Ferrocenyl Group Research Articles

Photo and thermal responsive pseudorotaxane crystals comprising ferrocene-containing ammonium salts and crown ethers

Rotaxanes and pseudorotaxanes have garnered increased attention as mechanically interlocked molecular architectures. These interlocked molecules play fundamental roles in the stimuli-responsive properties of a variety of applications. In contrast to studies of these molecules in solutions, aggregates, and films, there is much less information about their operation in crystals. This review summarizes our recent advances in thermal and photoresponsive crystals of pseudorotaxanes and related complexes comprising ferrocene-containing ammonium salts and dibenzo-crown ethers. A total of 33 complexes and eight axle molecules, which were characterized by single-crystal X-ray crystallography, were compared comprehensively. We discuss the relationships between molecular structures and macroscopic crystal motions (e.g., thermal transitions, photoinduced expansion, and bending) of a diverse range of complexations with various axle and ring molecules, mixed crystals, and azobenzene substituents. Additionally, we compare the rotatability of the ferrocenyl group for various interlocked complexes in crystals and conclude the important factors necessary to achieve stimuli-responsive pseudorotaxane crystals.

Impact of the ferrocenyl group on cytotoxicity and KSP inhibitory activity of ferrocenyl monastrol conjugates.

The incorporation of the ferrocenyl moiety into a bioactive molecule may significantly alter the activity of the resulting conjugate. By applying this strategy, we designed ferrocenyl analogs of monastrol - the first low molecular weight kinesin spindle protein (KSP) inhibitor. The obtained compounds showed low micromolar antiproliferative activity towards a panel of sensitive and ABC-overexpressing cancer cells. Most cytotoxic compounds exhibited also higher KSP modulatory activity and ability for ROS generation compared to monastrol. The increased bioactivity of the studied compounds can be attributed to the presence of the ferrocenyl group.

Bio functional molecular complexes, ferrocenyl hydrazone based binuclear Cu (II) derivatives: Synthesis, spectral, DNA/BSA binding &in-silico analyses

As a first stage intermediate, designing mononuclear complexes of amine-based phenolic derivatives employing Cu (II) acetate as a central metal ion in a 1:2:1 ratio. In a methanolic solution treated with 1,1′-diacetyl ferrocene dihydrazone and Cu (II) perchlorate hexahydrate to generate a new group of ferrocene based macrocyclic binuclear Cu (II) complexes. To characterize the macrocyclic complexes, physico-chemical studies such as FT-IR, UV–vis, and photoluminescence were used. The binuclear Cu(II) complex [Cu2L1] exhibits two quasi-reversible reduction waves in the potential range The binuclear complex [Cu2L1]hastwowaves of virtually reversible reductionin the potential range of E1pc = −1.01 V and E2pc = −1.37 V in the electrochemical investigation. They show a reduction process that involves two one-electron reductions in steps. The ferrocenyl group of the complexes shows one-electron ferrocene/ferrocenium redox activity, although with differing peak potentials. CT-DNA was used to study DNA binding utilizing spectroscopic techniques such as Circular Dichroism, UV–vis, and Fluorescence. The binding constant (Kb) values for the series of complexes range from 1.3x105 to 5.8 × 105 M−1. The metal complexes all interacted with CT-DNA by an intercalative form of binding, according to fluorescence spectrum analyses. BSA protein binding, on the other hand, indicates a quenching manner of interaction with the binuclear complex system, with binding constants of 1.77 × 106, 1.65 × 106, 2 × 106, 4.8 × 106 and 5.12 × 106 M−1. Molecular docking analysis was used to support and augment the experimental biological studies. Intercalation was seen during the docking of 1BNA with a metal complex due to multiple hydrogen bonding interactions. The ferrocene heterocyclic ring and the naphthyl group of complexes interacted with the BSA protein's ARG and TYR systems.

Microenvironment modulation of cuprous cluster enables inert aryl chlorides activation in single-molecule metallaphotoredox amination

Amination of aryl halides is an important tool in organic synthesis and the activation of inert aryl chlorides is particular difficult. We herein report the first study of aromatic microenvironment modulation of cuprous clusters as single-molecule metallaphotocatalysts (SMPs) for direct phneyl chloride activation in CN coupling reactions. Selenoether L1 was designed to afford aromatic microenvironment with ferrocenyl and phenyl groups. The cuprous cluster [Cu2I2(L1)] (C1) was proved to be an effective white light-driven SMP, successfully catalyzing the amination of aryl halides with carbazole. This method showed a diverse substrate scopes of aryl halides with electronical and structural variety, affording the highest yield of 63% for 4-chlorobenzonitrile. X-ray crystallographic, in situ electron paramagnetic resonance (EPR) spectroscopic study and density functional theory (DFT) calculations demonstrated that the aromatic microenvironment in C1 promoted the effective intermolecular electron transfer via π-π interactions between SMPs and aryl halides. Interestingly, the mechanism of the amination was dependent on the substrates applied. A single electron transfer (SET) and formation of Cu2+ intermediate was found when Ph-I/Ph-Br were applied, while an energy transfer (EnT) route with Cu3+-intermediate was identified when Ph-Cl substrates were used.

