Ferrocenyl Polymers Research Articles

Site-Directed Electrochemical Grafting for Amplified Detection of Antibody Pharmaceuticals.

Antibody pharmaceuticals have become the most popular immunotherapeutic drugs and are often administered with low serum drug dosages. Hence, the development of a highly sensitive method for the quantitative assay of antibody levels is of great importance to individualized therapy. On the basis of the dual signal amplification by the glycan-initiated site-directed electrochemical grafting of polymer chains (glyGPC), we report herein a novel strategy for the amplified electrochemical detection of antibody pharmaceuticals. The target of interest was affinity captured by a DNA aptamer ligand, and then the glycans of antibody pharmaceuticals were decorated with the alkyl halide initiators (AHIs) via boronate cross-linking, followed by the electrochemical grafting of the ferrocenyl polymer chains from the glycans of antibody pharmaceuticals through the electrochemically controlled atom transfer radical polymerization (eATRP). As the glycans can be decorated with multiple AHIs and the grafted polymer chains are composed of tens to hundreds of electroactive tags, the glyGPC-based strategy permits the dually amplified electrochemical detection of antibody pharmaceuticals. In the presence of trastuzumab (Herceptin) as the target, the glyGPC-based strategy achieved a detection limit of 71.5 pg/mL. Moreover, the developed method is highly selective, and the results of the quantitative assay of trastuzumab levels in human serum are satisfactory. Owing to its uncomplicated operation and cost-effectiveness, the glyGPC-based strategy shows great promise in the amplified electrochemical detection of antibody pharmaceuticals.

Role of dendritic pendant sizes in the self-assembly of redox-responsive ferrocene-containing polymers to large compound micelles

Polymer self-assembly has attracted considerable attention for constructing interesting nanostructures. Dendronized polymers with a linear polymer backbone and dendritic wedges possess the potential to self-assemble into ordered nanostructures in solution. Herein, the self-assembly behaviors of dendronized ferrocenyl polymers are investigated in aqueous solution. After being oxidized with FeCl3·6H2O, dendronized ferrocenyl polymers form positively charged ferrocenium-containing polyelectrolytes to generate nano-objects in aqueous solution. In addition, the supramolecular polymers obtained from the host–guest interactions between ferrocenyl units and β-cyclodextrin are also able to form nano-objects in aqueous solution. Whereafter, both the oxidized and supramolecular polymers are used to encapsulate Rhodamine B, resulting in the cargo-loaded self-assembly. All self-assembly experiments demonstrate that the dendritic effects would drive ferrocenyl polymers to self-assemble from small micelles to large compound micelles. The ferrocenyl polymers with larger dendritic pendant sizes have a more obvious tendency to self-assemble into large compound micelles. The current work gives a chance to understand the self-assembly behaviors of dendronized polymers, which is expected to generate ordered nanostructures.

Folic acid electrocatalytic oxidation on the carbon electrode surface modified with ferrocenyl grafted polymethylhydrosiloxane

In this research, we synthesized ferrocenyl‐grafted polymethylhydrosiloxane (PMHS) through a hydrosilylation reaction between 3‐butenylferrocene and PMHS. The incorporation of the ferrocenyl derivative into the polymer backbone imparted electrochemical properties to the modified polymer. The modification of the polymer was confirmed by various techniques, including FT‐IR, 1H NMR, and UV–Vis spectroscopy. To prepare the new ferrocenyl polymer, we utilized cross‐linking agents, namely terephthaldehyde (TPA) and fresh egg white (FEW). The resulting polymer was drop‐coated onto a glassy carbon electrode (GCE) surface (5 μL). Electrochemical impedance spectroscopy (EIS) analysis confirmed the successful immobilization of the polymer on the GCE surface. Under physiological pH conditions (pH = 7), the Fc/Fc + couple facilitated the oxidation of folic acid (FA) at a potential of 0.40 V vs. the Ag/AgCl reference electrode. The GC/PMHS‐Fc/(TPA + FEW) electrode exhibited excellent stability, retaining 89% and 90% of its electrocatalytic activity after 500 cycles and 30 days of storage in a refrigerator, respectively. Thus, it shows promising potential for the determination of FA in biological fluids. The ferrocene‐modified electroactive polymer demonstrated satisfactory linear ranges for FA determination (5–150 μM) and a low limit of detection (LOD = 36 nM). These results highlight the effectiveness of the new polymer in detecting FA in biological samples.

