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1.
Talanta ; 281: 126935, 2025 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-39332047

RESUMO

The ideal photoelectrode and efficient signaling strategy are pivotal to achieve sensitive photoelectrochemical (PEC) analysis. Here, a multipath collaborative signal amplification-based PEC immunosensor was constructed for the ultrasensitive detection of cytokeratin 19 fragment 21-1. Specifically, the photoelectrode fabricated by Z-scheme In2O3/g-C3N4 heterojunction showed enhanced photocurrent intensity in response to visible light. Meanwhile, the signal probe, horseradish peroxidase functionalized dopamine-melanin nanosphere@Au nanoparticles (HRP-Dpa-melanin NS@AuNPs), were introduced into the system. When the target exists, the signal probe can induce multiple quenching of the photocurrent due to the competition of light absorption, steric hindrance and HRP-mediated biocatalytic precipitation, which effectively inhibit light, electron donor, and electron access to the photoelectrode. The fabricated immunosensor exhibits a wide linear range from 1.0 × 10-3 - 1.0 × 102 ng mL-1 with the detection limit of 0.35 pg mL-1 (S/N = 3) for cytokeratin 19 fragment 21-1 detection. The study enhances sensitivity for PEC detection by utilizing the superior Z-scheme heterojunction photoelectrode, providing a valuable method that combines multiple signal pathways for a synergistic effect in bioanalysis.


Assuntos
Técnicas Eletroquímicas , Índio , Técnicas Eletroquímicas/métodos , Imunoensaio/métodos , Humanos , Índio/química , Nitrilas/química , Processos Fotoquímicos , Eletrodos , Limite de Detecção , Queratina-19/análise , Técnicas Biossensoriais/métodos , Nanopartículas Metálicas/química , Ouro/química , Compostos de Nitrogênio/química , Grafite/química , Peroxidase do Rábano Silvestre/química
2.
J Environ Sci (China) ; 150: 657-675, 2025 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-39306437

RESUMO

The uncontrolled release of antibiotics into the environment would be extremely harmful to human health and ecosystems. Therefore, it is in urgent need to monitor the environment and promote the detection and degradation of antibiotics to the relatively harmless by-products to a feasible extent. Graphitic carbon nitride (g-C3N4) is a non-metallic n-type semiconductor that can be used for the antibiotic detection and degradation due to its easy synthesis process, excellent chemical stability and unique optical properties. Unfortunately, the utilization of visible light, electron-hole recombination and electron conductivity have hindered its potential applications in the fields of photocatalytic degradation and electrochemical detection. Although previous publications have highlighted the diverse modification methods for the g-C3N4-based materials, the underlying structure-performance relationships of g-C3N4, especially for the detection and degradation of antibiotics, remains to be further explored. In view of this, the current review centered on the recent progress in the modification techniques of g-C3N4, the detection and degradation of antibiotics using the g-C3N4-based materials, as well as the potential antibiotic degradation mechanisms of the g-C3N4-based materials. Additionally, the underlying applications of the g-C3N4-based materials for antibiotic detection and degradation were also prospected. This review would provide a valuable research foundation and the up-to-date information for the g-C3N4-based materials to combat antibiotic pollution in the environment.


Assuntos
Antibacterianos , Grafite , Compostos de Nitrogênio , Grafite/química , Antibacterianos/análise , Antibacterianos/química , Compostos de Nitrogênio/química , Compostos de Nitrogênio/análise , Monitoramento Ambiental/métodos , Nitrilas/química , Nitrilas/análise
3.
J Environ Sci (China) ; 151: 505-515, 2025 May.
Artigo em Inglês | MEDLINE | ID: mdl-39481956

RESUMO

N-participated lignin depolymerization is of great importance for the transformation of waste lignin into value-added chemicals. The vast majority of developed strategies employ organic amines as nitrogen source, and considerable methods rely on excessive use of strong base, which suffers severe environmental issues. Herein, benzonitrile derivatives are synthesized from oxidized lignin ß-O-4 model compounds in the presence of solid nitrogen source (NH4)2CO3 under mild, base-free conditions over commercially available copper catalyst. Mechanism studies suggest the transformation undergoes a one-pot, highly coupled cascade reaction path involving oxidative C-C bond cleavage and in-situ formation of CN bond. Of which, Cu(OAc)2 catalyzes the transfer of hydrogen from Cß (Cß-H) to Cα, leading to the cleavage of Cα-Cß bonds to offer benzaldehyde derivative, this intermediate then reacts in-situ with (NH4)2CO3 to afford the targeted aromatic nitrile product. Tetrabutylammonium iodide (TBAI), acting as a promoter, plays a key role in breaking the Cα-Cß bonds to form the intermediate benzaldehyde derivative. With this protocol, the feasibility of the production of value-added syringonitrile from birchwood lignin has been demonstrated. This transformation provides a sustainable approach to benzonitrile chemicals from renewable source of lignin.


