(C) in buffer. The sensor demonstrated a recovery of minimum 85% corresponding to 1 nM PrP(C) and a maximum of 127% corresponding to 1 pM PrP(C).

Ferrocenyl Dendrimers with Ionic Tethers and Dendrons

Whereas covalently constructed dendrimers are very numerous, there are only a few examples of dendrimers based on ionic bonds with tethers or dendrons. Here such constructions were designed in order to examine their physicochemical consequences: in particular, the electrochemical and redox properties. Two series of secondary polyamine dendrimers containing ferrocenyl and octamethylferrocenyl were synthesized by condensation of polyamine dendrimers, obtained by reduction of the polyazide dendrimers by LiAlH4 or NaBH4 with ferrocenyl aldehyde or octamethylferrocenyl aldehyde, followed by reduction of the resulting polyimine dendrimers. Primary and secondary ferrocenyl polyammonium dendrimer salts have been synthesized by quaternization of the dendritic amines including ferrocenyl secondary polyamines by reaction with a triferrocenyl dendron containing a carboxylic acid as the focal point. Cyclic voltammetry data show the electrostatic effect of the intradendritic secondary ammonium groups and the distinction between intradendritic and peripheral ferrocenyl groups.

Subporphyrins with an Axial BC Bond

Axial fabrications of subporphyrins have been conveniently accomplished by the reaction of B(methoxo)triphenylsubporphyrin with Grignard reagents such as aryl-, heteroaryl-, ferrocenyl-, β-styryl-, phenylethynyl-, and ethylmagnesium bromides. The axial groups thus introduced are not conjugated with the subporphyrin core. This situation leads to effective fluorescence quenching of subporphyrins when the axial group is strongly electron donating such as 4-dimethylaminophenyl and ferrocenyl groups.

Phosphorus–nitrogen compounds: Part 28. Syntheses, structural characterizations, antimicrobial and cytotoxic activities, and DNA interactions of new phosphazenes bearing vanillinato and pendant ferrocenyl groups

The gradually Cl replacement reactions of spirocyclic mono (1 and 2) and bisferrocenyl cyclotriphosphazenes (3–5) with the potassium salt of 4-hydroxy-3-methoxybenzaldehyde (potassium vanillinate) gave mono (1a–5a), geminal (gem-1b–5b), non-geminal (cis-1b, cis-5b and trans-2b–5b), tri (1c–5c) and tetra-substituted phosphazenes (1d–5d). Some phosphazenes have stereogenic P-center(s). The chirality of 4c was verified using chiral HPLC column. Electrochemical behaviors were influenced only by the number of ferrocene groups, but not the length of the amine chains and the substituent(s). The structures of the new phosphazenes were determined by FTIR, MS, 1H, 13C and 31P NMR, HSQC and HMBC spectral data. The solid-state structures of cis-1b and 4d were examined by single crystal X-ray diffraction techniques. The twelve phosphazene derivatives were screened for antimicrobial activity and the compounds 5a, cis-1b and 2c exhibited the highest antibacterial activity against G(+) and G(−) bacteria. In addition, it was found that overall gem-1b inhibited the growth of Mycobacterium tuberculosis. The compounds 1d, 2d and 4d were tested in HeLa cancer cell lines. Among these compounds, 2d had cytotoxic effect on HeLa cell in the first 48h. Moreover, interactions between compounds 2a, gem-1b, gem-2b, cis-1b, 2c, 3c, 4c, 5c, 1d, 2d and 4d, and pBR322 plasmid DNA were investigated.

