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1.
Mikrochim Acta ; 191(7): 368, 2024 06 04.
Article in English | MEDLINE | ID: mdl-38833176

ABSTRACT

A colorimetric analysis platform has been successfully developed based on FeCo-NC dual-atom nanozyme (FeCo-NC DAzyme) for the detection of organophosphorus pesticides (OPPs). The FeCo-NC DAzyme exhibited exceptional oxidase-like activity (OXD), enabling the catalysis of colorless TMB to form blue oxidized TMB (oxTMB) without the need for H2O2 involvement. By combining acid phosphatase (ACP) hydrolase with FeCo-NC DAzyme, a "FeCo-NC DAzyme + TMB + ACP + SAP" colorimetric system was constructed, which facilitated the rapid detection of malathion. The chromogenic system was applied to detect malathion using a smartphone-based app and an auxiliary imaging interferogram device for colorimetric measurements, which have a linear range of 0.05-4.0 µM and a limit of detection (LOD) as low as 15 nM in real samples, comparable to UV-Vis and HPLC-DAD detection methods. Overall, these findings present a novel approach for convenient, rapid, and on-site monitoring of OPPs.


Subject(s)
Colorimetry , Limit of Detection , Pesticides , Smartphone , Colorimetry/methods , Pesticides/analysis , Organophosphorus Compounds/analysis , Organophosphorus Compounds/chemistry , Malathion/analysis , Malathion/chemistry , Oxidoreductases/chemistry , Iron/chemistry , Acid Phosphatase/analysis , Acid Phosphatase/chemistry , Benzidines
2.
Spectrochim Acta A Mol Biomol Spectrosc ; 317: 124434, 2024 Sep 05.
Article in English | MEDLINE | ID: mdl-38735113

ABSTRACT

Probing intracellular organelles with fluorescent dyes offers opportunities to understand the structures and functions of these cellular compartments, which is attracting increasing interests. Normally, the design principle varies for different organelle targets as they possess distinct structural and functional profiles against each other. Therefore, developing a probe with dual intracellular targets is of great challenge. In this work, a new sort of donor-π-bridge-acceptor (D-π-A) type coumaranone dyes (CMO-1/2/3/4) have been prepared. Four fluorescent probes (TPP@CMO-1/2/3/4) were then synthesized by linking these coumaranone dyes with an amphiphilic cation triphenylphosphonium (TPP). Interestingly, both TPP@CMO-1 and TPP@CMO-2 exhibited dual color emission upon targeting to two different organelles, respectively. The green emission is well localized in mitochondria, while, the red emission realizes nucleoli imaging. RNA is the target of TPP@CMOs, which was confirmed by spectroscopic analysis and computational calculation. More importantly, the number and morphology changes of nucleoli under drug stress have been successfully evaluated using TPP@CMO-1.


Subject(s)
Cell Nucleolus , Fluorescent Dyes , Mitochondria , Organophosphorus Compounds , Organophosphorus Compounds/chemistry , Mitochondria/metabolism , Mitochondria/drug effects , Fluorescent Dyes/chemistry , Fluorescent Dyes/chemical synthesis , Humans , Cell Nucleolus/metabolism , HeLa Cells , Spectrometry, Fluorescence , Color
3.
Anal Bioanal Chem ; 416(15): 3569-3584, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38698257

ABSTRACT

Protein adducts are important biological targets for traceability of organophosphorus nerve agents (OPNAs). Currently, the recognized biomarkers that can be used in actual samples in the field of chemical forensics only include Y411 in albumin and the active nonapeptide in butyrylcholinesterase (BChE). To explore stable and reliable protein adducts and increase the accuracy of OPNAs traceability further, we gradually expanded OPNAs-albumin adducts based on single and group adduct collection. Several stable peptides were found via LC-MS/MS analysis in human serum albumin (HSA) exposed to OPNAs in a large exposure range. These adducts were present in HSA samples exposed to OPNAs of each concentration, which provided data support for the reliability and stability of using adducts to trace OPNAs. Meanwhile, the formation mechanism of OPNAs-cysteine adduct was clarified via computer simulations. Then, these active sites found and modified peptides were used as raw materials for progressive expansion of albumin adducts. We constructed an OPNAs-HSA adducts group, in which a specific agent is the exposure source, and three or more active peptides constitute data sets for OPNAs traceability. Compared with single or scattered protein adducts, the OPNAs-HSA adduct group improves OPNAs identification by mutual verification using active peptides or by narrowing the identity range of the exposure source. We also determined the minimum detectable concentration of OPNAs for the adduct group. Two or more peptides can be detected when there is an exposure of 50 times the molar excess of OPNAs in relation to HSA. This improved the accuracy of OPNAs exposure and identity confirmation. A collection of OPNAs-albumin adducts was also examined. The collection was established by collecting, classifying, and integrating the existing albumin adducts according to the species to which each albumin belongs, the types of agents, and protease. This method can serve as a reference for discovering new albumin adducts, characteristic phosphonylated peptides, and potential biomarkers. In addition, to avoid a false negative for OPNAs traceability using albumin adducts, we explored OPNAs-cholinesterase adducts because cholinesterase is more reactive with OPNAs than albumin. Seven active peptides in red blood cell acetylcholinesterase (RBC AChE) and serum BChE can assist in OPNAs exposure and identity confirmation.