Assuntos
Cobre , Lignina , Nitrilas , Lignina/química , Nitrilas/química , Catálise , Cobre/química
4.
Food Chem ; 463(Pt 1): 141121, 2025 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-39255709

RESUMO

Electrochemical sensors have a broad range of industrial applications due to their sensitivity, speed, and cost-effectiveness. These sensors enable the continuous monitoring and control of critical parameters in various industrial processes. For instance, they are essential in food safety, environmental monitoring, biomedical applications, and pharmaceutical production. In the food industry, electrochemical sensors facilitate the rapid and reliable detection of contaminants and pathogens in food products, thus enhancing product quality and consumer safety. An electrochemical sensor was developed with the molecularly imprinted polymer (MIP) technique to detect deltamethrin with high sensitivity and selectivity. The sensor was fabricated by electrodeposition of Co3O4 on indium tin oxide (ITO), followed by electropolymerization of o-phenylenediamine with deltamethrin as a template molecule. The template molecules were then removed from the modified electrode by a methanol. The MIP-based electrochemical sensor exhibited high sensitivity and selectivity towards deltamethrin. Under the optimized conditions, the LOD values for the MIP/Co3O4/ITO electrode in the first and second linear regressions were 1.53 nM for linear range of 2.82 nM to 56.5 nM and 0.34 µM for linear range of 0.25 µM to 3.98 µM. Moreover, the LOD values for the NIP/Co3O4/ITO electrode in the first and second regressions were 2.43 nM for the linear range of 3.91 nM to 65.0 nM and 726.0 nM for the linear range of 0.023 µM to 4.5 µM. The developed electrochromic pesticide sensor, being an electrochemical-based molecularly imprinted polymer (MIP) sensor incorporating electrochromic materials, enables both target-specific pesticide detection and visual pesticide identification based on color changes dependent on pesticide concentration. Consequently, this system is more advantageous compared to electrochemical-based MIP sensors, as it provides both qualitative and quantitative determinations. The qualitative assessment aims to enhance the ease of use of the sensor, thereby increasing the potential for it to become a commercially viable product by reducing the need for instrumental devices.


Assuntos
Técnicas Eletroquímicas , Polímeros Molecularmente Impressos , Nitrilas , Piretrinas , Piretrinas/análise , Nitrilas/química , Nitrilas/análise , Técnicas Eletroquímicas/instrumentação , Técnicas Eletroquímicas/métodos , Polímeros Molecularmente Impressos/química , Contaminação de Alimentos/análise , Impressão Molecular , Polímeros/química , Inseticidas/análise , Limite de Detecção
5.
J Colloid Interface Sci ; 678(Pt B): 1169-1180, 2025 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-39288712

RESUMO

The MnO2/CN S-scheme heterojunctions were prepared using the hydrothermal method, which significantly promoted periodate (PI) activation for the TC removal. Notably, the MnO2/CN-0.1 achieved a TC removal rate of 79.7 % within 25 min in the PI/Vis system, which was 1.39 and 3.68 times that of MnO2 and g-C3N4, respectively. The improved TC degradation performance could be attributed to the synergetic effect of photothermal effect of MnO2 and the S-scheme heterojunction. On the basis of the infrared thermography images, the photothermal properties of MnO2 could increase temperatures of the reaction system, leading to the promotion of the PI activation. The formation of the MnO2/CN S-scheme not only effectively suppressed charge recombination, but also facilitated the Mn(IV)/Mn(III) redox cycle within the reaction. Under different pH and anion conditions, the MnO2/CN-0.1/PI system exhibited excellent capability in TC removal. Additionally, the toxicity of the degraded solution was evaluated based on the LC-MS test results and the growth experiment of Mung bean seeds. This work put forward an efficient approach on S-scheme photothermal catalysts to achieve efficient utilization of PI on TC degradation, which demonstrates a promising method for photothermal assistance PI activation to remediate the water environment efficiently.