Redox-Based Control of the Transformation and Activation of siRNA Complexes in Extracellular Environments Using Ferrocenyl Lipids

We report physical characterization and biological evaluation of complexes of small interfering RNA (siRNA) formed using a cationic lipid [bis(11-ferrocenylundecyl)dimethylammonium bromide (BFDMA)] containing redox-active ferrocenyl groups at the end of each hydrophobic tail. We demonstrate that control over the redox state of BFDMA can be used to influence key physical properties and control the activities of lipoplexes formed using siRNA-based constructs. Specifically, lipoplexes of siRNA and reduced BFDMA lead to high levels of sequence-specific gene silencing in cells, but lipoplexes formed using oxidized BFDMA do not. Lipoplexes of oxidized BFDMA can be activated in situ to induce high levels of silencing by addition of a chemical reducing agent, demonstrating a basis for external control over the activation/delivery of siRNA in cellular environments. Differences in activity arise from the inability of oxidized BFDMA to promote efficient internalization of siRNA; these differences also correlated to significant differences in the nanostructures of these lipoplexes (determined by cryo-TEM) and their ζ potentials as a function of oxidation state. These results are considered in view of recent studies characterizing the nanostructures, properties, and behaviors of lipoplexes formed using BFDMA and macromolecular plasmid DNA. We find that several key structural features and aspects of redox control observed for lipoplexes of plasmid DNA are maintained in complexes formed using smaller and more rigid siRNA. The ability to transform BFDMA in complex media presents opportunities to exert control over the nanostructures and behaviors of siRNA lipoplexes in ways not possible using conventional lipids. The approaches reported here could thus prove useful in both fundamental and applied contexts.

Facile electrochemical biosensor based on a new bifunctional probe for label-free detection of CGG trinucleotide repeat

We have developed a simple and label-free electrochemical assay to detect CGG trinucleotide repeat. For this purpose, a new bifunctional probe (FecNCD2) was developed, in which a recognition part (naphthyridine carbamate dimmer, NCD) was connected with an electro-active part (ferrocenyl group) using a chain of –CO–NH–CH2–CH2–. The results of circular dichroismic measurements indicated that FecNCD2 exhibited a superior performance for selective binding to CGG trinucleotide repeats compared to a previous bifunctional electrochemical probe connected with shorter linker –CH2– (FecNCD1). Then, the electrochemical properties of FecNCD2 were evaluated and were found to show a good redox response due to the ferrocene moiety. Owing to the high performances of FecNCD2, the label-free electrochemical biosensor for CGG repeats was constructed by immobilizing them onto gold disk electrode and by using FecNCD2 as an electrochemical probe in solution. Further CGG repeats in solution were confirmed to be detectable using the CGG modified biosensor in competitive experiments, i.e., by treating it in test solutions containing FecNCD2 and d(CGG)10 or others. No interference of ct-DNA on the CGG detection was also confirmed with this approach. The strategy should have significant potential for the development of versatile and low-cost biosensor for early diagnosis and treatment of neurodegenerative diseases associated with trinucleotide repeats.

Synthesis, Redox Activity of Rigid Ferrocenyl Dendrimers, and Isolation of Robust Ferricinium and Class‐II Mixed‐Valence Dendrimers

The coupling reactions of ethynylferrocene with trihalogenoarenes do not lead to ethynylferrocenyl arenes that are soluble enough to form the basis of a suitable construction of stiff ferrocenylethynyl arene-cored dendrimers, which explains the previous lack of reports on stiff ferrocenyl dendrimers. However, rigid ferrocenyl-terminated dendrimers have been synthesized from 1,3,5-tribromo- and triiodobenzene through Sonogashira and Negishi reactions with 1,2,3,4,5-pentamethyl-1'-ethylnylferrocene (1a), according to 1→2 connectivity. With compound 1a, the construction of a soluble dendrimer (10a) that contained 12 ethynylpentamethylferrocenyl termini was achieved. Stiff dendrimer 10a shows a single, reversible cyclic voltammetry (CV) wave (with adsorption), which disfavors the hopping heterogeneous electron-transfer mechanism that is postulated for redox-terminated dendrimers that contain flexible tethers. The selectivity of these Sonogashira reactions allows the synthesis of an arene-cored dendron (2c) that contains both ethynylferrocenyl and 1,2,3,4,5-pentamethyl-ferrocenylethynyl redox groups, thus leading to the construction of a dendrimer (7c) that contains both types of differently substituted ferrocenyl groups with two well-separated reversible CV waves. Upon selective oxidation, this mixed dendrimer (7c) leads to a class-II mixed-valence dendrimer, 7c[PF6]3, as shown by Mössbauer spectroscopy, whereas oxidation of the related fully pentamethylferrocenylated dendrimer (7a) leads to the all-ferricinium dendrimer, 7a[PF6]6.