Subject(s)
Nerve Agents , Organophosphorus Compounds , Serum Albumin, Human , Tandem Mass Spectrometry , Humans , Nerve Agents/chemistry , Nerve Agents/analysis , Organophosphorus Compounds/chemistry , Tandem Mass Spectrometry/methods , Serum Albumin, Human/chemistry , Chromatography, Liquid/methods , Biomarkers/blood , Peptides/chemistry
4.
ACS Appl Mater Interfaces ; 16(22): 28991-29002, 2024 Jun 05.
Article in English | MEDLINE | ID: mdl-38769310

ABSTRACT

Triphenylphosphine functionalized carbon dots (TPP-CDs) showcase robust mitochondria targeting capacity owing to their positive electrical properties. However, TPP-CDs typically involve complicated synthesis steps and time-consuming postmodification procedures. Especially, the one-step target-oriented synthesis of TPP-CDs and the regulation of TPP linkage modes remain challenges. Herein, we propose a free-radical-initiated random copolymerization in combination with hydrothermal carbonation to regulate the TPP backbone linkage for target-oriented synthesis of triphenylphosphine copolymerization carbon dots (TPPcopoly-CDs). The linkage mechanism of random copolymerization reactions is directional, straightforward, and controllable. The TPP content and IC50 of hydroxyl radicals scavenging ability of TPPcopoly-CDs are 53 wt % and 0.52 mg/mL, respectively. TPP serves as a charge control agent to elevate the negatively charged CDs by 20 mV. TPPcopoly-CDs with negative charge can target mitochondria, and in the corresponding mechanism the TPP moiety plays a crucial role in targeting mitochondria. This discovery provides a new perspective on the controlled synthesis, TPP linkage modes, and mitochondrial targeting design of TPP-CDs.


Subject(s)
Carbon , Mitochondria , Organophosphorus Compounds , Quantum Dots , Organophosphorus Compounds/chemistry , Carbon/chemistry , Mitochondria/metabolism , Mitochondria/drug effects , Quantum Dots/chemistry , Humans , Reactive Oxygen Species/metabolism , Free Radical Scavengers/chemistry , Free Radical Scavengers/chemical synthesis , Free Radical Scavengers/pharmacology , HeLa Cells
5.
Article in English | MEDLINE | ID: mdl-38735125

ABSTRACT

Protein adducts are vital targets for exploring organophosphorus nerve agents (OPNAs) exposure and identification, that can be used to characterize the chemical burden and initiate chemical safety measures. However, the use of protein adducts as biomarkers of OPNA exposure has developed slowly. To further promote the development of biomarkers in chemical forensics, it is crucial to expand the range of modified peptides and active sites, and describe the characteristics of OPNA adducts at specific reaction sites. This study utilized multi-species and multi-source albumins as the protein targets. We identified 56 peptides in albumins from various species (including human, horse, rat and pig), that were modified by at least two OPNAs. Diverse modification characteristics were observed in response to certain agents: including (1) multiple sites on the same peptide modified by one or more agents, (2) different reactivities at the same site in homologous albumins, and (3) different preferences at the same active sites associated with differences in the biological matrix during exposure. Our studies provided an empirical reference with rationalized underpinnings supported by estimated conformation energetics through molecular modeling. We employed different peptide markers for detection of protein adducts, as (one would do) in forensic screening for identification and quantification of chemical damage. Three characteristic peptides were screened and analyzed in human albumin, including Y287ICENQDSISSK, K438VPQVS443TPTLVEVSR, and Y162LY164EIAR. Stable fragment ions with neutral loss were found from their tandem MS/MS spectra, which were used as characteristic ions for identification and extraction of modified peptides in enzymatic digestion mixtures. Coupling these observations with computer simulations, we found that the structural stability of albumin and albumin-adduct complexes (as well as the effective force that promotes stability of different adducts) changes in the interval before and after adduct formation. In pig albumin, five active peptides existed stably in vivo and in vitro. Most of them can be detected within 30 min after OPNA exposure, and the detection window can persist about half a month. These early findings provided the foundation and rationale for utilizing pig albumin as a sampling target for rapid analysis in future forensic work.