Reagentless Sensing of Vancomycin Using an Indium Tin Oxide Electrode Grafted with Molecularly Imprinted Polymer including Ferrocenyl Group.

Vancomycin (VCM) is a first-line antimicrobial agent against methicillin-resistant Staphylococcus aureus, a cause of nosocomial infections. Therapeutic drug monitoring is strongly recommended for VCM-based chemotherapy. The authors attempted to develop a simple VCM sensor based on molecularly imprinted polymer (MIP), which can be used with simple operations. Methacrylic acid (MAA), acrylamide, methylenebisacrylamide, and allylamine carboxypropionate-3-ferrocene (ACPF) were copolymerized in the presence of VCM and grafted from the surface of indium-tin oxide (ITO) to obtain MIP-coated electrodes. The MIP-grafted ITO electrode was used for differential pulse voltammetry (DPV) measurements in a buffer solution containing VCM or whole bovine blood. The obtained current depends on the VCM concentration with high linearity. The dynamic range covered the therapeutic range (20–40 μg/mL) of the VCM but was almost insensitive to teicoplanin, which has a similar structure to VCM. The ITO electrodes grafted by the same procedure except for omitting either VCM or APCF were not sensitive to VCM. The sensitivity of the MIP electrodes to VCM in whole blood and buffered saline, but the background current in blood was higher than that in saline. This high background current was also seen in the deproteinized plasma. Thus, the current is probably originated from the oxidation of low molecular weight reducing agents in the blood. The MIP-grafted ITO electrode using ACPF as a functional monomer would be a promising highly selective sensor for real-time monitoring of VCM with proper correction of the background current.

The redox mechanism of ferrocene and its phytochemical and biochemical compounds in anticancer therapy: A mini review

Cancer is one of the most lethal diseases worldwide that endanger human health. The persistent risk of drug-resistant cancer and the low specificity of antitumor drugs are the biggest obstacles in controlling and eliminating cancer, creating a pressing need to design new cytotoxic agents. The development of cisplatin, with its progress in chemotherapy, established the framework for producing and developing metal-based drugs. A systematic drug design approach has been applied to the advancement of non-platinum chemotherapeutic agents, and a considerable number of such complexes have been developed since then. The primary interest in ferrocenyl complexes' anti-malignant activities was ascribed to the unusual activities observed for ferrocenium salts-ferrocenium trichloroacetate and ferrocenium picrate. Their efficiency was attributed to the redox homeostasis interruption in oncogenic cells, leading to cell apoptosis. The extraordinary structural and mechanistic heterogeneity, low toxicity, intrinsic stability towards heat, light, air, economical cost, catalytic and reversible redox properties make ferrocene hybrids ideal candidates for chemotherapeutics. Despite such properties, only ferrocifen has advanced in preclinical cancer trials. This review aims to provide distinct insights into potential anticancer research to establish novel drug candidates by incorporating ferrocenyl groups into biochemical and phytochemical compounds. Furthermore, this review aids in a better understanding of the ferrocenyl complexes' redox mechanism.

Improving the performance of palladium-catalysed telomerization of 1,3-butadiene by metallocene-based phosphine ligand

By replacing one planar phenyl group of PPh3 with bulkier ferrocenyl or ruthenocenyl group, the performance of resulted metallocene-based phosphine ligand in the telomerization of 1,3-butadiene with methanol has been largely elevated compared to the widely used PPh3. High catalytic efficiency with good selectivity has been obtained under the conditions of high butadiene-to-palladium ratio, low catalyst concentration and relatively low temperature. The advantages of ruthenocenyl phosphine ligand on tolerating alkene impurity and stable regioselectivity under different circumstances has been demonstrated. DFT computations have been conducted and elucidate the origin of such drastically improved performance from the simple change on the substituent of phosphine ligand.

Crystal structure and Hirshfeld surface analysis study of (E)-1-(4-chloro-phen-yl)-N-(4-ferrocenylphen-yl)methanimine.