Structural influences on the electrochemistry of 1,1′-di(hydroxyalkyl)ferrocenes. Structure of [Fe{η5-C5H4–CH(OH)–(CH2)3OH}2

A series of 1,1′-di(hydroxyalkyl)ferrocenes, [Fc′{(CH2)nOH}2], with n = 1 (1), 2 (2), 3 (3) and 4 (4) and Fc′ = Fe(η5-C5H4)2, was synthesized. The electrochemistry of the di(hydroxyalkyl)ferrocenes was studied by cyclic voltammetry in CH2Cl2/0.1 M [NnBu4][PF6] utilizing a glassy carbon working electrode. The ferrocenyl group showed reversible electrochemistry with the formal reduction potential, Eo′, inversely proportional to alkyl chain length and approximately 59 mV smaller than those of the corresponding mono(hydroxyalkyl)ferrocenes derivatives [Fc(CH2)mOH] with m = 1 (1m), 2 (2m), 3 (3m), and 4 (4m) and Fc = Fe(η5-C5H5)(η5-C5H4−). The tetraalcohol [Fc′{CH(OH)(CH2)3OH}2], 5, possessing four OH functionalities, two in the terminal positions and two more, one on each of the two α-C relative to the ferrocenyl (Fc′ for dialcohols or Fc for monosubstituted derivatives) group, was isolated as a side product during the synthesis of 4. The formal reduction potential of 5 was Eo′=−24mVvs. FcH/FcH+ and closely approached Eo′ of [FcCH(OH)CH3] (Eo′=−11mV), [Fc′{CH(OH)CH3}2] (−21 mV) and 1 (0.00 mV vs. FcH/FcH+). The single crystal X-ray structure of the tetraalcohol 5 (Z = 8, orthorhombic, space group Pbca) was also solved.

Synthesis and (Spectro)electrochemical Behavior of 2,5-Diferrocenyl-1-phenyl-1H-phosphole

2,5-Diferrocenyl-1-phenyl-1H-phosphole (3) has successfully been prepared by a cyclization reaction of phenylphosphine with 1,4-diferrocenyl butadiyne. Subsequent reaction with elemental sulfur and selenium, respectively, leads to the formation of the appropriate phosphole sulfide (4) or selenide (5). Molecules 4 and 5 have structurally been characterized by single-crystal X-ray diffraction. Despite the tetrahedral environment at the phosphorus atom, the cC4P ring itself is planar and coplanar with the cyclopentadienyl rings of the ferrocenyl termini. Electrochemical measurements revealed that the two ferrocenyl groups could be oxidized at discrete potentials, with separation of the individual redox waves of 280 (3), 240 (4), and 235 mV (5), respectively. These values agree with other examples of heterocyclic-bridged diferrocenyl compounds such as diferrocenylthiophene (260 mV) and diferrocenylfuran (290 mV). Compounds [3]+–[5]+ exhibit IVCT absorptions of weak to moderate strength, which conforms well to the predictions of the Hush two-state model for weakly coupled mixed-valence systems. These conclusions are supported by DFT and TD-DFT results, which satisfactorily model the observed structural and spectroscopic parameters. The computational work assists in assigning the various low-energy (LF, IVCT) electronic transitions and also highlights the key role of the unsaturated cis-diene-like C4H2 building block of the heterocycle in promoting the Fc → Fc+ electron-transfer transition.