Subject(s)
Nerve Agents , Organophosphorus Compounds , Animals , Humans , Rats , Organophosphorus Compounds/chemistry , Swine , Nerve Agents/chemistry , Nerve Agents/analysis , Horses , Tandem Mass Spectrometry/methods , Peptides/chemistry , Peptides/analysis , Albumins/chemistry , Albumins/metabolism , Biomarkers/analysis , Biomarkers/chemistry
6.
Eur J Med Chem ; 272: 116478, 2024 Jun 05.
Article in English | MEDLINE | ID: mdl-38718624

ABSTRACT

Metallodrugs exhibiting distinct mechanisms of action compared with cisplatin hold promise for overcoming cisplatin resistance and improving the efficacy of anticancer drugs. In this study, a new series of rhodium (Rh)(III) complexes containing tris(triphenylphosphine)rhodium(I) chloride [(TPP)3RhCl] (TPP = triphenylphosphine, TPP=O = triphenylphosphine oxide) and 8-hydroxyquinoline derivatives (H-XR1-H-XR4), namely [Rh(XR1)2(TPP)Cl]·(TPP=O) (Yulin Normal University-1a [YNU-1a]), [Rh(XR2)2(TPP)Cl] (YNU-1b), [Rh(XR3)2(TPP)Cl] (YNU-1c), and [Rh(XR4)2(TPP)Cl] (YNU-1d), was synthesized and characterized via X-ray diffraction, mass spectrometry and IR. The cytotoxicity of the compounds YNU-1a-YNU-1d in Hep-G2 and HCC1806 human cancer cell lines and normal HL-7702 cell line was evaluated. YNU-1c exhibited cytotoxicity and selectivity in HCC1806 cells (IC50 = 0.13 ± 0.06 µM, selectivity factor (SF) = 384.6). The compounds YNU-1b and YNU-1c, which were selected for mechanistic studies, induced the activation of apoptotic pathways and mitophagy. In addition, these compounds released cytochrome c, cleaved caspase-3/pro-caspase-3 and downregulated the levels of mitochondrial respiratory chain complexes I/IV (M1 and M4) and ATP. The compound YNU-1c, which was selected for in vivo experiments, exhibited tumor growth inhibition (58.9 %). Importantly, hematoxylin and eosin staining and TUNEL revealed that HCC1806 tumor tissues exhibited significant apoptotic characteristics. YNU-1a-YNU-1d compounds are promising drug candidates that can be used to overcome cisplatin resistance.


Subject(s)
Antineoplastic Agents , Cell Proliferation , Coordination Complexes , Drug Screening Assays, Antitumor , Mitophagy , Oxyquinoline , Rhodium , Humans , Antineoplastic Agents/pharmacology , Antineoplastic Agents/chemistry , Antineoplastic Agents/chemical synthesis , Rhodium/chemistry , Rhodium/pharmacology , Oxyquinoline/chemistry , Oxyquinoline/pharmacology , Oxyquinoline/chemical synthesis , Coordination Complexes/pharmacology , Coordination Complexes/chemistry , Coordination Complexes/chemical synthesis , Animals , Structure-Activity Relationship , Cell Proliferation/drug effects , Mitophagy/drug effects , Molecular Structure , Organophosphorus Compounds/pharmacology , Organophosphorus Compounds/chemistry , Organophosphorus Compounds/chemical synthesis , Dose-Response Relationship, Drug , Apoptosis/drug effects , Mice , Cell Line, Tumor
7.
J Inorg Biochem ; 257: 112585, 2024 Aug.
Article in English | MEDLINE | ID: mdl-38718498