Assuntos
Compostos de Manganês , Óxidos , Tetraciclina , Compostos de Manganês/química , Óxidos/química , Catálise , Tetraciclina/química , Poluentes Químicos da Água/química , Poluentes Químicos da Água/isolamento & purificação , Processos Fotoquímicos , Tamanho da Partícula , Propriedades de Superfície , Nitrilas/química , Temperatura , Grafite/química , Compostos de Nitrogênio/química
6.
J Environ Sci (China) ; 148: 437-450, 2025 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-39095178

RESUMO

For environmental applications, it is crucial to rationally design and synthesize photocatalysts with positive exciton splitting and interfacial charge transfer. Here, a novel Ag-bridged dual Z-scheme Ag/g-C3N4/CoNi-LDH plasmonic heterojunction was successfully synthesized using a simple method, with the goal of overcoming the common drawbacks of traditional photocatalysts such as weak photoresponsivity, rapid combination of photo-generated carriers, and unstable structure. These materials were characterized by XRD, FT-IR, SEM, TEM UV-Vis/DRS, and XPS to verify the structure and stability of the heterostructure. The pristine LDH, g-C3N4, and Ag/g-C3N4/CoNi-LDH composite were investigated as photocatalysts for water remediation, an environmentally motivated process. Specifically, the photocatalytic degradation of tetracycline was studied as a model reaction. The performance of the supports and composite catalyst were determined by evaluating both the degradation and adsorption phenomenon. The influence of several experimental parameters such as catalyst loading, pH, and tetracycline concentration were evaluated. The current study provides important data for water treatment and similar environmental protection applications.


Assuntos
Nanocompostos , Fotólise , Prata , Poluentes Químicos da Água , Purificação da Água , Nanocompostos/química , Poluentes Químicos da Água/química , Purificação da Água/métodos , Prata/química , Catálise , Nitrilas/química , Compostos de Nitrogênio/química , Adsorção , Grafite
7.
J Environ Sci (China) ; 149: 188-199, 2025 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-39181633

RESUMO

Photocatalytic disinfection is an eco-friendly strategy for countering bacterial pollution in aquatic environments. Numerous strategies have been devised to facilitate the generation of reactive oxygen species (ROS) within photocatalysts, ultimately leading to the eradication of bacteria. However, the significance of the physical morphology of photocatalysts in the context of sterilization is frequently obscured, and the progress in the development of physical-chemical synergistic sterilization photocatalysts has been relatively limited. Herein, graphitic carbon nitride (g-C3N4) is chemically protonated to expose more sharp edges. PL fluorescence and EIS results indicate that the protonation can accelerate photogenerated carrier separation and enhance ROS production. Meanwhile, the sharp edges on the protonated g-C3N4 facilitate the physical disruption of cell walls for further promoting oxidative damage. Protonated C3N4 demonstrated superior bactericidal performance than that of pristine g-C3N4, effectively eliminating Escherichia coli within 40 minutes under irradiation. This work highlights the significance of incorporating physical and chemical synergies in photocatalyst design to enhance the disinfection efficiency of photocatalysis.


Assuntos
Desinfecção , Nitrilas , Nitrilas/química , Desinfecção/métodos , Catálise , Escherichia coli/efeitos dos fármacos , Espécies Reativas de Oxigênio , Grafite/química , Esterilização/métodos , Compostos de Nitrogênio/química
8.
J Environ Sci (China) ; 149: 512-523, 2025 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-39181663

RESUMO

Oxygen activation leading to the generation of reactive oxygen species (ROS) is essential for photocatalytic environmental remediation. The limited efficiency of O2 adsorption and reductive activation significantly limits the production of ROS when employing C3N4 for the degradation of emerging pollutants. Doping with metal single atoms may lead to unsatisfactory efficiency, due to the recombination of photogenerated electron-hole pairs. Here, Mn and S single atoms were introduced into C3N4, resulting in the excellent photocatalytic performances. Mn/S-C3N4 achieved 100% removal of bisphenol A, with a rate constant 11 times that of pristine C3N4. According to the experimental results and theoretical simulations, S-atoms restrict holes, facilitating the photo-generated carriers' separation. Single-atom Mn acts as the O2 adsorption site, enhancing the adsorption and activation of O2, resulting the generation of ROS. This study presents a novel approach for developing highly effective photocatalysts that follows a new mechanism to eliminate organic pollutants from water.


Assuntos
Oxigênio , Poluentes Químicos da Água , Poluentes Químicos da Água/química , Oxigênio/química , Catálise , Manganês/química , Compostos Benzidrílicos/química , Nitrilas/química , Adsorção , Espécies Reativas de Oxigênio , Recuperação e Remediação Ambiental/métodos , Fenóis/química
9.
Mikrochim Acta ; 191(11): 678, 2024 10 17.
Artigo em Inglês | MEDLINE | ID: mdl-39420129

RESUMO

Methidathion (MTDT), a common organophosphorus pesticide with high insecticidal activity, is widely used for pest control. However, the misuse of MTDT leads to widespread residues and endangers human health. Therefore, it is crucial to develop a simple and highly sensitive method for the detection of MTDT residues. Herein, ZIF-90/MnO2/g-C3N4/Fe3O4 composite particles were synthesized: The  MnO2 nanosheets could absorb the energy of the excited g-C3N4 to quench the ECL of g-C3N4 while ZIF-90 acted as a mimetic enzyme to catalyze the formation of thiocholine from MTDT. The thiocholine caused the reduction of MnO2 to Mn2+, restoring the ECL signal of g-C3N4. Combined with molecular imprinting technique, an electrochemiluminescence sensor was constructed for the determination of MTDT. The determination range was 1.00 × 10-9 ~ 7.00 × 10-7 g/L, and the detection limit was 6.58 × 10-10 g/L. Structurally similar organophosphorus pesticides showed no cross-reactivity. The method has high sensitivity and specificity, and has been successfully applied to the determination of MTDT residue in fruits with recoveries in the range 93.75% ~ 102.37%.


