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1.
Int J Mol Sci ; 25(9)2024 Apr 28.
Article in English | MEDLINE | ID: mdl-38732028

ABSTRACT

The development of turn-based inhibitors of protein-protein interactions has attracted considerable attention in medicinal chemistry. Our group has synthesized a series of peptides derived from an amino-functionalized ferrocene to investigate their potential to mimic protein turn structures. Detailed DFT and spectroscopic studies (IR, NMR, CD) have shown that, for peptides, the backbone chirality and bulkiness of the amino acid side chains determine the hydrogen-bond pattern, allowing tuning of the size of the preferred hydrogen-bonded ring in turn-folded structures. However, their biological potential is more dependent on their lipophilicity. In addition, our pioneering work on the chiroptical properties of aminoferrocene-containing peptides enables the correlation of their geometry with the sign of the CD signal in the absorption region of the ferrocene chromophore. These studies have opened up the possibility of using aminoferrocene and its derivatives as chirooptical probes for the determination of various chirality elements, such as the central chirality of amino acids and the helicity of peptide sequences.


Subject(s)
Amino Acids , Ferrous Compounds , Metallocenes , Peptides , Ferrous Compounds/chemistry , Amino Acids/chemistry , Metallocenes/chemistry , Peptides/chemistry , Hydrogen Bonding , Stereoisomerism
2.
Langmuir ; 40(23): 12226-12238, 2024 Jun 11.
Article in English | MEDLINE | ID: mdl-38814099

ABSTRACT

We have red-shifted the light absorbance property of a Re(I)-tricarbonyl complex via distant conjugation of a ferrocene moiety and developed a novel complex ReFctp, [Re(Fctp)(CO)3Cl], where Fctp = 4'-ferrocenyl-2,2':6',2″-terpyridine. ReFctp showed green to red light absorption ability and blue emission, indicating its potential for photodynamic therapy (PDT) application. The conjugation of ferrocene introduced ferrocene-based transitions, which lie at a higher wavelength within the PDT therapeutic window. The time-dependent density functional theory and excited state calculations revealed an efficient intersystem crossing for ReFctp, which is helpful for PDT. ReFctp elicited both PDT type I and type II pathways for reactive oxygen species (ROS) generation and facilitated NADH (1,4-dihydro-nicotinamide adenine dinucleotide) oxidation upon exposure to visible light. Importantly, ReFctp showed effective penetration through the layers of clinically relevant 3D multicellular tumor spheroids and localized primarily in mitochondria (Pearson's correlation coefficient, PCC = 0.65) of A549 cancer cells. ReFctp produced more than 20 times higher phototoxicity (IC50 ∼1.5 µM) by inducing ROS generation and altering mitochondrial membrane potential in A549 cancer cells than the nonferrocene analogue Retp, [Re(CO)3(tp)Cl], where tp = 2,2':6',2″-terpyridine. ReFctp induced apoptotic mode of cell death with a notable photocytotoxicity index (PI, PI = IC50dark/IC50light) and selectivity index (SI, SI = normal cell's IC50dark/cancer cell's IC50light) in the range of 25-33.


Subject(s)
Antineoplastic Agents , Ferrous Compounds , Light , Metallocenes , Ferrous Compounds/chemistry , Ferrous Compounds/pharmacology , Humans , Metallocenes/chemistry , Metallocenes/pharmacology , Antineoplastic Agents/chemistry , Antineoplastic Agents/pharmacology , Antineoplastic Agents/radiation effects , Antineoplastic Agents/chemical synthesis , Reactive Oxygen Species/metabolism , Density Functional Theory , Photochemotherapy , Photosensitizing Agents/chemistry , Photosensitizing Agents/pharmacology , Photosensitizing Agents/radiation effects , Photosensitizing Agents/chemical synthesis , Coordination Complexes/chemistry , Coordination Complexes/pharmacology , Coordination Complexes/radiation effects , Coordination Complexes/chemical synthesis , Cell Line, Tumor , Drug Screening Assays, Antitumor , Red Light
3.
J Inorg Biochem ; 257: 112586, 2024 Aug.
Article in English | MEDLINE | ID: mdl-38728860

ABSTRACT

Ferrocene, ruthenium(II) and iridium(III) organometallic complexes, potential substitutes for platinum-based drugs, have shown good application prospects in the field of cancer therapy. Therefore, in this paper, six ferrocene-modified half-sandwich ruthenium(II) and iridium(III) propionylhydrazone complexes were prepared, and the anticancer potential was evaluated and compared with cisplatin. These complexes showed potential in-vitro anti-proliferative activity against A549 cancer cells, especially for Ir-based complexes, and showing favorable synergistic anticancer effect. Meanwhile, these complexes showed little cytotoxicity and effective anti-migration activity. Ir3, the most active complex (ferrocene-appended iridium(III) complex), could accumulate in the intracellular mitochondria, disturb the cell cycle (S-phase), induce the accumulation of reactive oxygen species, and eventually cause the apoptosis of A549 cells. Then, the design of these complexes provides a good structural basis for the multi-active non­platinum organometallic anticancer complexes.