ABSTRACT

Ruthenium complexes are one of the most promising anticancer drugs and ferroptosis is a novel form of regulated cell death, the study on the effect of Ru complexes on ferroptosis is helpful to find more effective antitumor drugs. Here, the synthesis and characterization of two Ru complexes containing 8-hydroxylquinoline and triphenylphosphine as ligands, [Ru(L1) (PPh3)2Cl2] (Ru-1), [Ru(L2) (PPh3)2Cl2] (Ru-2), were reported. Complexes Ru-1 âˆ¼ Ru-2 showed good anticancer activity in Hep-G2 cells. Researches indicated that complexes Ru-1 âˆ¼ Ru-2 could be enriched and appear as red fluorescence in the mitochondria, arouse dysfunction of mitochondria, induce the accumulation of reactive oxygen species (ROS) and lipid peroxidation (LPO), while the morphology of nuclei and cell apoptosis had no significant change. Further experiments proved that GPX4 and Ferritin were down-regulated, which eventually triggered ferroptosis in Hep-G2 cells. Remarkably, Ru-1 showed high inhibitory activity against xenograft tumor growth in vivo (TGIR = 49%). This study shows that the complex Ru-1 could act as a novel drug candidate by triggering cell ferroptosis.


Subject(s)
Antineoplastic Agents , Coordination Complexes , Ferroptosis , Mitochondria , Ruthenium , Ferroptosis/drug effects , Humans , Antineoplastic Agents/pharmacology , Antineoplastic Agents/chemistry , Antineoplastic Agents/chemical synthesis , Animals , Ruthenium/chemistry , Coordination Complexes/pharmacology , Coordination Complexes/chemistry , Coordination Complexes/chemical synthesis , Mitochondria/drug effects , Mitochondria/metabolism , Mice , Hep G2 Cells , Reactive Oxygen Species/metabolism , Organophosphorus Compounds/chemistry , Organophosphorus Compounds/pharmacology , Mice, Nude , Xenograft Model Antitumor Assays , Oxyquinoline/chemistry , Oxyquinoline/pharmacology , Lipid Peroxidation/drug effects , Mice, Inbred BALB C
8.
Mikrochim Acta ; 191(6): 319, 2024 05 10.
Article in English | MEDLINE | ID: mdl-38727763

ABSTRACT

The high-residual and bioaccumulation property of organophosphorus pesticides (OPs) creates enormous risks towards the ecological environment and human health, promoting the research for smart adsorbents and detection methods. Herein, 2D hemin-bridged MOF nanozyme (2D-ZHM) was fabricated and applied to the efficient removal and ultrasensitive dual-mode aptasensing of OPs. On the one hand, the prepared 2D-ZHM contained Zr-OH groups with high affinity for phosphate groups, endowing it with selective recognition and high adsorption capacity for OPs (285.7 mg g-1 for glyphosate). On the other hand, the enhanced peroxidase-mimicking biocatalytic property of 2D-ZHM allowed rapid H2O2-directed transformation of 3,3',5,5'-tetramethylbenzidine to oxidic product, producing detectable colorimetric or photothermal signals. Using aptamers of specific recognition capacity, the rapid quantification of two typical OPs, glyphosate and omethoate, was realized with remarkable sensitivity and selectivity. The limit of detections (LODs) of glyphosate were 0.004 nM and 0.02 nM for colorimetric and photothermal methods, respectively, and the LODs of omethoate were 0.005 nM and 0.04 nM for colorimetric and photothermal methods, respectively. The constructed dual-mode aptasensing platform exhibited outstanding performance for monitoring OPs in water and fruit samples. This work provides a novel pathway to develop MOF-based artificial peroxidase and integrated platform for pollutant removal and multi-mode aptasensing.


Subject(s)
Glycine , Glyphosate , Hemin , Limit of Detection , Metal-Organic Frameworks , Pesticides , Pesticides/analysis , Pesticides/chemistry , Metal-Organic Frameworks/chemistry , Hemin/chemistry , Glycine/analogs & derivatives , Glycine/chemistry , Glycine/analysis , Colorimetry/methods , Benzidines/chemistry , Adsorption , Water Pollutants, Chemical/analysis , Water Pollutants, Chemical/chemistry , Hydrogen Peroxide/chemistry , Dimethoate/analysis , Dimethoate/chemistry , Aptamers, Nucleotide/chemistry , Organophosphorus Compounds/analysis , Organophosphorus Compounds/chemistry
9.
Nanoscale ; 16(20): 9827-9835, 2024 May 23.
Article in English | MEDLINE | ID: mdl-38695525