Assuntos
Técnicas Eletroquímicas , Limite de Detecção , Medições Luminescentes , Compostos de Manganês , Compostos Organotiofosforados , Óxidos , Compostos de Manganês/química , Técnicas Eletroquímicas/métodos , Medições Luminescentes/métodos , Óxidos/química , Compostos Organotiofosforados/análise , Compostos Organotiofosforados/química , Impressão Molecular , Grafite/química , Zeolitas/química , Inseticidas/análise , Compostos de Nitrogênio/química , Nanopartículas de Magnetita/química , Nitrilas/química
10.
Chem Res Toxicol ; 37(10): 1747-1754, 2024 Oct 21.
Artigo em Inglês | MEDLINE | ID: mdl-39367858

RESUMO

This study addressed the development of a novel biomarker for 2-chlorobenzalmalononitrile (CS) gas exposure. Using liquid chromatographic and mass spectrometric techniques, we found that CS underwent rapid hydrolysis into 2-chlorobenzaldehyde (2-CBA), a highly reactive intermediate that reacted swiftly with endogenous cysteine (Cys) and Cys residues in proteins, producing a stable 2-(2-chlorophenyl)thiazolidine-4-carboxylic acid adduct (ClPh-SPro) in high yield, which may be used as a CS exposure dosimeter. In particular, it was found that most CS was rapidly hydrolyzed under physiologically relevant conditions, with over 90% of CS being converted into 2-CBA in as short as 20 min. The resultant 2-CBA then reacted swiftly with Cys (k = 0.086 M-1 s-1), forming the stable thiazolidine-4-carboxylic acid adduct, which was detected both in the intracellular fluid and in the cell-isolated proteins of CS-exposed lung cells, as well as in purified human serum albumin. It is expected that the results of this study will facilitate exposure assessment for bystanders who may have been exposed to high levels of CS gas unwillingly.


Assuntos
Biomarcadores , Nitrilas , Tiazolidinas , Tiazolidinas/química , Humanos , Nitrilas/química , Nitrilas/análise , Biomarcadores/análise , Estrutura Molecular
11.
Sci Rep ; 14(1): 22897, 2024 10 02.
Artigo em Inglês | MEDLINE | ID: mdl-39358462

RESUMO

Antibiotics are extensively used in human medicine, aquaculture, and animal husbandry, leading to the release of antimicrobial resistance into the environment. This contributes to the rapid spread of antibiotic-resistant genes (ARGs), posing a significant threat to human health and aquatic ecosystems. Conventional wastewater treatment methods often fail to eliminate ARGs, prompting the adoption of advanced oxidation processes (AOPs) to address this growing risk. The study investigates the efficacy of visible light-driven photocatalytic systems utilizing two catalyst types (TiO2-Pd/Cu and g-C3N4-Pd/Cu), with a particular emphasis on their effectiveness in eliminating blaTEM, ermB, qnrS, tetM. intl1, 16 S rDNA and 23 S rDNA through photocatalytic ozonation and peroxone processes. Incorporating O3 into photocatalytic processes significantly enhances target removal efficiency, with the photocatalyst-assisted peroxone process emerging as the most effective AOP. The reemergence of targeted contaminants following treatment highlights the pivotal importance of AOPs and the meticulous selection of catalysts in ensuring sustained treatment efficacy. Furthermore, Polymerase Chain Reaction-Denaturing Gradient Gel Electrophoresis (PCR-DGGE) analysis reveals challenges in eradicating GC-rich bacteria with TiO2 and g-C3N4 processes, while slight differences in Cu/Pd loadings suggest g-C3N4-based ozonation improved antibacterial effectiveness. Terminal Restriction Fragment Length Polymorphism analysis highlights the efficacy of the photocatalyst-assisted peroxone process in treating diverse samples.