Synthesis of novel ferrocenyl silyl ethers via dehydrocoupling reactions under Karstedt catalyst

(4-Ferrocenylbutyl)dimethylsilane is prepared by a Grignard reaction from 4-chlorobutylferrocene and chlorodimethylsilane in THF. The Si–H group reacts with primary and secondary alcohols at room temperature to give good yields of (4-ferrocenylbutyl)dimethylsilyl ethers with Karstedt catalyst in THF. Ferrocenyl groups in pendant side chain are attached to cellulose acetate butyrate via alcoholysis at room temperature with Karstedt catalyst.

Heterobimetallic ferrocenylthiosemicarbazone palladium(II) complexes: Synthesis, electrochemistry and antiplasmodial evaluation

Heterobimetallic ferrocenylthiosemicarbazone palladium(II) complexes (3–5) were prepared through the cleavage of a chlorido-bridged palladium ferrocenylthiosemicarbazone intermediate (2) using various P-donor ligands. These compounds were screened for antiplasmodial activity against chloroquine-sensitive (NF54) and chloroquine-resistant (Dd2) Plasmodium falciparum strains, exhibiting biological activity in the low micromolar range. The compounds generally display well-resolved electrochemically reversible one-electron transfer processes for the ferrocenyl group. The half-wave potential for the Fe(II)/Fe(III) couple is electronically influenced by the type of P-donor group through the palladium(II) centre.

On Electrogenerated Acid-Facilitated Electrografting of Aryltriazenes to Create Well-Defined Aryl-Tethered Films

The mechanism of electrogenerated acid-facilitated electrografting (EGAFE) of the aryltriazene, 4-(3,3-dimethyltriaz-1-enyl)benzyl-1-ferrocene carboxylate, was studied in detail using electrochemical quartz crystal microbalance (EQCM) and cyclic voltammetry. The measurements support the previously suggested mechanism that electrochemical oxidation of the EGA agent (i.e., N,N'-diphenylhydrazine) occurs on the forward oxidative sweep to generate protons, which in turn protonate the aryltriazene to form the corresponding aryldiazonium salt close to the electrode surface. On the reverse sweep, the electrochemical reduction of the aryldiazonium salt takes place, resulting in the electrografting of aryl groups. The EGAFE-generated film consists of a densely packed layer of ferrocenyl groups with nearly ideal electrochemical properties. The uncharged grafted film contains no solvent and electrolyte, but counterions and solvent can easily enter and be accommodated in the film upon charging. It is shown that all ferrocene moieties present in the multilayered film are electrochemically active, suggesting that the carbon skeleton possesses a sufficiently high flexibility to allow the occurrence of fast electron transfers between the randomly located redox stations. In comparison, EQCM measurements on aryldiazonium-grafted films reveal that they have a substantially smaller electrolyte uptake during charging and that they contain only 50% electroactive ferrocenyl groups relative to weight. Hence, half of these films consist of entrapped supporting electrolyte/solvent and/or simply electrochemically inactive material due to solvent inaccessibility.

Cathodic Grafting of Alkyl Chains onto Glassy Carbon Easy Immobilization of Ferrocene Used as Redox Probe

ω-Iodo- and α,ω-dihaloalkanes, in contact with glassy carbon (GC) at potentials more negative than -1.7 V vs. Ag/AgCl, can be immobilized at the electrode surface. The process, involving cathodic charge of the graphitized zones of GC and formation of nucleophilic sites within the superficial layersl, is typically carried out in an aprotic organic solvent containing tetraalkylammonium salts. With α,ω-dihaloalkanes, the process is completed by a nucleophilic displacement towards pending C-I functions left after the grafting of the first C-I group. The reaction of negatively charged carbon with bis-(ω-iodoalkyl)ferrocenes was successfully used for immobilization of ferrocenyl groups, an efficient redox probe. The levels of surface coverage were shown to be high, with the apparent surface concentrations of ferrocene greater than 10-8 mol cm-2. The alkylferrocene layers deposited onto carbon are chemically and electrochemically stable; these new superficial structures are expected to be suitable for the use in efficient electricity storage devices.