ABSTRACT

Green-fluorescent biocompatible carbon dots with a quantum yield of 40% were successfully synthesized through a solvothermal process and then they are comprehensively characterized. The carbon dots showed a negatively charged surface owing to the presence of carboxylic groups. This negative surface charge hinders the effective targeting and imaging of mitochondria. To address this limitation, a new approach is developed in this study. An amphiphile containing phenylalanine, with a positively charged polar head consisting of triphenylphosphine and a hydrophobic aliphatic tail, was designed, synthesized, purified, and characterized. This amphiphile formed spherical micelle-type nanostructures in an aqueous medium in the aggregated state. Although these nanoprobes lack inherent fluorescence, they exhibited the capability to image mitochondria when their spherical micelle-type nanostructures were decorated with negatively charged fluorescent nanocarbon dots in both cancerous (KB cells) and non-cancerous (CHO cells) cell lines. Notably, carbon dots without the amphiphile failed to penetrate the cell membrane as they exhibited significantly low emission inside the cell. This study extensively explored the cell entry mechanism of the hybrid nanoprobes. The photophysical changes and the interaction between the negatively charged carbon dots and the positively charged nanospheres of the amphiphile were also analyzed in this study.


Subject(s)
Carbon , Mitochondria , Quantum Dots , Carbon/chemistry , Mitochondria/metabolism , Humans , Quantum Dots/chemistry , Animals , CHO Cells , Cricetulus , Micelles , Phenylalanine/chemistry , Phenylalanine/analogs & derivatives , Fluorescent Dyes/chemistry , Hydrophobic and Hydrophilic Interactions , Surface-Active Agents/chemistry , Amino Acids/chemistry , Organophosphorus Compounds/chemistry , Cell Line, Tumor
10.
Food Chem ; 448: 139144, 2024 Aug 01.
Article in English | MEDLINE | ID: mdl-38579559

ABSTRACT

Tris(2,4-di-tert-butylphenyl) phosphite (AO168), an organophosphite antioxidant, can be oxidized to tris(2,4-di-tert-butylphenyl) phosphate (AO168 = O) during the production, processing, and application of plastics. AO168 = O can be further transformed to bis(2,4-di-tert-butylphenyl) phosphate and 2,4-di-tert-butylphenol. Here, we discovered the contamination of AO168 and its transformation products in dairy products for the first time. More samples contained AO168 (mean concentration: 8.78 ng/g wet weight [ww]), bis(2,4-di-tert-butylphenyl) phosphate (mean:11.1 ng/g ww) and 2,4-di-tert-butylphenol (mean: 46.8 ng/g ww) than AO168 = O (mean: 40.2 ng/g ww). The concentrations of AO168 and its transformation products were significantly correlated, and differed with the packaging material and storage conditions of the product. Estimated daily intakes (EDIs) of AO168 and its transformation products were calculated. Although the overall dietary risks were below one, transformation products accounted for 96.7% of the total hazard quotients. The high-exposure EDIs of total AO168 were above the threshold of toxicological concern (300 ng/kg bw/day), and deserve continual monitoring.


Subject(s)
Dairy Products , Food Contamination , Phosphites , Food Contamination/analysis , Humans , Phosphites/analysis , Phosphites/chemistry , Dairy Products/analysis , Dietary Exposure/analysis , Animals , Food Packaging/instrumentation , Organophosphorus Compounds/analysis , Organophosphorus Compounds/chemistry
11.
Talanta ; 275: 126065, 2024 Aug 01.
Article in English | MEDLINE | ID: mdl-38663061

ABSTRACT

In practical applications, the rapid and efficient detection of universal organophosphorus pesticides (OPs) can assist inspectors in quickly identifying the presence of OPs in samples. However, this presents a challenge for most well-established methods, typically designed to detect only a specific type of organophosphorus molecule at a time. In this proof-of-concept study, we draw inspiration from the structural similarities among OPs to develop innovative peptide-based fluorescence probes for the first time, which could efficiently detect a broad range of OPs within a mere 3 min. Analysis of fluorescence curve fitting reveals a clear linear correlation between the fluorescent intensity of the peptide probes and the concentration of OPs. Additionally, the selectivity analysis indicates that these peptide fluorescent probes exhibit an excellent response to various OPs while maintaining sufficient selectivity for detecting other pesticide types. Accurate sample analysis has also highlighted the potential of these peptide probes as practical tools for the rapid detection of OPs in actual vegetable samples. In summary, this proof-of-concept study presents an innovative approach to designing and developing ultrafast, universally peptide-based OP probes. These custom-designed peptide probes may facilitate rapid sample screening and offer initial quantification for OPs, potentially saving valuable time and effort in practical OP detection.


