Study on the anti-cancer activity of α-phenethylamine ferrocenecarboxylic acid co-crystals.

Ferrocene derivatives show a wide range of pharmacological activities in the medical field, especially in the anti-tumor field, and can be used as candidate drugs or lead compounds for the treatment of tumors and other diseases. And α-phenethylamine is an important intermediate for the preparation of fine chemical products. (R)-(+)-1-Phenethylamine ferrocenecarboxylic acid/(S)-(-)-1-phenethylamine ferrocenecarboxylic acid were prepared, named compounds 1 and 2, respectively. Single crystal X-ray diffraction showed that compounds 1 and 2 crystallized in the orthorhombic system space group P21 21 21 , and the crystal structures of compounds 1 and 2 exhibited mirror symmetry. The inhibitory effect of two compounds on SW480, MDA-MB-231, and H1299 cells was tested by MTT colorimetry. The IC50 values of the compounds against cancer cells were also calculated. The anti-cancer effect was more pronounced for compounds in the S-configuration. Compound 2 made the wild-type cancer cells undergo apoptosis, thus preventing cancer; it also had the function of helping the cell gene repair defects.

A simple electrochemical immunosensor based on MWCNTs-COOH/Fc-COOH@CoAl-LDH, nanocomposite for sensitive detection of the tumor marker CA724.

A novel label-free electrochemical immunosensor for the ultrasensitive determination of cancer antigen (CA724) was developed using a novel composite of CoAl layered double hydroxides (CoAl-LDH) and carboxyl-functionalized multiwall carbon nanotubes (MWCNTs-COOH) as platform and ferrocenecarboxylic acid (Fc-COOH) as signal label. The MWCNTs-COOH/Fc-COOH@CoAl-LDH composite was prepared by a convenient and simple one-step ultrasonic method, and various characterization techniques consisting of scanning electron microscopy (SEM), transimission electronic microscopy (TEM), TEM-Mapping, fourier transform infrared (FT-IR), X-ray diffraction (XRD) and X-ray photoelectronic energy spectrum (XPS) were applied to study the size and morphological features. Due to its large specific surface area and multilayer structure, the CoAl-LDH can be post-doped to embed a large amount of signal probe to realize the amplification of the internal reference signal Fc. In addition, the higher conductivity of MWCNTs-COOH compensates for the deficiency of CoAl-LDH, which effectively strengthened the electron transfer efficiency of electrochemical signaling substances. The optimal experimental conditions were detected to be 2.5 mmol of Fc-COOH, 4.0 mg/mL of concentration, pH 6.0, incubation time of 40 min, and incubation temperature of 37 ℃. Under optimal conditions, the fabricated sensor exhibits linearity in a wide dynamic range covering the physiological concentration, from 0.001 to 100 U/mL and the limit of detection (LOD) was 0.03962 mU/mL, the calibration equation is stated as △I = 7.76363 log10CCA724 + 40.50351 (R2 = 0.99674). The sensor is successfully detects trace levels of CA724 in human serum with excellent recovery rates ranging from 100.52 %-102.30 %, proving the synergy of MWCNTs-COOH/Fc-COOH@CoAl-LDH as a promising platform for electrochemical sensing for clinical detection of other disease markers.

Reactive oxygen species responsive chitooligosaccharides based nanoplatform for sonodynamic therapy in mammary cancer.

Sonodynamic therapy (SDT) has been extensively studied as a new type of non-invasive treatment for mammary cancer. However, the poor water solubility and defective biocompatibility of sonosensitizers during SDT hinder the sonodynamic efficacy. Herein, a nanoplatform has been developed to achieve high efficient SDT against mammary cancer through the host-guest interaction of ß-cyclodextrin/5-(4-hydroxyphenyl)-10,15,20-triphenylporphyrin (ß-CD-TPP) and ferrocenecarboxylic acid/chitooligosaccharides (FC-COS). Moreover, the glucose oxidase (GOx) was loaded through electrostatic adsorption, which efficiently restricts the energy supply in tumor tissues, thus enhancing the therapeutic efficacy of SDT for tumors. Under optimal conditions, the entire system exhibited favorable water solubility, suitable particle size and viable biocompatibility. This facilitated the integration of the characteristics of starvation therapy and sonodynamic therapy, resulting in efficient inhibition of tumor growth with minimal side effects in vivo. This work may provide new insights into the application of natural oligosaccharides for construct multifunctional nanocarrier systems, which could optimize the design and development of sonodynamic therapy strategies and even combination therapy strategies.