Subject(s)
Antineoplastic Agents , Apoptosis , Coordination Complexes , Ferrous Compounds , Hydrazones , Iridium , Metallocenes , Ruthenium , Humans , Ferrous Compounds/chemistry , Ferrous Compounds/pharmacology , Iridium/chemistry , Iridium/pharmacology , Antineoplastic Agents/pharmacology , Antineoplastic Agents/chemistry , Antineoplastic Agents/chemical synthesis , Metallocenes/chemistry , Metallocenes/pharmacology , Ruthenium/chemistry , Coordination Complexes/pharmacology , Coordination Complexes/chemistry , Coordination Complexes/chemical synthesis , Hydrazones/chemistry , Hydrazones/pharmacology , Hydrazones/chemical synthesis , A549 Cells , Apoptosis/drug effects , Reactive Oxygen Species/metabolism , Cell Proliferation/drug effects
4.
J Inorg Biochem ; 257: 112615, 2024 Aug.
Article in English | MEDLINE | ID: mdl-38772187

ABSTRACT

A series of bis-naphthyl ferrocene derivatives were synthesized and characterized. Based on the results obtained from UV-visible absorption titration and ethidium bromide (EB) displacement experiments, it was observed that the synthesized compounds exhibited a strong binding ability to dsDNA. In comparison to the viscosity curve of EB, the tested compounds demonstrated a bisintercalation binding mode when interacting with CT-DNA. Differential pulse voltammetry (DPV) was employed to assess the binding specificity of these indicators towards ssDNA and dsDNA. All tested indicators displayed more pronounced signal differences before and after hybridization between probe nucleic acids and target nucleic acids compared to Methylene Blue (MB). Among the evaluated compounds, compound 3j containing an ether chain showed superior performance as an indicator, making it suitable for constructing DNA-based biosensors. Under optimized conditions including probe ssDNA concentration and indicator concentration, this biosensor exhibited good sensitivity, reproducibility, stability, and selectivity. The limit of detection was calculated as 4.53 × 10-11 mol/L. Furthermore, when utilizing 3j as the indicator in serum samples, the biosensor achieved satisfactory recovery rates for detecting the BRCA1 gene.


Subject(s)
Biosensing Techniques , DNA , Ferrous Compounds , Metallocenes , Ferrous Compounds/chemistry , Biosensing Techniques/methods , Metallocenes/chemistry , DNA/chemistry , Electrochemical Techniques/methods , Humans , DNA, Single-Stranded/chemistry
5.
Biomacromolecules ; 25(6): 3685-3702, 2024 Jun 10.
Article in English | MEDLINE | ID: mdl-38779908

ABSTRACT

Combination therapy has emerged as a promising approach for treating tumors, although there is room for improvement. This study introduced a novel strategy that combined the enhancement of apoptosis, ferroptosis, and DNA damage to improve therapeutic outcomes for prostate cancer. Specifically, we have developed a supramolecular oxidative stress nanoamplifier, which was comprised of ß-cyclodextrin, paclitaxel, and ferrocene-poly(ethylene glycol). Paclitaxel within the system disrupted microtubule dynamics, inducing G2/M phase arrest and apoptosis. Concurrently, ferrocene utilized hydrogen peroxide to generate toxic hydroxyl radicals in cells through the Fenton reaction, triggering a cascade of reactive oxygen species expansion, reduction of glutathione levels, lipid peroxidation, and ferroptosis. The increased number of hydroxyl radicals and the inhibitory effect of THZ531 on DNA repair mechanisms exacerbated DNA damage within tumor cells. As expected, the supramolecular nanoparticles demonstrated excellent drug delivery ability to tumor cells or tissues, exhibited favorable biological safety in vivo, and enhanced the killing effect on prostate cancer.