Facile Synthesis of Microporous Ferrocenyl Polymers Photocatalyst for Degradation of Cationic Dye

Microporous organic polymers (MOPs) were prepared by condensation reactions from substituent-group-free carbazole and pyrrole with 1,1′-ferrocenedicarboxaldehyde without adding any catalysts. The resultant MOPs were insoluble in common solvent and characterized by FTIR, XPS, TGA and SEM. An N2 adsorption test showed that the obtained polymers PFcMOP and CFcMOP exhibited Brunauer–Emmett–Teller (BET) surface areas of 48 and 105 m2 g−1, respectively, and both polymers possessed abundant micropores. The MOPs with a nitrogen and ferrocene unit could be potentially applied in degrading dye with high efficiency.

A universal biosensor utilizing bacteria-initiated in situ growth of electroactive polymers for bacteria-related hazards detection

Here, an ultrasensitive and highly selective electrochemical biosensor is engineered by integrating bacteria-initiated click chemistry with in situ growth of electroactive polymers. Leveraging the unique copper-binding redox pathway of bacteria to reduce CuII to CuI, CuI-catalyzed click chemistry is initiated and high-density electroactive ferrocenyl polymers are subsequently generated and efficiently grafted on biosensing interface by potentiostatic electrochemical atom transfer radical polymerization that greatly enhances the sensitivity of electro-analytical performance. A good linearity between electrochemical signal and the logarithm of Staphylococcus aureus and Escherichia coli concentration over the range from 102 to 107 CFU/mL is obtained with detection limits down to 4 and 6 CFU/mL, respectively. In order to further expand the applicability and universality of the sensor, bacterial magnetic separation section is supplemented into the system. With the help of aptamer-based magnetic preseparation section, selective detection of target bacteria with great anti-interference is achieved in complex real samples. Moreover, this biosensor can be applied in convenient antibiotics residue detection and rapid drug resistance analysis by merely substitution of recognition element or preincubation of bacteria with different anti-bacteria drugs. Thus, after further expansion of bacterial magnetic separation section or simple replacement of the originally identification element, a universal biosensor including bacteria analysis system and antibiotics detection system with excellent analytical performance is constructed. It provides new insight into the aspects of bacteria-related hazards detection that could not only reduce the detriment caused by bacterial contamination, but also guide antibiotic rational usage and help to control the emergence of multidrug-resistant bacteria.

Bioinspired Electro-RAFT Polymerization for Electrochemical Sensing of Nucleic Acids.

Sensing of ultralow-abundance nucleic acids (NAs) is integral to medical diagnostics and pathogen screening. We present herein an electrochemical method for the highly selective and amplified sensing of NAs, using a peptide nucleic acid (PNA) recognition probe and a bioinspired electro-RAFT polymerization (BERP)-based amplification strategy. The presented method is based on the recognition of target NAs by end-tethered PNA probes, the labeling of thiocarbonylthio reversible addition-fragmentation chain transfer (RAFT) agents, and the BERP-assisted growth of ferrocenyl polymers. The dynamic growth of polymers is electrochemically regulated by the reduction of 1-methylnicotinamide (MNA) organic cations, the redox center of nicotinamide adenine dinucleotide (NAD+, coenzyme I). Specifically, electroreduction of the MNA cations causes the fragmentation of thiocarbonylthio RAFT agents into radical species, triggering the polymerization of ferrocenyl monomers, thereby recruiting plenty of ferrocene electroactive tags for amplified sensing. It is obvious that the BERP-based strategy is inexpensive and simple in operation. Benefiting from the high specificity of the PNA recognition probe and the amplified signal by the BERP-based strategy, this method is highly selective and the detection limit is as low as 0.58 fM (S/N = 3). Besides, it is applicable to the sensing of NAs in serum samples, thus showing great promise in the selective and amplified sensing of NAs.