Heptametallic, Octupolar Nonlinear Optical Chromophores with Six Ferrocenyl Substituents

New complexes with six ferrocenyl (Fc) groups connected to Zn(II) or Cd(II) tris(2,2'-bipyridyl) cores are described. A thorough characterisation of their BPh4(-) salts includes two single-crystal X-ray structures, highly unusual for such species with multiple, extended substituents. Intense, visible d(Fe(II))→π* metal-to-ligand charge-transfer (MLCT) bands accompany the π→π* intraligand charge-transfer absorptions in the near UV region. Each complex shows a single, fully reversible Fe(III/II) wave when probed electrochemically. Molecular quadratic nonlinear optical (NLO) responses are determined by using hyper-Rayleigh scattering and Stark spectroscopy. The latter gives static first hyperpolarisabilities β0 reaching as high as approximately 10(-27) esu and generally increasing with π-conjugation extension. Z-scan cubic NLO measurements reveal high two-photon absorption cross-sections σ2 of up to 5400 GM in one case. DFT calculations reproduce the π-conjugation dependence of β0, and TD-DFT predicts three transitions close in energy contributing to the MLCT bands. The lowest energy transition has octupolar character, whereas the other two are degenerate and dipolar in nature.

Suprarmolecular hydrogels driven by the dual host–guest interactions between α-cyclodextrin and ferrocene-modified poly(ethylene glycol) with low-molecular-weight

In general, α-cyclodextrin (α-CD) and low-molecular weight poly(ethylene glycol) (low-MW PEG) (Mw=400–10,000) cannot construct supramolecular hydrogels but easily form crystalline precipitates. In this study, low-MW PEG (Mn=2000, PEG-2000) was functionalized by ferrocene as mono-end-group. The obtained ferrocene-modified PEG-2000 (FcPEG-2000) further self-assembled into supramolecular hydrogel with α-CD even at low concentration (CFcPEG-2000=17mg/ml), driven by dual host–guest interaction between α-CD and FcPEG-2000. Interestingly, the hydrogel was still observed even when hydrophobic Fc group was oxidized to hydrophilic ferrocenium (Fc+) or included into the cavity of β-CD. In the former case, the existence of Fc+ end groups is considered to decrease the probability of PEG de-penetration from α-CD cavity, so that α-CDs have more location and opportunities to aggregate into more channel-type crystalline domains as physical cross-linking points. While in the later case, the synergistic effect of host–guest interaction between β-CD and ferrocenyl groups and host–guest interaction between α-CD and PEG chains are considered to be the main reason. The resultant FcPEG-2000 based hydrogels showed the property of shear-thinning.

Efficient Electronic Communication in 4,9-Bis(ferrocenylethynyl)dimethyldihydropyrene

Abstract We have prepared the dimethyldihydropyrene (DHP) derivative 2, which possesses two ferrocenyl groups at the 4- and 9-positions through ethynylene linkers. 2 shows intense electronic communication between the two ferrocenyl groups, which is promoted by the highly developed π orbital of the diethynyl DHP moiety.

Ideal Redox Behavior of the High-Density Self-Assembled Monolayer of a Molecular Tripod on a Au(111) Surface with a Terminal Ferrocene Group

A dyad consisting of a tripod-shaped trithiol with an adamantane core and a terminal ferrocenyl group linked through ap-phenyleneethynylene bridge was synthesized. The trithiol formed a stable self-assembled monolayer (SAM) on Au(111), wherein each molecule is bound to the surface by three-point adsorption using all sulfur atoms, with confirmation by PM-IRRAS and XPS analyses. Cyclic voltammetry of the SAM showed a line shape typical of an ideal adsorbed system, that is, a monolayer with negligible electrostatic interaction among the terminal ferrocenyl groups. Thus, a rare SAM was achieved, in which the component molecules were isolated from adjacent molecules without the coadsorption of nonelectroactive molecules.