Subject(s)
Oxidative Stress , Paclitaxel , Prostatic Neoplasms , Paclitaxel/pharmacology , Paclitaxel/chemistry , Humans , Male , Oxidative Stress/drug effects , Animals , Prostatic Neoplasms/drug therapy , Prostatic Neoplasms/metabolism , Prostatic Neoplasms/pathology , Mice , Metallocenes/chemistry , Nanoparticles/chemistry , Apoptosis/drug effects , Ferrous Compounds/chemistry , Ferrous Compounds/pharmacology , Cell Line, Tumor , beta-Cyclodextrins/chemistry , Polyethylene Glycols/chemistry , Mice, Nude , Ferroptosis/drug effects , Reactive Oxygen Species/metabolism , DNA Damage/drug effects
6.
Int J Biol Macromol ; 269(Pt 2): 132207, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38723823

ABSTRACT

To overcome the low efficacy of sonodynamic therapy (SDT) caused by hypoxia in the tumor microenvironment, we developed a multiple anti-tumor nanoplatform with synergistic SDT, photothermal therapy (PTT), and ferroptosis effects. PCN-224@FcCaO2/Mn/dihydroartemisinin/imiquimod/PDA (PFC) was prepared by modified with dihydroartemisinin (DHA), imiquimod (R837), CaO2, ferrocene (Fc) and Mn2+ on the PCN-224 (Cu) to achieve self-replenishment of H2O2/O2 and GSH consumption. FcCaO2 decomposed into H2O2 in the tumor microenvironment, triggering the Fenton effect to produce OH, and Cu2+ reduced the potential loss of OH by the depletion of GSH. Under ultrasonic (US) and laser irradiation, PFC exhibits exciting PTT and SDT effects from polydopamine (PDA) and PCN-224. Mn2+ not only promoted the reaction of H2O2 to produce O2 to effectively enhance SDT but also induced tumor cell apoptosis by Mn2+ combined with DHA. PFC induced ferroptosis via Fe interaction with DHA to produce ROS and reduce the expression of GPX4. The released R837 and tumor-associated antigens from SDT/PTT can produce damage associated molecular patterns (DAMPs), which can initiate adaptive immune responses to kill cancer cells, and released again to promote the tumor immune cycle. What's more, SDT/PTT and ferroptosis combined with aPD-L1 can effectively suppress both primary and distant tumor growth.


Subject(s)
Indoles , Metal-Organic Frameworks , Photothermal Therapy , Polymers , Indoles/chemistry , Indoles/pharmacology , Polymers/chemistry , Polymers/pharmacology , Humans , Animals , Mice , Photothermal Therapy/methods , Metal-Organic Frameworks/chemistry , Metal-Organic Frameworks/pharmacology , Cell Line, Tumor , Nanoparticles/chemistry , Apoptosis/drug effects , Ferroptosis/drug effects , Tumor Microenvironment/drug effects , Combined Modality Therapy , Immune Checkpoint Inhibitors/pharmacology , Immune Checkpoint Inhibitors/chemistry , Hydrogen Peroxide/pharmacology , Imiquimod/pharmacology , Metallocenes/chemistry , Metallocenes/pharmacology
7.
Molecules ; 29(9)2024 May 05.
Article in English | MEDLINE | ID: mdl-38731638

ABSTRACT

Copper-catalyzed azide-alkyne cycloaddition click (CuAAC) reaction is widely used to synthesize drug candidates and other biomolecule classes. Homogeneous catalysts, which consist of copper coordinated to a ligand framework, have been optimized for high yield and specificity of the CuAAC reaction, but CuAAC reaction with these catalysts requires the addition of a reducing agent and basic conditions, which can complicate some of the desired syntheses. Additionally, removing copper from the synthesized CuAAC-containing biomolecule is necessary for biological applications but inconvenient and requires additional purification steps. We describe here the design and synthesis of a PNN-type pincer ligand complex with copper (I) that stabilizes the copper (I) and, therefore, can act as a CuAAC catalyst without a reducing agent and base under physiologically relevant conditions. This complex was immobilized on two types of resin, and one of the immobilized catalyst forms worked well under aqueous physiological conditions. Minimal copper leaching was observed from the immobilized catalyst, which allowed its use in multiple reaction cycles without the addition of any reducing agent or base and without recharging with copper ion. The mechanism of the catalytic cycle was rationalized by density functional theory (DFT). This catalyst's utility was demonstrated by synthesizing coumarin derivatives of small molecules such as ferrocene and sugar.