Coenzyme-Mediated Electro-RAFT Polymerization for Amplified Electrochemical Interrogation of Trypsin Activity.

Trypsin is a key proteolytic enzyme in the digestive system and its abnormal levels are indicative of some pancreatic diseases. Taking advantage of the coenzyme-mediated electrografting of ferrocenyl polymers as a novel strategy for signal amplification, herein, a signal-on cleavage-based electrochemical biosensor is reported for the highly selective interrogation of trypsin activity at ultralow levels. The construction of the trypsin biosensor involves (i) the immobilization of peptide substrates (without free carboxyl groups) via the N-terminus, (ii) the tryptic cleavage of peptide substrates, (iii) the site-specific labeling of the reversible addition-fragmentation chain transfer (RAFT) agents, and (iv) the grafting of ferrocenyl polymers through the electro-RAFT (eRAFT) polymerization, which is mediated by potentiostatic reduction of nicotinamide adenine dinucleotide (NAD+) coenzymes. Through the NAD+-mediated eRAFT (NAD+-eRAFT) polymerization of ferrocenylmethyl methacrylate (FcMMA), the presence of a few tryptic cleavage events can eventually result in the recruitment of a considerable amount of ferrocene redox tags. Obviously, the NAD+-eRAFT polymerization is low-cost and easy to operate as a highly efficient strategy for signal amplification. As expected, the as-constructed biosensor is highly selective and sensitive toward the signal-on interrogation of trypsin activity. Under optimal conditions, the detection limit can be as low as 18.2 μU/mL (∼72.8 pg/mL). The results also demonstrate that the as-constructed electrochemical trypsin biosensor is applicable to inhibitor screening and the interrogation of enzyme activity in the presence of complex sample matrices. Moreover, it is low-cost, less susceptible to false-positive results, and relatively easy to fabricate, thus holding great potential in diagnostic and therapeutic applications.

Electrochemically induced grafting of ferrocenyl polymers for ultrasensitive cleavage-based interrogation of matrix metalloproteinase activity

Being closely associated with a variety of physiological and pathological processes, matrix metalloproteinases (MMPs) are useful as potential targets for drug therapy and informative markers for disease diagnosis. On the basis of the electrochemically induced grafting of ferrocenyl polymers and the proteolytic cleavage of recognition peptide, a novel electrochemical sensor is presented in this work for the highly specific interrogation of MMP activities at ultralow levels. The recognition peptide, to be immobilized via the N-terminus, is free of carboxyl group. The presence of the target MMP would cleave the end-tethered recognition peptide, generating a free carboxyl group at the C-terminus of the rest fragment. To be used as the reversible addition−fragmentation chain-transfer (RAFT) agent, the dithiobenzoate, 4-cyano-4-(phenylcarbonothioylthio)pentanoic acid (CPAD), can therefore be tethered via the carboxylate-Zr(IV)-carboxylate chemistry. Subsequently, the grafting of ferrocenyl polymers through electrochemically induced RAFT (eRAFT) polymerization of ferrocenylmethyl methacrylate (FcMMA) would recruit a large quantity of Fc redox reporters on electrode surface. With benefits from the excellent specificity of the enzyme-substrate recognition, the presented cleavage-based sensor is highly selective. Under optimal conditions, the detection limit in the presence of MMP-2 as the model target can be as low as 0.27 pg mL−1, with a linear range from 1 pg mL−1 to 1 ng mL−1. Furthermore, its applicability in the interrogation of MMP activity in complex serum samples and the screening of MMP inhibitors is satisfactory. The presented cleavage-based electrochemical MMP sensor is easy to fabricate and low-cost, thus showing great promise in drug discovery and disease diagnosis.

Electrochemically Controlled ATRP for Cleavage-Based Electrochemical Detection of the Prostate-Specific Antigen at Femtomolar Level Concentrations.