The substituted cyclo-penta-dienyl ring in the title mol-ecule, [Fe(C5H5)(C18H13ClN)], is nearly coplanar with the phenyl-1-(4-chloro-phen-yl)methanimine substituent, with dihedral angles between the planes of the phenyl-ene ring and the Cp and 4-(chloro-phen-yl)methanimine units of 7.87 (19) and 9.23 (10)°, respectively. The unsubstituted cyclo-penta-dienyl ring is rotationally disordered, the occupancy ratio for the two orientations refined to a 0.666 (7)/0.334 (7) ratio. In the crystal, the mol-ecules pack in 'bilayers' parallel to the ab plane with the ferrocenyl groups on the outer faces and the substituents directed towards the regions between them. The ferrocenyl groups are linked by C-H⋯π(ring) inter-actions. A Hirshfeld surface analysis of the crystal structure indicates that the most important contributions for the crystal packing are from H⋯H (46.1%), H⋯C/C⋯ H (35.4%) and H⋯Cl/Cl⋯H (13.8%) inter-actions. Thus C-H⋯π(ring) and van der Waals inter-actions are the dominant inter-actions in the crystal packing.

Self-Assembly of a Triazolylferrocenyl Dendrimer in Water Yields Nontraditional Intrinsic Green Fluorescent Vesosomes for Nanotheranostic Applications.

The promising field of nanomedicine stimulates a continuous search for multifunctional nanotheranostic systems for imaging and drug delivery. Herein, we demonstrate that application of supramolecular chemistry's concepts in dendritic assemblies can enable the formation of advanced dendrimer-based nanotheranostic devices. A dendrimer bearing 81 triazolylferrocenyl terminal groups adopts a more compact shell-like structure in polar solvents with the ferrocenyl peripheral groups backfolding toward the hydrophobic dendrimer interior, while exposing the more polar triazole moieties as the dendritic shell. Akin to lipids, the compact dendritic structure self-assembles into uniform nanovesicles that in turn self-assemble into larger vesosomes in water. The vesosomes emit green nontraditional intrinsic fluorescence (NTIL), which is an emerging property as there are no classical fluorophores in the dendritic macromolecular structure. This work confirms the hypothesis that the NTIL emission is greatly enhanced by rigidification of the supramolecular assemblies containing heteroatomic subluminophores (HASLs) and by the presence of electron rich functional groups on the periphery of dendrimers. This work is the first one detecting NTIL in ferrocenyl-terminated dendrimers. Moreover, the vesosomes are stable in biological medium, are uptaken by cells, and show cytotoxic activity against cancer cells. Accordingly, the self-organization of these dendrimers into tertiary structures promotes the emergence of new properties enabling the same component, in this case, ferrocenyl group, to function as both antitumoral drug and fluorophore.

Self-Assembly of Functionalized Lipophilic Guanosines into Cation-Free Stacked Guanine-Quartets.

The hierarchical self-assembly of various lipophilic guanosines exposing either a phenyl or a ferrocenyl group in the C(8) position was investigated. In a solution, all the derivatives were found to self-assemble primarily into isolated guanine (G)-quartets. In spite of the apparent similar bulkiness of the two substituents, most of the derivatives form disordered structures in the solid state, whereas a specific 8-phenyl derivative self-assembles into an unprecedented, cation-free stacked G-quartet architecture.

Fabrication of bisferrocenyl derivative grafted HTPB with high iron content and its application in dopamine detection

In this work, we employed an efficient strategy to increase the graft percentage of ferrocene in hydroxyl terminated polybutadiene (HTPB) polymer framework. For this purpose, we use 5-chloro-2-pentanone to attach the two alkylferrocene derivatives to each other. In order to incorporate the obtained bis-alkylferrocene derivatives to the polymer backbone, the chlorine atom at the end of the coupling agent alkyl chain was converted to a silane group using the Grignard reaction. Finally, hydrosilylation reaction of as-synthesized silane derivatives and HTPB in the presence of Speier's catalyst (H2PtCl6) resulted in novel bis-ferrocene modified HTPBs with a variety of iron contents. The iron percentage, viscosity, and glass transition temperature of the novel bis-ferrocene modified HTPBs as essential parameters of polymer characterization were investigated. Obtained polymers are electro-active due to the presence of ferrocenyl groups. Additionally, unlike the virgin polymer (HTPB) they show optical properties. The final polymer was immobilized onto the bare glassy carbon electrode (GCE) surface using the cross-linking effect of terephthaldehyde (TFA) and fresh egg white (FEW). Electrochemical impedance spectroscopy (EIS) confirmed the successful immobilization of the polymer. The ability of the fabricated electrode to mediate dopamine (DA) oxidation was evaluated, and the results show the acceptable detection limits as well as linear ranges for the determination of dopamine using GC/BEFcHTPB/(TFA+FEW).