Subject(s)
Alkynes , Azides , Click Chemistry , Copper , Cycloaddition Reaction , Copper/chemistry , Click Chemistry/methods , Ligands , Catalysis , Azides/chemistry , Alkynes/chemistry , Coumarins/chemistry , Ferrous Compounds/chemistry , Metallocenes/chemistry , Molecular Structure
8.
Int J Biol Macromol ; 268(Pt 1): 131582, 2024 May.
Article in English | MEDLINE | ID: mdl-38631589

ABSTRACT

Matrix metalloproteinase 9 (MMP-9) plays an important role in wound healing. However, overexpression of MMP-9 leads to the degradation of the newly formed extracellular matrix, which delays wound healing, ultimately leading to chronic wounds. Therefore, timely monitoring of the MMP-9 activity using simple, cost-effective methods is important to prevent the formation of chronic wounds. In this work, ferrocene-modified MMP-9 cleavage peptide (Fc-MG) modified carboxymethyl chitosan hydrogels were prepared as electrochemical biosensors. In the presence of MMP-9, the peptide chain is sheared, and the electrochemically active ferrocene segment is released. Therefore, analyzing the electrochemical activity of hydrogels using differential pulse voltammetry (DPV) can be used to determine MMP-9 activity. The results showed that the DPV peaks were correlated with the MMP-9 concentration in phosphate-buffered saline (PBS, pH 7.4) and Dulbecco's modified Eagle's medium (DMEM). Specifically, the corresponding coefficient of determination (R2) were 0.918 and 0.993. The limit of detections were 73.08 ng/mL and 131.71 ng/mL, respectively. Compared with the enzyme-linked immunosorbent assay, the hydrogel biosensor determined the concentration of MMP-9 in solution with simpler steps. This study demonstrates a novel strategy based on Fc-MG-modified hydrogels to monitor MMP-9 activity in cell secretion samples and shows the potential application in chronic wounds.


Subject(s)
Biosensing Techniques , Chitosan , Electrochemical Techniques , Ferrous Compounds , Hydrogels , Matrix Metalloproteinase 9 , Metallocenes , Chitosan/chemistry , Chitosan/analogs & derivatives , Matrix Metalloproteinase 9/metabolism , Matrix Metalloproteinase 9/analysis , Metallocenes/chemistry , Hydrogels/chemistry , Ferrous Compounds/chemistry , Biosensing Techniques/methods , Electrochemical Techniques/methods , Humans
9.
Talanta ; 275: 126124, 2024 Aug 01.
Article in English | MEDLINE | ID: mdl-38663067

ABSTRACT

Palmitic acid (PA) is a kind of saturated high fatty acid, which is involved in physiological safety and food quality. A surface molecularly imprinted polymer (MIP) electrochemical sensor was prepared on MXene surface using dopamine (DA) as functional monomer. The electrode was modified with gold nanoparticles (AuNPs), ferrocene-graphene oxide-multiwalled carbon nanotubes (Fc-GO-MWCNT) composite to enhance the electroactive area and conductivity. The sensor was characterized by scanning electron microscope (SEM), energy-dispersive X-ray spectroscopy (EDS), electrochemical impedance spectroscopy (EIS) and Differential pulse voltammetry (DPV), respectively. The parameters concerning this assay and various regeneration conditions have been carefully studied. The sensor can detect PA in the range of 1 nM-1 mM (R2 = 0.995), the limit of detection (LOD) is 0.48 nM (S/N = 3), and the limit of quantification (LOQ) is 1.61 nM. The artificial neural network (ANN) model in machine learning is further used to analyze the data collected by the sensor. The results show that the back propagation (BP) neural network in ANN is more suitable for the intelligent analysis of PA. The practicality of the sensor was confirmed by detecting PA in pork samples. This is the first MIP-based electrochemical sensor for PA, and it has great potential in practical applications.


Subject(s)
Electrochemical Techniques , Gold , Graphite , Machine Learning , Metal Nanoparticles , Nanotubes, Carbon , Palmitic Acid , Graphite/chemistry , Gold/chemistry , Nanotubes, Carbon/chemistry , Electrochemical Techniques/methods , Electrochemical Techniques/instrumentation , Palmitic Acid/analysis , Palmitic Acid/chemistry , Metal Nanoparticles/chemistry , Electrodes , Molecularly Imprinted Polymers/chemistry , Molecular Imprinting , Animals , Surface Properties , Dopamine/analysis , Ferrous Compounds/chemistry , Limit of Detection , Neural Networks, Computer , Metallocenes/chemistry
10.
Talanta ; 274: 126023, 2024 Jul 01.
Article in English | MEDLINE | ID: mdl-38583328