As a single-chain glycoprotein with endopeptidase activity, the prostate-specific antigen (PSA) is valuable as an informative serum marker in diagnosing, staging, and prognosis of prostate cancer. In this report, an electrochemical biosensor based on the target-induced cleavage of a specific peptide substrate (PSA peptide) is designed for the highly selective detection of PSA at the femtomolar level, using electrochemically controlled atom transfer radical polymerization (eATRP) as a method for signal amplification. The PSA peptides, without free carboxyl sites, are attached to the gold surface via the N-terminal cysteine residue. The target-induced cleavage of PSA peptides results in the generation of carboxyl sites, to which the alkyl halide initiator α-bromophenylacetic acid (BPAA) is linked via the Zr(IV) linkers. Subsequently, the potentiostatic eATRP of ferrocenylmethyl methacrylate (FcMMA, as the monomer) leads to the surface-initiated grafting of high-density ferrocenyl polymers. As a result, a large amount of Fc redox tags can be recruited for signal amplification, through which the limit of detection (LOD) for PSA can be down to 3.2 fM. As the recognition element, the PSA peptide is easy to synthesize, chemically and thermally stable, and low-cost. Without the necessity of enzyme or nanoparticle labels, the eATRP-based amplification method is easy to operate and low-cost. Results also show that the cleavage-based electrochemical PSA biosensor is highly selective and applicable to PSA detection in complex biological samples. In view of these merits, the integration of the eATRP-based amplification method into cleavage-based recognition is believed to hold great promise for the electrochemical detection of PSA in clinical applications.

Ultrasensitive peptide-based electrochemical detection of protein kinase activity amplified by RAFT polymerization

Since the oversecretion of protein kinases is indicative of multiple human diseases, the screening of their activities is quite important to clinical diagnosis and targeted therapy. In this work, an ultrasensitive peptide-based electrochemical biosensor was presented for the detection of protein kinase activity by using the reversible addition-fragmentation chain transfer (RAFT) polymerization technique as a signal amplification strategy. First, the substrate peptides were tethered to a gold electrode surface via the thiol terminals. After the phosphorylation of substrate peptides by protein kinases, the carboxyl group-containing dithiobenzoates were labeled to the phosphorylated sites via the robust phosphate-Zr4+-carboxylate linkages. Finally, the RAFT polymerization was initiated using ferrocenylmethyl methacrylates (FcMMAs) and dithiobenzoates as the monomers and the RAFT agents, respectively. The grafting of ferrocenyl polymer chains efficiently recruits a great number of electro-active Fc probes to each phosphorylated site, leading to a drastic amplification of the electrochemical signal. With PKA (protein kinase A) as the target, the detection limit of the peptide-based biosensor can be as low as 1.05 mU mL−1. Moreover, it can selectively differentiate the target from other interferents and is applicable for the screening of potential inhibitors as well as the detection of protein kinase activity in complex cell lysates. Therefore, the peptide-based biosensor shows great promise as a universal tool for protein kinase activity detection and inhibitor screening.

Dendronized triazolyl-containing ferrocenyl polymers as stabilizers of gold nanoparticles for recyclable two-phase reduction of 4-nitrophenol

A series of small-sized (about 2.0 nm) gold nanoparticles (AuNPs) with apparent lattice fringes are synthesized by NaBH4 reduction of HAuCl4 in the presence of stabilizing linear or dendronized 1,2,3-triazolyl-containing ferrocenyl polymers. These AuNPs show high catalytic activity for biphasic 4-nitrophenol (4-NP) reduction to 4-aminophenol (4-AP) by NaBH4. The lower generation G1 dendronized polymers (DPs) is a more efficient stabilizer for AuNP catalytic activity in the reduction of 4-NP than linear G0 polymers or bulky G2 DPs. The G1 DP-stabilized AuNPs are robust and easily recyclable, and the catalyst is recovered and reused at least twenty times with progressive smooth AuNP size increase along with some decrease of catalytic activity.