The Development and Evaluation of Reagentless Glucose Biosensors Using Dendritic Gold Nanostructures as a Promising Sensing Platform.

Reagentless electrochemical glucose biosensors were developed and investigated. A graphite rod (GR) electrode modified with electrochemically synthesized dendritic gold nanostructures (DGNs) and redox mediators (Med) such as ferrocenecarboxylic acid (FCA), 1,10-phenathroline-5,6-dione (PD), N,N,N',N'-tetramethylbenzidine (TMB) or tetrathiafulvalene (TTF) in combination with glucose oxidase (GOx) (GR/DGNs/FCA/GOx, GR/DGNs/PD/GOx, GR/DGNs/TMB/GOx, or GR/DGNs/TTF/GOx) were developed and electrochemically investigated. A biosensor based on threefold-layer-by-layer-deposited PD and GOx (GR/DGNs/(PD/GOx)3) was found to be the most suitable for the determination of glucose. To improve the performance of the developed biosensor, the surface of the GR/DGNs/(PD/GOx)3 electrode was modified with polypyrrole (Ppy) for 5 h. A glucose biosensor based on a GR/DGNs/(PD/GOx)3/Ppy(5 h) electrode was characterized using a wide linear dynamic range of up to 39.0 mmol L-1 of glucose, sensitivity of 3.03 µA mM-1 cm-2, limit of detection of 0.683 mmol L-1, and repeatability of 9.03% for a 29.4 mmol L-1 glucose concentration. The Ppy-based glucose biosensor was characterized by a good storage stability (τ1/2 = 9.0 days). Additionally, the performance of the developed biosensor in blood serum was investigated.

A label-free electrochemical immunosensor for CA125 detection based on CMK-3(Au/Fc@MgAl-LDH)n multilayer nanocomposites modification.

A label-free electrochemical immunosensor was constructed for cancer antigen 125 (CA125) detection based on multiple-enlargement means of layer-by-layer (LBL) assembly of ordered mesoporous carbon (CMK-3), gold nanoparticles (Au NPs) and MgAl layered double hydroxides containing ferrocenecarboxylic acid (Fc@MgAl-LDH). A CMK-3(Au/Fc@MgAl-LDH)n multilaminate nanocomposites was designed using technology of LBL self-assembly among negatively charged Au NPs, positively charged CMK-3 and Fc@MgAl-LDH nanosheets. The CMK-3(Au/Fc@MgAl-LDH)n multilaminate nanocomposites was used as carriers to increase the immobilization of antibody and the number of loading Fc, conductors to strengthen conductivity and enhancers to amplify signal of Fc step-by-step. Besides, this special and excellent way of LBL assembly can immensely amplify the signal of immunosensor and more immobilize the biomolecules, and label-free method is a more simple the measuring way and the procedure. The immunosensor displayed a wider linear range of 0.01 U ml-1-1000 U ml-1 and a lower detection limit of 0.004 U ml-1. Therefore, the sensor can stablely and accurately be applied for CA125 detection in clinical cancer diagnosis.

Sensitive detection of prostate-specific antigen based on dual signal amplification of Fc@MgAl-LDH and NH2-MIL-101(Fe).