Assuntos
Titânio , Titânio/química , Titânio/farmacologia , Catálise , Águas Residuárias/microbiologia , Águas Residuárias/química , Antibacterianos/farmacologia , Antibacterianos/química , Purificação da Água/métodos , Ozônio/química , Ozônio/farmacologia , Resistência Microbiana a Medicamentos/genética , Compostos de Nitrogênio/química , Luz , Nitrilas/química , Nitrilas/farmacologia , Cobre/química , Cobre/farmacologia , Genes Bacterianos , Farmacorresistência Bacteriana/genética , Oxirredução , Grafite
12.
PLoS One ; 19(10): e0312891, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39480779

RESUMO

The durability and mechanical properties of synthetic medical gloves, such as those made from nitrile, vary drastically depending on the manufacturer. This study reports the chemical composition of several brands of nitrile gloves via FTIR and solid-state NMR analysis and relates composition to glove durability (found via GAD), mechanical performance (found via Instron), and whether the gloves meet or fail ASTM International standards. Out of the four nitrile examination glove brands tested, American Nitrile Slate brand had superior durability results and was found to be made of acrylonitrile butadiene rubber, as expected. The U.S. Medical glove brand, which was also found to be pure nitrile, had the superior tensile results, consistently reaching over 800% elongation before breaking. Although Restore Touch brand exam gloves were made of nitrile, they exhibited substandard tensile strength and durability due to the thinness of the glove, which barely met the ASTM minimum thickness value. The Vglove brand glove had the overall worst mechanical properties, did not meet ASTM requirements, and had an NMR spectrum consistent with that of a polyvinyl chloride glove, rather than nitrile. Gloves that fail to meet the minimum performance requirements should not be used for medical purposes to protect the health and safety of consumers.


Assuntos
Nitrilas , Nitrilas/química , Nitrilas/análise , Resistência à Tração , Teste de Materiais/métodos , Luvas Protetoras/normas , Embalagem de Produtos/normas , Luvas Cirúrgicas , Espectroscopia de Infravermelho com Transformada de Fourier/métodos , Espectroscopia de Ressonância Magnética/métodos , Humanos
13.
ACS Appl Mater Interfaces ; 16(43): 58299-58312, 2024 Oct 30.
Artigo em Inglês | MEDLINE | ID: mdl-39432433

RESUMO

Catechol-O-methyltransferase inhibitors (iCOMT), such as entacapone, have been successfully employed to treat tremor-related symptoms of Parkinson's disease. However, iCOMT has been associated with a short half-life and poor oral bioavailability. Nanobased drug delivery systems have often been used to overcome this type of setbacks. Therefore, entacapone was encapsulated in PEGylated poly(lactic-co-glycolic acid) (PLGA)-based nanoparticles (NPs) via a nanoprecipitation process, as well as in PEGylated nanostructured lipid carriers (NLCs) using a solvent emulsification/evaporation method. Both nanoformulations presented sub-200 nm populations, with zeta-potential (ZP) values close to -30 mV, and showed stability at different pHs, while maintaining their physicochemical properties mostly intact, presenting only a change in their superficial charge (ZP values), indicating their interaction. Both nanoformulations presented interaction with mucins, which anticipates good permeation and bioavailability for oral and topical administration. No cytotoxic effects were observed for lyophilized PLGA NPs encapsulating entacapone, in which 2-hydroxypropyl-ß-cyclodextrin (HPßCD) was used as a cryoprotectant at 3% concentration (HP-PLGA@Ent), in human hepatocellular carcinoma (HepG2), human neuroblastoma (SH-SY5Y), or human epithelial colorectal adenocarcinoma (Caco-2) cell lines. Conversely, NLCs encapsulating entacapone (W-NLCs@Ent) presented cytotoxic effects on the HepG2 cell line, likely due to intracellular lipid accumulation or storage. Both nanoformulations maintained a COMT inhibition effect in HepG2 cells, using 3-BTD as the COMT probe. An increase of entacapone permeability in both monolayer and coculture models (Caco-2 and Caco-2/HT29-MTX, respectively) was observed for the developed nanoformulations. Overall, this work shows that encapsulated entacapone in different nanocarriers could be a stimulating alternative to solve entacapone setbacks, since they improve its physicochemical properties and permeability while still maintaining the COMT inhibitory activity.


Assuntos
Disponibilidade Biológica , Catecóis , Portadores de Fármacos , Nanopartículas , Nitrilas , Humanos , Nanopartículas/química , Portadores de Fármacos/química , Catecóis/química , Nitrilas/química , Nitrilas/farmacologia , Copolímero de Ácido Poliláctico e Ácido Poliglicólico/química , Células CACO-2 , Inibidores de Catecol O-Metiltransferase/química , Inibidores de Catecol O-Metiltransferase/farmacologia , Polietilenoglicóis/química , Permeabilidade/efeitos dos fármacos
14.
Mikrochim Acta ; 191(11): 706, 2024 10 29.
Artigo em Inglês | MEDLINE | ID: mdl-39467865