Novel Electrochemical Immunoassay for Carcinoembryonic Antigen Using Ferrocenyl Polymer Nanospheres

ABSTRACTA new electrochemical immunoassay based on a sandwich format was developed for carcinoembryonic antigen using ferrocenyl polymer nanospheres as the recognition elements. Ferrocenyl nanospheres were synthesized by coordination polymerization and characterized by transmission electron microscopy, energy dispersive X-ray spectrometry, and infrared spectroscopy. Monoclonal carcinoembryonic antibodies were immobilized on a nanogold-modified gold electrode to enhance the sensitivity. Polyclonal carcinoembryonic antibodies were conjugated on ferrocenyl polymer nanospheres. Under the optimal conditions, the electrochemical signal increased with the concentration of the analyte from 0.01 to 50 ng mL−1 with a limit of detection equal to 0.004 ng mL−1. The immunosensor provided acceptable reproducibility with coefficients of variation below 10%.

Hyperbranched Ferrocenyl Polymer Film with High Charge Transport Efficiency

The electrochemical behaviors of hyperbranched poly(ferrocenyl-methylsilane) (HPFMS) and linear oligo(ferrocenyldimethylsilane) (LOFS) films were studied systematically by cyclic voltammetry and chronocoulometry under different polymer coverage and solvents. Both poly(ferrocenylsilanes) show stable cyclic voltammographs in LiClO 4 solutions. Compared with LOFS films, HPFMS films exhibit higher charge transport efficiency because of their hyperbranched structure: peak current ( i p) and apparent diffusion coefficient ( D app) for HPFMS films are larger than those for LOFS films, especially at high polymer coverage (3.8 x 10 (-11) vs 3.9 x 10 (-12) cm2/s for HPFMS and LOFS film at the coverage of 2.1 x 10 (-6) mol Fc/cm2). The conceptual models of electrode processes for HPFMS and LOFS films were proposed to account for higher charge transport efficiency of HPFMS films. It is also found that a solvent with the appropriate solubility parameter and polarity, lower viscosity, and higher dielectric constant is in favor of charge transport through polymer films, which is consistent with the proposed model of electrode process for HPFMS films. These results imply that hyperbranched ferrocenyl polymers have the potential to be excellent chemical sensor materials with convenient synthesis and high sensitivity.

Synthesis and Redox Properties of an Electropolymerizable Amido Ferrocenyl Pyrrole-functionalized Dendrimer

A novel diaminobutane-based poly(propyleneamine) ferrocenyl dendrimer functionalized with electrochemically polymerizable pyrrole substituents, DAB-dend-[{η5-C5H4CONH}Fe{η5-C5H4C(O)NH(CH2)3NC4H4}]4 (1), has been prepared and characterized. A secondary reaction product, the dipyrrole derivative [Fe{η5-C5H4C(O)NH(CH2)3NC4H4}2] (2) has been also isolated and used as a model to facilitate the characterization of 1. The molecular structure of 2 has been determined by single crystal X-ray diffraction studies. Glassy carbon electrodes have been successfully modified by electropolymerization of the pyrrole-functionalized derivatives 1 and 2, in dichloromethane/acetonitrile solutions, resulting in visually detectable electroactive ferrocenyl polymer films persistently attached to the electrode surfaces. Osteryoung square wave voltammetry experiments (OSWV) showed that films of the electropolymerized amidoferrocenylpyrrole functionalized dendrimer 1 (poly-1) senses H2PO 4 − in aqueous solution using Li[B(C6F5)4] as supporting electrolyte.

Synthesis and electrochemical properties of phloroglucin‐based ferrocenyl compounds and their application in anion recognition

AbstractPhloroglucin‐based ferrocenyl compounds, including hyperbranched phloroglucin‐based ferrocenyl polymer and phloroglucin‐based ferrocenyl dendrimer (Generation0), were prepared by a convenient approach. Cyclic voltammograms were used to investigate their electrochemical properties, and we found that the scanning rate and solvent had remarkable effects on electrochemical behavior of the compounds. These compounds showed electrochemical responses to the anions, and a selective recognition for H2PO over other anions was observed. © 2007 Wiley Periodicals, Inc. J Appl Polym Sci, 2008

Ferrocenyl Monomers and Polymers of N-Allyl and N-Acrylatenaphthalimides

A series of N-allyl, N-ethylmethacrylate and N-phenylmethacrylatenaphthalimide monomers have been prepared with –C=CFc, –C≡CFc and –C≡CSiMe3 substituents at the 4-position of the naphthalimide ring. All have been characterised by elemental analysis and spectroscopy; the X-ray structure of N-allyl-4-ethenylferrocenylnapththalimide is also reported. Free-radical polymerisation of these monomers gave homopolymers, random co- and terpolymers with polydispersities ranging from 1.7 to 3.2. Incorporation into a polymer matrix has no effect on the spectroscopic and electrochemical properties of the naphthalimide or ferrocenyl components. The ferrocenyl polymers are electrochromic and when oxidised give naphthalimide\({\rightarrow \hbox{Fc}^{+}}\) charge-transfer bands in the NIR; this electrochromism was examined by OTTLE techniques.