An electrochemiluminescence sensor was proposed for detection of prostate-specific antigen (PSA) based on dual-amplification strategy of ferrocenecarboxylic acid@MgAl layered double hydroxides (Fc@MgAl-LDH) and NH2-MIL-101(Fe). An (Au NPs/Fc@MgAl-LDH)n multilayer nanofilm was fabricated by a layer-by-layer self-assembly between positively charged Fc@MgAl-LDH nanosheets and negatively charged Au NPs. The multilayer nanofilms acted as nanocarriers for antibody loading and enhancers to catalyze H2O2 decomposition. NH2-MIL-101(Fe) promoted the production of reactive oxygen species due to peroxidase-mimicking activity and increased immobilization of antibodies. This sensor showed a linear detection range of 0.05 pg mL-1 to 50 ng mL-1 with a low detection limit of 0.034 pg mL-1. Moreover, the detection results from this sensor were consistent with data collected from a commercial immunoassay analyzer. The sensor had significant potential for PSA detection in clinical diagnostics.

Cubic Cu2O nanoframes with a unique edge-truncated structure and a good electrocatalytic activity for immunosensor application.

In this work, an ultrasensitive sandwich-type electrochemical immunosensor was developed for the quantitative detection of prostate specific antigen (PSA). Gold nanoparticles decorated 3-aminopropyltriethoxysilane functionalized graphene sheets (Au@APTES-GS) with a large specific surface area, good biocompatibility and superior electron transfer ability were employed as the matrix. In addition, cubic Cu2O nanoframes with hollow edges were employed as the label for the first time. Scanning electron microscope (SEM) images were used to confirm the nanostructure of Au@APTES-GS and Cu2O. Using square wave voltammetry (SWV) to monitor the electrocatalytic process, the signal amplification mechanism of the matrix and the label were explored successfully. Here we find that the unique edge-truncated structure of Cu2O nanoframes can load with a larger amount of redox mediators, ferrocenecarboxylic acid (Fc-COOH), offering a higher electrochemical signal response. Apart from that, Cu2O nanoframes have a good electrocatalytic activity towards the Fc-COOH and hydrogen peroxide (H2O2), making a contribution to further enhance the sensitivity of the fabricated immunosensor. Under optimal conditions, the proposed immunosensor achieved an ultrasensitive and specific detection of PSA, and displayed acceptable reproducibility, selectivity and stability. This work may provide an effective method for the clinical monitoring of tumor markers and demonstrate the potential application promising of nanoframes in the fabrication of immunosensors.

A sandwich-type electrochemical immunosensor for carcinoembryonic antigen based on signal amplification strategy of optimized ferrocene functionalized Fe3O4@SiO2 as labels.

A sandwich-type electrochemical immunosensor was developed for sensitive detection of carcinoembryonic antigen (CEA) by using ferroferric oxide@silica-amino groups (Fe3O4@SiO2-NH2) as carriers and gold nanoparticles-graphene oxide (GO-AuNPs) as platform. The Fe3O4@SiO2-NH2 surface was used as linked reagents for co-immobilization of ferrocenecarboxylic acid (Fc-COOH) and secondary anti-CEA (Ab2) to prepare the signal probe, and it also could hasten the decomposition of hydrogen peroxide (H2O2) to amplify signals. Differential pulse voltammetry (DPV) was successfully used to quantify CEA. Under the optimized conditions, the designed immunosensor shows an excellent analytical performance wide dynamic response range of CEA concentration from 0.001 ng mL(-1) to 80 ng mL(-1) with a relatively low detection limit of 0.0002 ng mL(-1) (S/N=3), and high specificity and good reproducibility. The proposed immunosensor was successfully used to determine CEA in spiked human serum samples.

Monomeric mixed cadmium-2,2'-dipyridylamine complex derived from ferrocenecarboxylic acid: Structural, electrochemical and biological studies.