RESUMO

A highly sensitive, portable, rapid, and accurate colorimetric sensing method is presented. It is based upon exfoliated g-C3N4 nanosheets (E-g-C3N4 NSs), having peroxidase nanozyme-like properties. The as-prepared catalyst (E-g-C3N4 NSs) tends to oxidize the colorless tetramethyl-benzidine (TMB) into oxidized-TMB in the presence of hydrogen peroxide (H2O2) generating a dark blue color and corresponding ultraviolet visible-spectral changes following a Michaelis-Menten kinetic. The prepared colorimetric sensor exhibited response within the range 0.001-0.450 µM having R2 value of 0.999 and a detective limit (LOD) of 0.15 ± 0.04 nM. Furthermore, the sensor also displayed outstanding selectivity, ample stability (10 weeks), and excellent practicability in real sample applications. All these outstanding properties were highly attributed to the large surface area with exposed actives sites, high surface energy, and large conductive structure of E-g-C3N4 NSs. For comparison of the catalytic study, we have also explored the sensing mechanism of B-g-C3N4, using the same optimized experimental conditions. Resultantly, we concluded that the proposed sensor (E-g-C3N4 NSs) will gain considerable attention for on-site environmental and health monitoring in future endeavor.


Assuntos
Benzidinas , Colorimetria , Peróxido de Hidrogênio , Limite de Detecção , Nanoestruturas , Colorimetria/métodos , Peróxido de Hidrogênio/química , Peróxido de Hidrogênio/análise , Nanoestruturas/química , Benzidinas/química , Catálise , Compostos de Nitrogênio/química , Nitrilas/química , Oxirredução , Peroxidase/química , Peroxidase/metabolismo , Grafite/química
15.
Methods Enzymol ; 704: 143-172, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39300646

RESUMO

The isonitrile group is a compact, electron-rich moiety coveted for its commonplace as a building block and bioorthogonal functionality in synthetic chemistry and chemical biology. Hundreds of natural products containing an isonitrile group with intriguing bioactive properties have been isolated from diverse organisms. Our recent discovery of a conserved biosynthetic gene cluster in some Actinobacteria species highlighted a novel enzymatic pathway to isonitrile formation involving a non-heme iron(II) and α-ketoglutarate-dependent dioxygenase. Here, we focus this chapter on recent advances in understanding and probing the biosynthetic machinery for isonitrile synthesis by non-heme iron(II) and α-ketoglutarate-dependent dioxygenases. We will begin by describing how to harness isonitrile enzymatic machinery through heterologous expression, purification, synthetic strategies, and in vitro biochemical/kinetic characterization. We will then describe a generalizable strategy to probe the mechanism for isonitrile formation by combining various spectroscopic methods. The chapter will also cover strategies to study other enzyme homologs by implementing coupled assays using biosynthetic pathway enzymes. We will conclude this chapter by addressing current challenges and future directions in understanding and engineering isonitrile synthesis.


Assuntos
Nitrilas , Nitrilas/metabolismo , Nitrilas/química , Ácidos Cetoglutáricos/metabolismo , Oxirredutases/metabolismo , Oxirredutases/genética , Oxirredutases/química , Família Multigênica , Proteínas de Bactérias/genética , Proteínas de Bactérias/metabolismo , Proteínas de Bactérias/química , Ferro/metabolismo , Ferro/química , Vias Biossintéticas , Dioxigenases/metabolismo , Dioxigenases/genética , Dioxigenases/química , Cinética , Actinobacteria/enzimologia , Actinobacteria/genética , Actinobacteria/metabolismo
16.
Zhongguo Ying Yong Sheng Li Xue Za Zhi ; 40: e20240027, 2024 Sep 29.
Artigo em Inglês | MEDLINE | ID: mdl-39341725

RESUMO

OBJECTIVE: Bosutinib (BST) is a Biopharmaceutics Classification System Class II drug having very low solubility and high permeability. Low aqueous solubility and poor dissolution of BST lead to poor bioavailability, Thus, limited aqueous solubility is the bottleneck for the therapeutic outcome of BST. Animal data suggest that the absolute bioavailability of BST is about 14-34% due to an extensive first-pass effect. To overcome hepatic first-pass metabolism and to enhance oral bioavailability, lipid-based drug delivery systems such as solid lipid nanoparticles (SLNs) can be used. METHODS: SLNs are submicron colloidal carriers having a size range of 50-1000 nm. These are prepared with physiological lipid and dispersed in water or aqueous surfactant solution. BST can be conveniently loaded into SLNs to improve the oral bioavailability by exploiting the intestinal lymphatic transport. An optimal system was evaluated for bioavailability study in rats compared with that of BST suspension (SUS). RESULTS: An in vitro cytotoxicity study was done by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide assay method through ATCC cell lines; the percent inhibition was more in SLN when compared with SUS. The pharmacokinetics of BST-SLNs after oral administration in male Wistar rats was studied. The bioavailability of BST was increased by 2.28 fold when compared with that of a BST SUS. CONCLUSION: The results are indicative of SLNs as suitable lipid-based carrier system for improving the oral bioavailability of BST.