Polymerization of Diphenylacetylenes Having a Ferrocenyl Group and Polymer Properties

Polymerization of two diphenylacetylenes having a ferrocenyl group at para or meta position, 1-[p-ferrocenylphenyl]-2-phenylacetylene (p-FcDPA) and 1-[m-ferrocenylphenyl]-2-phenyl-acetylene (m-FcDPA) and properties of the formed polymers were investigated. Both monomers polymerized with TaCl5-n-Bu4Sn catalyst in good yields to give reddish brown polymers. Poly(p-FcDPA) was insoluble in any solvents. On the other hand, poly(m-FcDPA) was soluble in CHCl3, THF, anisole, o-dichlorobenzene, and so on, and its weight-average molecular weight (M w) was 53×104 and fairly high. A free-standing film of poly(m-FcDPA) could be easily fabricated by solution casting. The onset temperature of weight loss (T 0) of poly(m-FcDPA) in air was ca. 310°C, indicating moderate thermal stability. Poly(m-FcDPA) was electrochemically active, and showed redox cycles based on the ferrocene moiety in cyclic voltammetry.

Cyclic siloxanes and silsesquioxanes as cores and frameworks for the construction of ferrocenyl dendrimers and polymers

Starting from 1,3,5,7-tetramethylcyclotetrasiloxane as core, novel ferrocenyl silicon-containing dendrimers have been constructed up to the third generation, which contains 16 peripheral ferrocene moieties. As precursors of these ferrocenyl dendritic molecules, Si— Cl- and Si— allyl-terminated cyclotetrasiloxane-based dendrimers were also built step by step, by the repetition of hydrosilylation and alkenylation reactions as growing steps. The dendritic structures have been confirmed by 1 H, 13 C and 29 Si NMR, infrared spectroscopy, elemental analysis, mass spectrometry and vapor-pressure osmometry. Solution electrochemical studies showed that all the ferrocenyl redox centers attached to the dendritic surface behave as independent, electronically isolated units, so that the dendrimers exchange all the electrons simultaneously at the same potential. We also describe the application of the first redox-active ferrocenyl polymer containing an octakis(dimethylsiloxy)octasilsesquioxane framework, as a mediator in the electrocatalytic oxidation of ascorbic acid. Copyright # 1999 John Wiley & Sons, Ltd.

Organometallic Ferrocenyl Polymers Displaying Tunable Cooperative Interactions between Transition Metal Centers

Due to a dependency on the element in the spacer and its substituents, the extent of the interactions between the ferrocene units of the polymer backbone of 1 and 2 can be varied. The electrochemical behavior of 3 in which the ferrocene units are separated by C2 bridges shows that the cooperative interactions are much less significant for this polymer.

Gas permeation and selectivity of poly(organophosphazene) membranes

A series of poly(organophosphazenes) with the general structure (NP(R) x (OC 6 H 5 ) 2-x ] n , where x≤2 and R= OC 6 H 4 SiMe 3 , OC 6 H 4 SiMe 2 Ph, OC 6 H 4 SiMePh 2 , OC 6 H 4 Br, and OCH 2 CF 3 , and the ferrocenyl polymer (N 3 P 3 (OCH 2 CF 3 ) 4 (œ2-C 5 H 4 ) 2 Fe] n were synthesized. Films of these polymers were examined with respect to their permeability to O 2 , N 2 , CO 2 , He and CH 4 and selectivity ratios were determined. The effect of cross-linking on both the permeation and selectivity values for films of the silyl-bearing polymers was studied.