Subject(s)
Fluorescent Dyes , Organophosphorus Compounds , Peptides , Pesticides , Fluorescent Dyes/chemistry , Pesticides/analysis , Peptides/chemistry , Organophosphorus Compounds/analysis , Organophosphorus Compounds/chemistry , Spectrometry, Fluorescence/methods , Vegetables/chemistry
12.
J Inorg Biochem ; 256: 112570, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38685138

ABSTRACT

This work reports on the synthesis of triphenylphosphine-labelled cationic phthalocyanines (Pc) complexed with bovine serum albumin (BSA) and gold nanoparticles (Au NPs). This nano-complex (Pc-BSA-Au) is studied for its photodynamic therapy (PDT) activity compared to the non-complexed Pc counterpart. The photochemical properties and in vitro PDT efficacies of the Pc and the nano-complex were determined and are compared herein. The singlet oxygen (1O2) yields of the Pcs were determined and are reported in DMF. A singlet oxygen quantum yield of 0.47 was obtained for the Pcs. The PDT efficacies of the complexes were thereafter determined using malignant melanoma A375 cancer cell line in vitro. An increase in the cell toxicity was observed for cells treated with Pc-BSA-Au compared to those treated with the Pc alone. The cell survival percentages were 23.1% for cells treated with Pc-BSA-Au and 48.7% for those treated with Pc alone under PDT treatments.


Subject(s)
Gold , Indoles , Isoindoles , Melanoma , Metal Nanoparticles , Organophosphorus Compounds , Photochemotherapy , Photosensitizing Agents , Serum Albumin, Bovine , Gold/chemistry , Gold/pharmacology , Serum Albumin, Bovine/chemistry , Humans , Metal Nanoparticles/chemistry , Photochemotherapy/methods , Indoles/chemistry , Indoles/pharmacology , Cell Line, Tumor , Organophosphorus Compounds/chemistry , Organophosphorus Compounds/pharmacology , Melanoma/drug therapy , Melanoma/pathology , Photosensitizing Agents/pharmacology , Photosensitizing Agents/chemistry , Photosensitizing Agents/chemical synthesis , Animals , Antineoplastic Agents/pharmacology , Antineoplastic Agents/chemistry , Cell Survival/drug effects , Cattle , Singlet Oxygen/metabolism
13.
Spectrochim Acta A Mol Biomol Spectrosc ; 316: 124336, 2024 Aug 05.
Article in English | MEDLINE | ID: mdl-38678838

ABSTRACT

For addressing the challenges of strong affinity SERS substrate to organophosphorus pesticides (OPs), herein, a rapid water-assisted layer-by-layer heteronuclear growth method was investigated to grow uniform UiO-66 shell with controllable thickness outside the magnetic core and provide abundant defect sites for OPs adsorption. By further assembling the tailored Au@Ag, a highly sensitive SERS substrate Fe3O4-COOH@UiO-66/Au@Ag (FCUAA) was synthesized with a SERS enhancement factor of 2.11 × 107. The substrate's suitability for the actual vegetable samples (cowpeas and peppers) was confirmed under both destructive and non-destructive detection conditions, showing a strong SERS response to fenthion and triazophos, with limits of detection of 1.21 × 10-5 and 2.96 × 10-3 mg/kg in the vegetables under destructive conditions, and 0.13 and 1.39 ng/cm2 for non-destructive detection, respectively. The FCUAA substrate had high SERS performance, effective adsorption capability for OPs, and demonstrated good applicability, thus exhibiting great potential for rapid detection of trace OPs residues in the food industry.