ABSTRACT

Dual-potential ratiometric electrochemiluminescence (ECL) is in favor of resistance to environmental interference. However, two kinds of emitters or coreactants, and a wide scan potential range (>2 V) are mandatory. This work developed a new dual-potential ratiometric ECL sensor for detection of carcinoembryonic antigen (CEA) using single emitter (luminol) and single coreactant (H2O2) with a mild potential range from -0.1 to 0.6 V. Luminol could produce a strong cathodic ECL (Ec) induced by hydroxyl radicals (HO‧) from the reduction of H2O2, and a relatively weak anodic ECL (Ea). After the ferrocene modified CEA aptamer (Apt-Fc) was attached, Fc could promote Ea by catalyzing the oxidation of H2O2, and reduce Ec by consuming HO‧. With the cycling amplification of the exonuclease I, CEA could substantially reduce the amount of Apt-Fc, resulting in the decrease of Ea and the rise of Ec. So, the ratio of Ec to Ea (Ec/Ea) was used as the detection signal, realizing the sensitive determination of CEA from 0.1 pg mL-1 to 10 ng mL-1 with a LOD of 41.85 fg mL-1 (S/N = 3). The developed sensor demonstrated excellent specificity, stability and reproducibility, with satisfactory results in practical detection.


Subject(s)
Aptamers, Nucleotide , Carcinoembryonic Antigen , Electrochemical Techniques , Hydrogen Peroxide , Luminescent Measurements , Luminol , Carcinoembryonic Antigen/analysis , Carcinoembryonic Antigen/blood , Electrochemical Techniques/methods , Humans , Luminescent Measurements/methods , Hydrogen Peroxide/chemistry , Hydrogen Peroxide/analysis , Luminol/chemistry , Aptamers, Nucleotide/chemistry , Limit of Detection , Biosensing Techniques/methods , Metallocenes/chemistry , Ferrous Compounds/chemistry
11.
Talanta ; 274: 125999, 2024 Jul 01.
Article in English | MEDLINE | ID: mdl-38583327

ABSTRACT

The construction of efficient methods for highly sensitive and rapid detection of disease markers is essential for the early diagnosis of serious diseases. In this paper, taking advantage of the UiO-66-NH2 signal molecule in combination with a waste-free entropy-driven DNA machine, a novel homogeneous electrochemical ratiometric platform is developed to detect MircoRNA (miRNA). Metal-organic framework materials (UiO-66-NH2 MOF) and ferrocene were utilized as electrochemical signal tags and reference probes, respectively. The target-initiated waste-free three-dimensional (3D) entropy-driven DNA nanomachine is activated in the presence of miRNA, resulting in DNA-labeled-UiO-66-NH2 falling off from the electrode, leading to a decrease in the signal of UiO-66-NH2 at 0.83V. Our strategy can mitigate false positive responses induced by the DNA probes immobilized on electrodes in traditional distance-dependent signal adjustment ratiometric strategies. The proposed ratiometric platform demonstrates superior sensitivity (a detection limit of 9.8 fM), simplified operation, high selectivity, and high repeatability. The ratiometric biosensor is also applied to detect miRNA content in spiked serum samples.


Subject(s)
Biosensing Techniques , Electrochemical Techniques , Entropy , Metal-Organic Frameworks , MicroRNAs , MicroRNAs/blood , MicroRNAs/analysis , Biosensing Techniques/methods , Electrochemical Techniques/methods , Humans , Metal-Organic Frameworks/chemistry , DNA/chemistry , Limit of Detection , Electrodes , DNA Probes/chemistry , DNA Probes/genetics , Ferrous Compounds/chemistry , Metallocenes/chemistry
12.
ACS Sens ; 9(4): 2141-2148, 2024 Apr 26.
Article in English | MEDLINE | ID: mdl-38578241