A mixed Cd(II) complex {[Cd(FcCOO)2(dpyam)(H2O)][Cd(dpyam)2 (H2O)2]·(ClO4)2·CH3OH} (1) (where FcCOO=ferrocenecarboxylic acid and dpyam=2,2'-dipyridylamine), has been synthesized and characterized by FT-IR, (1)H &(13)C NMR, UV-Vis spectroscopy and elemental analysis. The molecular structure of compound 1 has been determined by the single crystal X-ray diffraction technique, which consists of mixed two different cadmium(II) complexes and two uncoordinated perchlorate ions. The crystal packing shows that the compound 1 self-assembled by intermolecular hydrogen bonding via pyridyl N-H⋯O and coordinated water O⋯H-O-H⋯O, to afford the molecule 2D supramolecular network. Compound 1 exhibits high-energy intraligand (π-π(∗)) fluorescence emission. In electrochemical studies of compound 1 shows negative potential compared with ferrocenecarboxylic acid due to formation of coordination complex with Cd ions. The antibacterial study against the distinct bacterial strains show compound 1 has significant activity.

Functionalized gold nanorod-based labels for amplified electrochemical immunoassay of E. coli as indicator bacteria relevant to the quality of dairy product.

In this paper, we report an amplified electrochemical immunoassay for Escherichia coli as indicator bacteria relevant to the quality of dairy product using the functionalized gold nanorod-based labels ({dAb-AuNR-FCA}). The {dAb-AuNR-FCA} labels were designed by exploiting silica-functionalized gold nanorods (AuNR@SiO2) as the carriers for immobilization of detection antibody (dAb) and ferrocenecarboxylic acid (FCA), in which dAb was used for recognition of E. coli and FCA tags served as signal-generating molecule. Greatly amplified signal was achieved in the sandwich-type immunoassay when enormous FCA linked to AuNR@SiO2. Compared with the commercially available {dAb-FCA}, the {dAb-AuNR-FCA} labels exhibited a better performance for E. coli assay due to the advantages of AuNR@SiO2 as carriers. Under optimal experimental conditions, it showed a linear relationship between the peak current of FCA and the logarithmic value of E. coli concentration ranging from 1.0×10(2) to 5.0×10(4) cfu mL(-1) with a detection limit of 60 cfu mL(-1) (S/N=3), and the electrochemical detection of E. coli could be achieved in 3h. Moreover, the proposed strategy was used to determine E. coli in dairy product (pure fresh milk, yogurt in shelf-life, and expired yogurt), and the recoveries of standard additions were in the range of 95.1-106%. This proposed strategy exhibited rapid response, high sensitivity and specificity for E. coli assay in dairy product, and could become a promising technique to estimate the quality of dairy product.

Two novel ferrocenyl dipeptide-like compounds generated via the Ugi four-component reaction.

The Ugi four-component reaction, a powerful method for the synthesis of diverse dipeptide-like derivatives in combinatorial chemistry, was used to synthesize (S)-1'-{N-[1-(anthracen-9-yl)-2-(tert-butylamino)-2-oxoethyl]-N-(4-methoxyphenyl)carbamoyl}ferrocene-1-carboxylic acid dichloromethane disolvate, [Fe(C6H5O2)(C33H31N2O3)]·2CH2Cl2, (I), and (S)-2-(anthracen-9-yl)-N-tert-butyl-2-[N-(4-methylphenyl)ferrocenylformamido]acetamide, [Fe(C5H5)(C33H31N2O2)], (II). They adopt broadly similar molecular conformations, with near-eclipsed cyclopentadienyl rings and near-perpendicular amide planes in their dipeptide-like chains, one of which is almost coplanar with its attached cyclopentadienyl ring but perpendicular to the aromatic ring bound to the N atom. In the supramolecular structure of (I), a two-dimensional network is constructed based on molecular dimers and a combination of intermolecular O-H···O, N-H···O and C-H···O hydrogen bonds, forming R2(2)(11), R2(2)(16), R2(2)(22) and C(9) motifs. These two-dimensional networks are connected by C-H···O and C-H···Cl contacts to create a three-dimensional framework, where one dichloromethane solvent molecule acts as a bridge between two neighbouring networks. In the packing of (II), classical hydrogen bonds are absent and an infinite one-dimensional chain is generated via a combination of C-H···O hydrogen bonds and C-H···π interactions, producing a C(7) motif. This work describes a simple synthesis and the supramolecuar structures of ferrocenyl dipeptide-like compounds and is significant in the development of redox-active receptors.