Subject(s)
Pesticide Residues , Spectrum Analysis, Raman , Spectrum Analysis, Raman/methods , Pesticide Residues/analysis , Vegetables/chemistry , Gold/chemistry , Organophosphorus Compounds/analysis , Organophosphorus Compounds/chemistry , Silver/chemistry , Fenthion/analysis , Triazoles/chemistry , Triazoles/analysis , Limit of Detection , Organothiophosphates/analysis , Food Contamination/analysis , Adsorption
14.
Biomacromolecules ; 25(5): 2701-2714, 2024 May 13.
Article in English | MEDLINE | ID: mdl-38608139

ABSTRACT

Over decades of development, while phosphoramidite chemistry has been known as the leading method in commercial synthesis of oligonucleotides, it has also revolutionized the fabrication of sequence-defined polymers (SDPs), offering novel functional materials in polymer science and clinical medicine. This review has introduced the evolution of phosphoramidite chemistry, emphasizing its development from the synthesis of oligonucleotides to the creation of universal SDPs, which have unlocked the potential for designing programmable smart biomaterials with applications in diverse areas including data storage, regenerative medicine and drug delivery. The key methodologies, functions, biomedical applications, and future challenges in SDPs, have also been summarized in this review, underscoring the significance of breakthroughs in precisely synthesized materials.


Subject(s)
Biocompatible Materials , Drug Delivery Systems , Oligonucleotides , Organophosphorus Compounds , Polymers , Regenerative Medicine , Regenerative Medicine/methods , Biocompatible Materials/chemistry , Polymers/chemistry , Drug Delivery Systems/methods , Humans , Oligonucleotides/chemistry , Organophosphorus Compounds/chemistry , Animals
15.
Nanoscale ; 16(19): 9462-9475, 2024 May 16.
Article in English | MEDLINE | ID: mdl-38639449

ABSTRACT

The dimerization of boron dipyrromethene (BODIPY) moieties is an appealing molecular design approach for developing heavy-atom-free triplet photosensitizers (PSs). However, BODIPY dimer-based PSs generally lack target specificity, which limits their clinical use for photodynamic therapy. This study reports the synthesis of two mitochondria-targeting triphenylphosphonium (TPP)-functionalized meso-ß directly linked BODIPY dimers (BTPP and BeTPP). Both BODIPY dimers exhibited solvent-polarity-dependent singlet oxygen (1O2) quantum yields, with maximum values of 0.84 and 0.55 for BTPP and BeTPP, respectively, in tetrahydrofuran. The compact orthogonal geometry of the BODIPY dimers facilitated the generation of triplet excited states via photoinduced charge separation (CS) and subsequent spin-orbit charge-transfer intersystem crossing (SOCT-ISC) processes and their rates were dependent on the energetic configuration between the frontier molecular orbitals of the two BODIPY subunits. The as-synthesized compounds were amphiphilic and hence formed stable nanoparticles (∼36 nm in diameter) in aqueous solutions, with a zeta potential of ∼33 mV beneficial for mitochondrial targeting. In vitro experiments with MCF-7 and HeLa cancer cells indicated the effective localization of BTPP and BeTPP within cancer-cell mitochondria. Under light irradiation, BTPP and BeTPP exhibited robust photo-induced therapeutic effects in both cell lines, with half-maximal inhibitory concentration (IC50) values of ∼30 and ∼55 nM, respectively.


Subject(s)
Boron Compounds , Mitochondria , Nanoparticles , Organophosphorus Compounds , Photochemotherapy , Photosensitizing Agents , Singlet Oxygen , Humans , Boron Compounds/chemistry , Boron Compounds/pharmacology , Organophosphorus Compounds/chemistry , Organophosphorus Compounds/pharmacology , Mitochondria/metabolism , Mitochondria/drug effects , Photosensitizing Agents/chemistry , Photosensitizing Agents/pharmacology , Nanoparticles/chemistry , Singlet Oxygen/metabolism , Singlet Oxygen/chemistry , MCF-7 Cells , Cell Survival/drug effects , HeLa Cells , Dimerization
16.
ACS Sens ; 9(5): 2325-2333, 2024 May 24.
Article in English | MEDLINE | ID: mdl-38666660

ABSTRACT

Organophosphorus nerve agents (OPNAs) pose a great threat to humanity. Possessing extreme toxicity, rapid lethality, and an unassuming appearance, these chemical warfare agents must be quickly and selectively identified so that treatment can be administered to those affected. Chromogenic detection is the most convenient form of OPNA detection, but current methods suffer from false positives. Here, nitrogenous base adducts of dirhodium(II,II) acetate were synthesized and used as chromogenic detectors of diethyl chlorophosphate (DCP), an OPNA simulant. UV-vis spectrophotometry was used to evaluate the sensitivity and selectivity of the complexes in the detection of DCP. Visual limits of detection (LOD) for DCP were as low as 1.5 mM DCP, while UV-vis-based LODs were as low as 0.113 µM. The dirhodium(II,II) complexes were also tested with several potential interferents, none of which produced a visual color change that could be mistaken for OPNA response. Ultimately, the Rh2(OAc)4(1,8-diazabicyclo[5.4.0]undec-7-ene)2 complex showed the best combination of detection capability and interferent resistance. These results, when taken together, show that dirhodium(II,II) paddlewheel complexes with nitrogenous base adducts can produce instant, selective, and sensitive detection of DCP. It is our aim to further explore and apply this new motif to produce even more capable OPNA sensors.