ABSTRACT

The glycated hemoglobin (HbA1c) level, which is defined as the ratio of HbA1c to total hemoglobin (tHb, including glycated and unglycated hemoglobin), is considered one of the preferred indicators for diabetes monitoring. Generally, assessment of the HbA1c level requires separate determination of tHb and HbA1c concentrations after a complex separation step. This undoubtedly increases the cost of the assay, and the loss or degradation of HbA1c during the separation process results in a decrease in the accuracy of the assay. Therefore, this study explored a dual-signal acquisition method for the one-step simultaneous evaluation of tHb and HbA1c. Quantification of tHb: graphene adsorbed carbon quantum dots and methylene blue were utilized as the substrate material and linked to the antibody. tHb was captured on the substrate by the antibody. The unique heme group on tHb catalyzed the production of •OH from H2O2 to degrade methylene blue on the substrate, and a quantitative relationship between the tHb concentration and the methylene blue oxidation current signal was constructed. Quantification of HbA1c: complex labels with HbA1c recognition were made of ZIF-8-ferrocene-gold nanoparticles-mercaptophenylboronic acid. The specific recognition of the boronic acid bond with the unique cis-diol structure of HbA1c establishes a quantitative relationship between the oxidation current of the label-loaded ferrocene and the concentration of HbA1c. Thus, the HbA1c level can be assessed with only one signal readout. The sensor exhibited extensive detection ranges (0.200-600 ng/mL for tHb and 0.100-300 ng/mL for HbA1c) and low detection limits (4.00 × 10-3 ng/mL for tHb and 1.03 × 10-2 ng/mL for HbA1c).


Subject(s)
Glycated Hemoglobin , Methylene Blue , Glycated Hemoglobin/analysis , Humans , Methylene Blue/chemistry , Graphite/chemistry , Gold/chemistry , Metal Nanoparticles/chemistry , Quantum Dots/chemistry , Hemoglobins/analysis , Hemoglobins/chemistry , Boronic Acids/chemistry , Ferrous Compounds/chemistry , Metallocenes/chemistry , Limit of Detection , Electrochemical Techniques/methods , Hydrogen Peroxide/chemistry
13.
Chem Commun (Camb) ; 60(36): 4773-4776, 2024 Apr 30.
Article in English | MEDLINE | ID: mdl-38602162

ABSTRACT

A small-molecule Fenton reagent, integrating ferrocene with a carbonic anhydrase inhibitor, was designed to intelligently regulate intracellular acidosis for self-augmented chemodynamic therapy. Acidosis coupled with up-regulated ROS levels demonstrated potent cytotoxicity and effective tumor suppression.


Subject(s)
Ferrous Compounds , Hydrogen Peroxide , Iron , Metallocenes , Humans , Ferrous Compounds/chemistry , Ferrous Compounds/pharmacology , Hydrogen Peroxide/chemistry , Hydrogen Peroxide/pharmacology , Iron/chemistry , Metallocenes/chemistry , Metallocenes/pharmacology , Reactive Oxygen Species/metabolism , Carbonic Anhydrase Inhibitors/chemistry , Carbonic Anhydrase Inhibitors/pharmacology , Acidosis/drug therapy , Animals , Antineoplastic Agents/chemistry , Antineoplastic Agents/pharmacology , Antineoplastic Agents/chemical synthesis , Cell Line, Tumor , Mice
14.
Biosensors (Basel) ; 14(4)2024 Mar 28.
Article in English | MEDLINE | ID: mdl-38667154

ABSTRACT

We designed and optimized a glucose biosensor system based on a screen-printed electrode modified with the NAD-GDH enzyme. To enhance the electroactive surface area and improve the electron transfer efficiency, we introduced graphene oxide (GO) and ferrocene-modified linear poly(ethylenimine) (LPEI-Fc) onto the biosensor surface. This strategic modification exploits the electrostatic interaction between graphene oxide, which possesses a negative charge, and LPEI-Fc, which is positively charged. This interaction results in increased catalytic current during glucose oxidation and helps improve the overall glucose detection sensitivity by amperometry. We integrated the developed glucose sensor into a flow injection (FI) system. This integration facilitates a swift and reproducible detection of glucose, and it also mitigates the risk of contamination during the analyses. The incorporation of an FI system improves the efficiency of the biosensor, ensuring precise and reliable results in a short time. The proposed sensor was operated at a constant applied potential of 0.35 V. After optimizing the system, a linear calibration curve was obtained for the concentration range of 1.0-40 mM (R2 = 0.986). The FI system was successfully applied to determine the glucose content of a commercial sports drink.