Assuntos
Compostos de Anilina , Lipídeos , Nanopartículas , Nitrilas , Quinolinas , Animais , Ratos , Quinolinas/farmacocinética , Quinolinas/administração & dosagem , Nitrilas/farmacocinética , Nitrilas/administração & dosagem , Nitrilas/química , Nanopartículas/química , Compostos de Anilina/farmacocinética , Compostos de Anilina/química , Compostos de Anilina/administração & dosagem , Masculino , Lipídeos/química , Lipídeos/farmacocinética , Disponibilidade Biológica , Portadores de Fármacos/química , Portadores de Fármacos/farmacocinética , Humanos , Ratos Wistar , Sistemas de Liberação de Medicamentos , Lipossomos
17.
Bioorg Med Chem Lett ; 113: 129979, 2024 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-39341398

RESUMO

Lymphocyte activation gene 3 (LAG-3) is an inhibitory immune checkpoint crucial for suppressing the immune response against cancer. Blocking LAG-3 interactions enables T cells to recover their cytotoxic capabilities and diminishes the immunosuppressive effects of regulatory T cells. A cyclic peptide (Cys-Val-Pro-Met-Thr-Tyr-Arg-Ala-Cys, disulfide bridge: 1-9) was recently reported as a LAG-3 inhibitor. Based on this peptide, we designed 19 derivatives by substituting tyrosine residue to maximize LAG-3 inhibition. Screening via TR-FRET assay identified 8 outperforming derivatives, with cyclic peptides 12 [Tyr6(L-3-CN-Phe)], 13 [Tyr6(L-4-NH2-Phe)], and 17 [Tyr6(L-3,5-DiF-Phe)] as top candidates. Cyclic peptide 12 exhibited the highest inhibition (IC50 = 4.45 ± 1.36 µM). MST analysis showed cyclic peptides 12 and 13 bound LAG-3 with KD values of 2.66 ± 2.06 µM and 1.81 ± 1.42 µM, respectively, surpassing the original peptide (9.94 ± 4.13 µM). Docking simulations revealed that cyclic peptide 12 exhibited significantly enhanced binding, with a docking score of -7.236 kcal/mol, outperforming the original peptide (-5.236 kcal/mol) and cyclic peptide 5 (L-4-CN-Phe) (-5.131 kcal/mol). A per-residue decomposition of the interaction energy indicated that the 3-cyano group in cyclic peptide 12 contributes to a more favorable conformation, yielding an interaction energy of -9.22 kcal/mol with Phe443 of MHC-II, compared to -6.03 kcal/mol and -5.619 kcal/mol for cyclic peptides 0 and 5, respectively. Despite promising in vitro results, cyclic peptide 12 failed to inhibit tumor growth in vivo, underscoring the importance of dual immunotherapies targeting several immune checkpoints to achieve anti-tumor efficacy.


Assuntos
Desenho de Fármacos , Imunoterapia , Proteína do Gene 3 de Ativação de Linfócitos , Peptídeos Cíclicos , Animais , Humanos , Camundongos , Antígenos CD/metabolismo , Antígenos CD/química , Antígenos CD/imunologia , Antineoplásicos/química , Antineoplásicos/farmacologia , Antineoplásicos/síntese química , Relação Dose-Resposta a Droga , Estrutura Molecular , Neoplasias/tratamento farmacológico , Neoplasias/imunologia , Peptídeos Cíclicos/química , Peptídeos Cíclicos/farmacologia , Peptídeos Cíclicos/síntese química , Relação Estrutura-Atividade , Nitrilas/química , Nitrilas/metabolismo
18.
Molecules ; 29(18)2024 Sep 12.
Artigo em Inglês | MEDLINE | ID: mdl-39339328

RESUMO

Vertically ordered mesoporous silica films (VMSF) are a class of porous materials composed of ultrasmall pores and ultrathin perpendicular nanochannels, which are attractive in the areas of electroanalytical sensors and molecular separation. However, VMSF easily falls off from the carbonaceous electrodes and thereby impacts their broad applications. Herein, carbon nitride nanosheets (CNNS) were served as an adhesive layer for stable growth of VMSF on the glassy carbon electrode (GCE). CNNS bearing plentiful oxygen-containing groups can covalently bind with silanol groups of VMSF, effectively promoting the stability of VMSF on the GCE surface. Benefiting from numerous open nanopores of VMSF, modification of VMSF's external surface with carbohydrate antigen 15-3 (CA15-3)-specific antibody allows the target-controlled transport of electrochemical probes through the internal silica nanochannels, yielding sensitive quantitative detection of CA15-3 with a broad detection range of 1 mU/mL to 1000 U/mL and a low limit of detection of 0.47 mU/mL. Furthermore, the proposed VMSF/CNNS/GCE immunosensor is capable of highly selective and accurate determination of CA15-3 in spiked serum samples, which offers a simple and effective electrochemical strategy for detection of various practical biomarkers in complicated biological specimens.