Estimating Effective Steric and Electronic Impacts of a Ferrocenyl Group in Organophosphines.

A series of monodentate ferrocenylphosphines, Fc3P (1a), Fc2PhP (1b), and Fc2ArP (1c; Fc = ferrocenyl, Ar = 3,4-methylenedioxyphenyl), were prepared, and their electronic and steric properties were quantitatively determined. By the IR measurements of their respective Ni(CO)3(phosphine) complexes, the electronic properties of the ferrocenyl group in organophosphines were estimated to be similar to those of primary alkyl groups. The ferrocenyl group is a better electron donor than a methyl group and a poorer donor than an ethyl group. The gold(I) chloride complexes of 1a–c were prepared and their X-ray crystal structures were determined. The %Vbur parameters for 1a–c were calculated using the X-ray structural data, and their ″Tolman cone angles″ were estimated. The steric influence of the ferrocenyl group in organophosphines was clarified to be larger than those of cyclohexyl, tert-butyl, and o-tolyl groups and is comparable to that of a mesityl group.

Electrochemical Regulation of Antibacterial Activity Using Ferrocene-Containing Antibiotics

Electrochemical Regulation of Antibacterial Activity Using Ferrocene-Containing Antibiotics

Synthesis of a diferrocenylvinylidene complex by migration of a ferrocenyl substituent.

An unusual 1,2-ferrocenyl migration has been observed following reactions of [Ru(dppe)Cp][BArF4] with diferrocenylacetylene, extending the scope of group rearrangments beyond methyl (Wagner-Meerwein) and phenyl entities. Ferrocene-containing bis(alkynes) RC[triple bond, length as m-dash]CArC[triple bond, length as m-dash]CR (R = Fc, Ar = 1,4-phenylene; R = Ph, Ar = 1,1'-ferrocenylene) gave bimetallic bis(vinylidene) complexes following two consecutive rearrangements.

Rapid spatially-resolved post-synthetic patterning of metal-organic framework films.

Reactive inkjet printing was used for fast and facile spatially-controlled post-synthetic patterning of metal-organic framework films. Here, we report use of the reactive inkjet printing technique to rapidly produce patterned electroactive MOF films by covalent attachment of redox-responsive ferrocenyl groups to UiO-66-NH2 on FTO glass. This study paves the way for the wide applicability of reactive printing to MOF film modification.

Generation of Bis(ferrocenyl)silylenes from Siliranes

Divalent silicon species, the so-called silylenes, represent attractive organosilicon building blocks. Isolable stable silylenes remain scarce, and in most hitherto reported examples, the silicon center is stabilized by electron-donating substituents (e.g., heteroatoms such as nitrogen), which results in electronic perturbation. In order to avoid such electronic perturbation, we have been interested in the chemistry of reactive silylenes with carbon-based substituents such as ferrocenyl groups. Due to the presence of a divalent silicon center and the redox-active transition metal iron, ferrocenylsilylenes can be expected to exhibit interesting redox behavior. Herein, we report the design and synthesis of a bis(ferrocenyl)silirane as a precursor for a bis(ferrocenyl)silylene, which could potentially be used as a building block for redox-active organosilicon compounds. It was found that the isolated bis(ferrocenyl)siliranes could be a bottleable precursor for the bis(ferrocenyl)silylene under mild conditions.

Microwave assisted synthesis, characterization and biological activities of ferrocenyl chalcones and their QSAR analysis: Part II

A series of ferrocenyl chalcones using acetylferrocene, with ferrocenyl group at the keto carbonyl group, and different aldehydes were synthesized and their bioefficacy evaluation was done against Sclerotium rolfsii, Alternaria solani and Meloidogyne incognita. In continuation of our quest for potent crop protection products, in the present study, a series of 18 substituted ferrocenyl chalcones were synthesized in which ferrocenyl group was attached to the aldehyde moiety, using ferrocenecarboxyaldehyde and different acetophenones by microwave method (MM) and conventional method (CM) [cf: MM 1 to 5 min; CM 12–40 h] and characterized by various techniques viz. IR, LC-HRMS, 1H-NMR and 13C-NMR. In vitro fungicidal activity showed that compound, (2E)-1-(5-Chloro-2-hydroxyphenyl)-3-ferrocenyl-prop-2-en-1-one (34) (ED50 = 21.50 mg L−1) was found to be most active against S. rolfsii and compound, (2E)-1-(4-Bromophenyl)-3-ferrocenyl-prop-2-en-1-one (21) (ED50 = 31.14 mg L−1) showed highest activity against A. solani. As regards nematicidal activity, compound (2E)-1-(3-Bromophenyl)-3-ferrocenyl-prop-2-en-1-one (29) was more potent with LC50 values of 11.95, 8.07 and 4.34 mg L−1 at 24, 48 and 72 h, respectively. QSAR study revealed that MLR for S. rolfsii (r 2 = 0.9834, q 2= 0.8975) and A. solani (r 2 = 0.9807, q 2= 0.8713) and PLS for M. incognita (r 2 = 0.9023, q 2= 0.7818) were the best models.