Subject(s)
Biosensing Techniques , Ferrous Compounds , Glucose , Graphite , Metallocenes , Polyethyleneimine , Graphite/chemistry , Metallocenes/chemistry , Ferrous Compounds/chemistry , Polyethyleneimine/chemistry , Glucose/analysis , Electrodes , Oxidation-Reduction
15.
Eur J Med Chem ; 271: 116429, 2024 May 05.
Article in English | MEDLINE | ID: mdl-38663284

ABSTRACT

Amodiaquine (AQ) is a potent antimalarial drug used in combination with artesunate as part of artemisinin-based combination therapies (ACTs) for malarial treatment. Due to the rising emergence of resistant malaria parasites, some of which have been reported for ACT, the usefulness of AQ as an efficacious therapeutic drug is threatened. Employing the organometallic hybridisation approach, which has been shown to restore the antimalarial activity of chloroquine in the form of an organometallic hybrid clinical candidate ferroquine (FQ), the present study utilises this strategy to modulate the biological performance of AQ by incorporating ferrocene. Presently, we have conceptualised ferrocenyl AQ derivatives and have developed facile, practical routes for their synthesis. A tailored library of AQ derivatives was assembled and their antimalarial activity evaluated against chemosensitive (NF54) and multidrug-resistant (K1) strains of the malaria parasite, Plasmodium falciparum. The compounds generally showed enhanced or comparable activities to those of the reference clinical drugs chloroquine and AQ, against both strains, with higher selectivity for the sensitive phenotype, mostly in the double-digit nanomolar IC50 range. Moreover, representative compounds from this series show the potential to block malaria transmission by inhibiting the growth of stage II/III and V gametocytes in vitro. Preliminary mechanistic insights also revealed hemozoin inhibition as a potential mode of action.


Subject(s)
Amodiaquine , Antimalarials , Ferrous Compounds , Metallocenes , Plasmodium falciparum , Antimalarials/pharmacology , Antimalarials/chemistry , Antimalarials/chemical synthesis , Ferrous Compounds/chemistry , Ferrous Compounds/pharmacology , Plasmodium falciparum/drug effects , Metallocenes/chemistry , Metallocenes/pharmacology , Amodiaquine/pharmacology , Amodiaquine/chemistry , Structure-Activity Relationship , Molecular Structure , Humans , Parasitic Sensitivity Tests , Dose-Response Relationship, Drug
16.
ACS Macro Lett ; 13(5): 475-482, 2024 May 21.
Article in English | MEDLINE | ID: mdl-38591821

ABSTRACT

The development of antioxidant wound dressings to remove excessive free radicals around wounds is essential for wound healing. In this study, we developed an efficient strategy to prepare antioxidant self-healing hydrogels as wound dressings by combining multicomponent reactions (MCRs) and postpolymerization modification. A polymer containing ferrocene and phenylboronic acid groups was developed via the Biginelli reaction, followed by efficient modification. This polymer is antioxidant due to its ferrocene moieties and can rapidly cross-link poly(vinyl alcohol) to realize an antioxidant self-healing hydrogel through dynamic borate ester linkages. This hydrogel has low cytotoxicity and is biocompatible. In in vivo experiments, this hydrogel is superior to existing clinical dressings in promoting wound healing. This study demonstrates the value of the Biginelli reaction in exploring biomaterials, potentially offering insights into the design of other multifunctional polymers and related materials using different MCRs.


Subject(s)
Antioxidants , Ferrous Compounds , Hydrogels , Metallocenes , Wound Healing , Ferrous Compounds/chemistry , Metallocenes/chemistry , Hydrogels/chemistry , Hydrogels/pharmacology , Wound Healing/drug effects , Antioxidants/pharmacology , Antioxidants/chemistry , Animals , Mice , Boronic Acids/chemistry , Polyvinyl Alcohol/chemistry , Humans , Biocompatible Materials/chemistry , Biocompatible Materials/pharmacology
17.
Chirality ; 36(3): e23653, 2024 Mar.
Article in English | MEDLINE | ID: mdl-38403899

ABSTRACT

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.


Subject(s)
Antineoplastic Agents , Ferrous Compounds , Phenethylamines , Metallocenes/pharmacology , Metallocenes/chemistry , Cell Line, Tumor , Stereoisomerism , Antineoplastic Agents/pharmacology , Antineoplastic Agents/chemistry
18.
Food Chem ; 441: 138333, 2024 May 30.
Article in English | MEDLINE | ID: mdl-38185050

ABSTRACT

A sensitive signal-on photoelectrochemical aptasensor for antibiotic determination was constructed based on the energy level matching between ferrocene and CuInS2. P-type CuInS2 microflower was complexed with reduced graphene oxide (CuInS2/rGO) to get photocathode current with good photoelectric conversion efficiency and stability. Then, hairpin DNA (HP) was covalently bonded to the electrode surface. A triple helix DNA (THMS) was used as a molecular switch. After the specific recognition between target and THMS in homogeneous solution, ferrocene labeled probe (Fc-T2) was released. Finally, Fc-T2 was captured by the HP, which leaded the obvious increase of photocurrent for the energy level matching between ferrocene and CuInS2. The increase of the photocurrent signal was proportional to the concentration of target amoxicillin (AMOX), the linear range was 100 fM-100 nM with detection limit of 19.57 fM. Meanwhile, the method has been successfully applied for milk and lake water samples analysis with satisfactory results.