Assuntos
Técnicas Biossensoriais , Carbono , Técnicas Eletroquímicas , Eletrodos , Mucina-1 , Nanoestruturas , Nitrilas , Dióxido de Silício , Dióxido de Silício/química , Técnicas Biossensoriais/métodos , Carbono/química , Porosidade , Humanos , Nanoestruturas/química , Técnicas Eletroquímicas/métodos , Mucina-1/sangue , Nitrilas/química , Imunoensaio/métodos , Limite de Detecção
19.
Int J Pharm ; 665: 124684, 2024 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-39270763

RESUMO

Anastrazole (ASZ) is an effective aromatase inhibitor that is used for breast cancer treatment. Nevertheless, ASZ's effectiveness is diminished due to its low water solubility, unregulated release, absence of targeting, and inadequate patient compliance. The goal of the research was to create a hydrogel formulation of ASZ-loaded invasomes (ALI) to enhance the solubility, permeability, targeting, and efficacy of ASZ while also sustaining its release for treatment of breast cancer. The optimized ALI formulation was determined to be 3%w/v phospholipid, 0.15%w/v cholesterol, 3%v/v ethanol, and 1 %v/v cineole based on the results of the pre-formulation study. After conducting in vitro characterization of the optimum formulation, it was combined with carbopol for in vivo examination of its anti-tumor efficacy in a rat model of 7, 12-dimethylbenzanthracene. Compared to free ASZ, ALI hydrogel increased its penetration by 10.67 times and prolonged its release by 64.02%. Compared to the control positive group, ALI hydrogel reduced tumor volume by 99.19% and mortality by 10.93%. The anti-tumor effect of the ALI hydrogel was demonstrated by its ability to accumulate more ASZ in tumors and reduce hypercellular tumors. Overall, transdermal ALI hydrogel shows potential as a promising approach for treating breast cancer.


Assuntos
Anastrozol , Neoplasias da Mama , Hidrogéis , Animais , Feminino , Hidrogéis/química , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/patologia , Anastrozol/administração & dosagem , Humanos , Ratos , 9,10-Dimetil-1,2-benzantraceno , Solubilidade , Liberação Controlada de Fármacos , Nitrilas/química , Linhagem Celular Tumoral , Triazóis/química , Triazóis/administração & dosagem , Triazóis/farmacocinética , Triazóis/farmacologia , Células MCF-7 , Inibidores da Aromatase/administração & dosagem , Inibidores da Aromatase/química , Inibidores da Aromatase/farmacologia , Inibidores da Aromatase/farmacocinética , Sistemas de Liberação de Medicamentos/métodos
20.
ACS Appl Mater Interfaces ; 16(40): 54520-54528, 2024 Oct 09.
Artigo em Inglês | MEDLINE | ID: mdl-39340431

RESUMO

Wearable electronics have significantly advanced the development of highly stretchable strain sensors, which are essential for applications such as health monitoring, human-machine interfaces, and energy harvesting. Fiber-based sensors and polymeric materials are promising due to their flexibility and tunable properties, although balancing sensitivity and stretchability remains a challenge. This study introduces a novel composite strain sensor that combines poly(3-hexylthiophene) and tetrafluoro-tetracyanoquinodimethane to form a charge-transfer complex (CTC) with carbon nanotubes (CNTs) on a styrene-butadiene-styrene substrate. The CTC improves conductivity through effective charge transfer, while CNTs provide mechanical reinforcement and maintain conductive paths, preventing cracks under large strains. Purposefully introduced wrinkles in the structure enhance the detection of small strains. The sensor demonstrated a broad strain-sensing range from 0.01 to 200%, exhibiting high sensitivity to both minor and major deformations. Mechanical tests confirmed strong stress-strain performance, and electrical tests indicated significant conductivity improvements with CNT integration. These results highlight the potential of the sensor for applications in health monitoring, human-machine interfaces, and energy harvesting, effectively mimicking the tactile sensing abilities of human skin.


Assuntos
Nanotubos de Carbono , Dispositivos Eletrônicos Vestíveis , Nanotubos de Carbono/química , Humanos , Condutividade Elétrica , Tiofenos/química , Nitrilas/química
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