Multiplexed electrochemical immunoassay of biomarkers using chitosan nanocomposites.

In this work, a novel and sensitive multiplexed immunoassay protocol for simultaneous electrochemical determination of alpha-fetoprotein (AFP) and carcinoembryonic antigen (CEA) was designed using functionalized chitosan composites. The immunosensing platform was prepared via immobilizing capture anti-AFP and anti-CEA on chitosan-Au nanoparticles (AuNPs) through EDC/NHS linking. The signal tags were fabricated by immobilizing electroactive redox probes - Prussian blue (PB) and ferrocenecarboxylic acid (Fc) on chitosan (CHIT), following by absorbing AuNPs to immobilize labeled anti-AFP and anti-CEA, respectively. A sandwich-type immunoassay format was employed for the simultaneous detection of AFP and CEA. The assay was based on the electrochemical oxidation/reduction of the redox species in signal tags, which has a relationship with the concentration of analytes. Experimental results revealed that the multiplexed electrochemical immunoassay enabled the simultaneous monitoring of AFP and CEA with a wide range of 0.05-100 ng mL(-1) for both AFP and CEA. The detection limits (LOD) was 0.03 ng mL(-1) for AFP and 0.02 ng mL(-1) for CEA (S/N=3). The assay results of serum samples with the proposed method were in a good agreement with the reference values from standard ELISA method. And the negligible cross-reactivity between the two analytes makes it possesses potential promise in clinical diagnosis.

Electroactive species-doped poly(3,4-ethylenedioxythiophene) films: enhanced sensitivity for electrochemical simultaneous determination of vitamins B2, B6 and C.

Herein, functionalized PEDOT films were prepared by incorporation of two electroactive species, ferrocenecarboxylic acid (Fc(-)) and ferricyanide (Fe(CN)6(4-)) as doping anions during the electropolymerization of PEDOT at glassy carbon electrodes (GCEs) from aqueous solution. The electrochemically synthesized electroactive species-doped PEDOT films have been carefully characterized by scanning electron microscopy (SEM), FTIR and UV/Vis spectra and various electrochemical techniques. Such nanostructured films combined the advantages of PEDOT (high conductivity and stability) together with electroactive species (good electrochemical activity) and were applied as electrochemical sensors for simultaneous determination of vitamin B2 (VB2), vitamin B6 (VB6) and vitamin C (VC). The results showed that the oxidation peak currents of vitamins obtained at the GCEs modified with electroactive species-doped PEDOT films were much higher than those at the ClO4(-)-doped PEDOT films and bare GCEs. The experiment results also illustrated that the sensors possessed high selectivity with no interference from other potential competing species. Moreover, the proposed sensors were successfully employed for the determination of vitamins in orange juice samples with satisfactory results.

A Molecular-Imprinted Sensor for Trace Detection of Gibberellin Based on Ferrocenecarboxylic Acid Multiply Marked Dendrimer / 分析化学

A novel strategy employing dendrimer to multi-label the template molecule to improve the sensitivity of molecularly imprinted electrochemical sensor was proposed. The determination relies on a competition reaction between poly ( diethylene-triaminepenta-acetic acid )-glycol ester ( PDTPA )-ferrocene-carboxylic acid ( FcA ) labeled gibberellins acid 3 ( GA3 ) and GA3 in the sample. Since one cavity corresponds with multiple FcA, instead of only one FcA, the intensity of the detecting signal was greatly enhanced, so was the sensitivity of the sensor. Experimental results showed that the molecularly imprinted electrochemical sensor was sensitive to GA3 detection at a concentration from 2. 0í10-9 to 1. 0í10-7 mol/L, with a detection limit of 9. 3í10-10 mol/L. In addition, the sensor had good reproducibility and its feasibility was verified in the analysis of series of real beer samples.