Photoinduced Mechanical Motions of Pseudorotaxane Crystals Composed of Azobenzene and Ferrocenyl Groups on an Axle and a Crown Ether Ring.

This work describes the design and characterization of photoresponsive dynamic pseudorotaxane crystals composed of azobenzene and ferrocenyl groups in an ammonium cation axle component threaded through dibenzo[24]crown-8 ether rings. Pseudorotaxanes provide flexibility for cis and trans isomerization of azobenzene groups in a crystal state, enabling reversible bending motions under alternating 360 and 445 nm laser irradiation. For such bending motions, strained azobenzene structures were essential; these motifs were obtained by increasing the bulkiness of the substituents on the axle and ring molecules. In addition, the crystals showed photosalient effects, such as jumping motions, under 445 nm laser irradiation. These motions were assisted by the photoabsorption of the ferrocenyl group, which converted 445 nm laser light into heat. The maximum lifting weight accompanied by the photoinduced mechanical motion of a particular crystal was estimated to be 9600 times the crystal weight. These pseudorotaxane crystals exhibit promising features for applications in micro-nanometer-sized miniature mechanical devices.

Enantioselective Limiting Transport into a Fixed Cavity via Supramolecular Interaction for the Chiral Electroanalysis of Amino Acids Regardless of Electroactive Units.

Although an increasing number of researchers are developing electroanalytical protocols for the chiral recognition of amino acids, the electroactive units of the tested isomers still need to provide corresponding electrical signals. In this study, a supramolecular system was developed for the chiral electroanalysis of amino acids regardless of electroactive units. As a model system, an enantiopure electroactive molecule Fc-(S,S)-1 that includes a ferrocenyl group was synthesized and acted as a guest. Moreover, hydrophobic cyclobis-(paraquat-p-phenylene) (CBPQT4+-2) was used as the host. In the presence of π-π stacking and the attraction of π-electrons, CBPQT4+-2 can encapsulate Fc-(S,S)-1 into its cavity. Next, a screen-printed electrode was utilized for electrochemical chiral recognition. The host was fixed on the surface of the working electrode, and the guest was used as the electroactive chiral selector to support electron transfer. Once different configurations of amino acids (threonine, histidine, glutamine, and leucine) were mixed with the guest, regardless of whether they contained electroactive units, differences in the cyclic voltammetry results of the probe enantiomers could be observed, namely, in the peak currents or peak potentials. However, glutamine was an exception because the L-isomer had a stronger binding affinity with Fc-(S,S)-1 + Cu(II), which would limit the transport of the complex into the cavity of CBPQT4+-2, thereby resulting in a low peak current. Thus, an inverse phenomenon was observed with glutamine. In summary, we believe that this work can increase the testing scope for the chiral recognition of different kinds of isomers using electrochemical tools.

Ferrocenyl-substituted tetrahydrothiophenes via formal [3 + 2]-cycloaddition reactions of ferrocenyl thioketones with donor-acceptor cyclopropanes.

Ferrocenyl thioketones reacted with donor–acceptor cyclopropanes in dichloromethane at room temperature in the presence of catalytic amounts of Sc(OTf)3 yielding tetrahydrothiophene derivatives, products of formal [3 + 2]-cycloaddition reactions, in moderate to high yields. In all studied cases, dimethyl 2-arylcyclopropane dicarboxylates reacted with the corresponding aryl ferrocenyl thioketones in a completely diastereoselective manner to form single products in which (C-2)-Ar and (C-5)-ferrocenyl groups were oriented in a cis-fashion. In contrast, the same cyclopropanes underwent reaction with alkyl ferrocenyl thioketones to form nearly equal amounts of both diastereoisomeric tetrahydrothiophenes. A low selectivity was also observed in the reaction of a 2-phthalimide-derived cyclopropane with ferrocenyl phenyl thioketone.