Subject(s)
Aptamers, Nucleotide , Biosensing Techniques , Ferrous Compounds , Anti-Bacterial Agents , Amoxicillin , Biosensing Techniques/methods , Metallocenes/chemistry , Electrochemical Techniques/methods , DNA/chemistry , Aptamers, Nucleotide/chemistry , Limit of Detection
19.
Anal Chem ; 95(48): 17920-17927, 2023 12 05.
Article in English | MEDLINE | ID: mdl-37983085

ABSTRACT

We demonstrate for the first time the construction of a dual-mode biosensor for electrochemiluminescent (ECL) and electrochemical chiral recognition of l- and d-isomers of amino acids, with ferrocene (Fc) as both a signal enhancer and a signal tracer. With the dissolved oxygen as a coreactant, ZnIn2S4 acts as the ECL emitter to generate a weak cathodic ECL signal. Fc can enter into the ß-cyclodextrin (ß-CD) cavity on ZnIn2S4-modified electrode as a result of host-guest interaction. Since Fc can promote H2O and O2 to produce abundant reactive oxygen species (ROS) (e.g., O2·- and ·OH), the ECL signal of ZnIn2S4 can be further amplified with Fc as a coreaction accelerator. Meanwhile, Fc molecules on the ß-CD/ZnIn2S4-modified electrode can be electrochemically oxidized to Fc+ to produce a remarkable oxidation peak current. When l-histidine (l-His) is present, the matching of the l-His configuration with the ß-CD cavity leads to the entrance of more l-His into the cavity of ß-CD than d-histidine (d-His), and the subsequent competence of l-His with Fc on the Fc/ß-CD/ZnIn2S4-modified electrode induces the decrease in both Fc peak current and ZnIn2S4-induced ECL intensity. This dual-mode biosensor can efficiently discriminate l-His from d-His, and it can sensitively monitor l-His with a detection limit of 7.60 pM for ECL mode and 3.70 pM for electrochemical mode. Moreover, this dual-mode biosensor can selectively discriminate l-His from other l- and d-isomers (e.g., threonine, phenylalanine, and glutamic acid), with potential applications in the chiral recognition of nonelectroactive chiral compounds, bioanalysis, and disease diagnosis.


Subject(s)
Biosensing Techniques , Luminescent Measurements , Metallocenes/chemistry , Stereoisomerism , Electrochemical Techniques , Limit of Detection
20.
Mikrochim Acta ; 190(11): 432, 2023 10 09.
Article in English | MEDLINE | ID: mdl-37806989

ABSTRACT

An ochratoxin A (OTA) electrochemical biosensor based on a cascade signal amplification strategy with Ag nanoparticles (AgNPs) and ring opening polymerization (ROP) was constructed. The large specific surface area of AgNPs was used to increase the loading of OTA aptamer on the electrode surface, enhancing the ability to capture OTA as a way to achieve the first signal amplification. The OTA antibody modified with polyethylenimine specifically recognizes the OTA, forming an aptamer-OTA-antibody sandwich structure. The amino group on polyethylenimine initiates the ROP reaction with α-amino acid-n-carboxylic anhydride-ferrocene (NCA-Fc) as the monomer. A large number of electrochemical signal units of ferrocene are introduced into the sensing system for a second signal amplification. By amplifying the signal twice, the sensitivity of the sensor is improved. Under the optimal conditions, the detection range of the sensor is 1 pg·mL-1 ~ 1 µg·mL-1, while the detection limit is as low as 117 fg·mL-1. Moreover, the sensor has the advantages of high sensitivity, good stability and selectivity. Standard addition recovery experiment proved that the sensing system can be successfully used for the detection of OTA in four actual samples with recoveries in the range 90.0 to 113% with RSDs of 0.6 to 5.2%, providing a new idea for the pollution assessment of mycotoxins.


Subject(s)
Biosensing Techniques , Metal Nanoparticles , Metallocenes/chemistry , Metal Nanoparticles/chemistry , Polyethyleneimine , Polymerization , Electrochemical Techniques , Silver
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