Synthesis, characterisation, electronic spectra and electrochemical investigation of ferrocenyl-terminated dendrimers

Two new dodecaferrocenyl dendrimers have been prepared using a sixfold Sonogashira coupling reaction and sixfold Huisgen cycloaddition, respectively. In addition, a dendron containing four ferrocenyl groups has been synthesised by conventional synthetic methods. Electrochemical studies have shown that all the ferrocene units are electrochemically equivalent. Moreover, when treated with acid these compounds form multicharged methylium near-infrared-absorbing dendritic dyes with a high extinction coefficient.

Intramolecular electronic communication in ferrocene-based β-diketonato copper(II) complexes as observed by an electrochemical study

The reaction of [Cu(OAc)2.H2O]2 (1) with β-diketones FcCOCH2COR (R=CF3, 2a, CH3, 2b, Ph=C6H5, 2c, and Fc=Fe(η5–C5H4)(η5–C5H5), 2d), afforded in a straightforward synthetic methodology a series of ferrocenyl-functionalized β-diketonato copper(II) complexes 3a–3d of general formula [Cu(FcCOCHCOR)2]. The environment around copper(II) is square planar with the ferrocenyl moieties being positioned opposite to each other. All complexes display in their cyclic voltammograms resolved and electrochemical reversible ferrocenyl oxidations in the range 98⩽Eo′⩽420mV versus FcH/FcH+. An electrochemical and chemical irreversible Cu(II) reduction was observed in the range −1624⩽Epc⩽−1102mV. Good intramolecular communication between neutral ferrocenyl and oxidised, positively charged ferrocenium cations explained the well resolved ferrocenyl redox processes. The observed intramolecular communication was quantified with the linear equation Eo′=98.5ΣχR−629 which relates formal ferrocenyl oxidation potentials with the sum of R-group electronegativities, ΣχR. It was possible to show that in [Cu(FcCOCHCOFc)2], 3d, one ferrocenyl group on each β-diketonato ligand is first oxidized before the second ferrocenyl group on the same β-diketonato ligand is oxidized. In a spectro-electrochemical study, an intervalent charge transfer band (IVCT) could be detected for the mixed valent intermediates of 3d that are electrochemically generated. For complex 3a, only the normal ligand to metal charge transfer band at ca. 650nm was observed. This demonstrate that communication between Fc and Fc+ groups are more effective within a specific β-diketonato ligand, such as (Fc+COCHCOFc) in 3d, than across a copper centre, [Fc+COCHCOR)Cu(FcCOCHCOR)], presumably because of the longer distance between the Fc⋯Fc+ species across the copper centre than within a single ligand.

Charge Transfer Properties of Multi(ferrocenyl)trindenes

Ferrocenyl, diferrocenyl, and triferrocenyl complexes of dihydro-1H-trindene have been prepared by up to 3-fold bromide substitution of the dihydro-2,5,8-tribromo-1H-trindene halocarbon. The charge transfer properties of their mono-, di-, and tricationic derivatives were investigated. The cations of this new family of multi(ferrocenyl)trindene complexes were generated by chemical oxidation using (acetylferrocenium)(BF4) as the oxidative agent and monitored in the visible, IR and near-IR regions. The charge transfer bands in the near-IR spectra are rationalized in the framework of the Marcus–Hush theory. In particular, the triferrocenyl complexes display a redox chemistry that can be switched from a unresolved three-electron oxidation to two consecutive one-electron and two near simultaneously occurring one-electron oxidations by changing the supporting electrolyte from [nBu4N][PF6] to [nBu4][B(C6F5)4]. In addition, the introduction of the third ferrocenyl group increases the strength of the metal–metal interaction with respect to that of the structurally related diferrocenyl system.