Subject(s)
Nerve Agents , Rhodium , Rhodium/chemistry , Nerve Agents/analysis , Nerve Agents/chemistry , Coordination Complexes/chemistry , Organophosphorus Compounds/analysis , Organophosphorus Compounds/chemistry , Limit of Detection , Chromogenic Compounds/chemistry , Chemical Warfare Agents/analysis , Chemical Warfare Agents/chemistry
17.
Drug Discov Today ; 29(6): 103983, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38641237

ABSTRACT

Mitochondria are one of the major sources of energy as well as regulators of cancer cell metabolism. Thus, they are potential targets for the effective treatment and management of cancer. Research has explored triphenylphosphonium (TPP) derivatives as potent cancer-targeting ligands because of their lipophilic nature and mitochondrial affinity. In this review, we summarize the utility of TPP-based conjugates targeting mitochondria in different types of cancer and other diseases, such as neurodegenerative and cardiovascular disorders. Such conjugates offer versatile therapeutic potential by modulating membrane potential, influencing reactive oxygen species (ROS) production, and coupling of molecular modifications (such as ATP metabolism and energy metabolism). Thus, we highlight TPP conjugates as promising mitochondria-targeting agents for use in targeted drug delivery systems.


Subject(s)
Drug Delivery Systems , Mitochondria , Neoplasms , Organophosphorus Compounds , Humans , Ligands , Organophosphorus Compounds/chemistry , Organophosphorus Compounds/pharmacology , Animals , Mitochondria/drug effects , Mitochondria/metabolism , Neoplasms/drug therapy , Antineoplastic Agents/pharmacology , Antineoplastic Agents/chemistry , Reactive Oxygen Species/metabolism
18.
Food Chem ; 451: 139368, 2024 Sep 01.
Article in English | MEDLINE | ID: mdl-38657518

ABSTRACT

A unique strategy for developing porous membrane protected micro-solid phase extraction has been provided. An electrospun composite was fabricated on the sheet of membrane. To this end, NiFe-layered double hydroxide/Nylon 6 composite nanofibers were coated on a polypropylene membrane sheet followed by folding into a pocket shape, which were then utilized as a novel extractive device to extract of organophosphorus pesticides from fresh fruit juice samples prior to liquid chromatography-tandem mass spectrometry (LC-MS/MS) analysis. The fabricated hybrid composites were successfully characterized. The effective parameters on extraction performance were investigated. LODs were 0.020-0.065 ng mL-1. Excellent linearity (R2≥0.996) was observed between 0.05 and 100.0 ng mL-1. RSDs% were in the range of 3.1-5.8% (intra-day, n = 3) and 2.6-5.5% (inter-day, n = 3×3). Satisfactory related recovery values within the acceptable range of 90.7-111.2% with RSDs% below 6.7% were achieved for the analysis of real samples.


Subject(s)
Caprolactam , Fruit and Vegetable Juices , Polymers , Polypropylenes , Solid Phase Microextraction , Tandem Mass Spectrometry , Fruit and Vegetable Juices/analysis , Polypropylenes/chemistry , Solid Phase Microextraction/instrumentation , Solid Phase Microextraction/methods , Polymers/chemistry , Caprolactam/chemistry , Caprolactam/analogs & derivatives , Pesticides/isolation & purification , Pesticides/chemistry , Food Contamination/analysis , Organophosphorus Compounds/isolation & purification , Organophosphorus Compounds/chemistry , Organophosphorus Compounds/analysis , Nickel/chemistry , Nickel/isolation & purification , Porosity , Chromatography, Liquid/instrumentation , Solid Phase Extraction/instrumentation , Solid Phase Extraction/methods
19.
Int J Biol Macromol ; 266(Pt 2): 131276, 2024 May.
Article in English | MEDLINE | ID: mdl-38561117

ABSTRACT

Skin aging, a complex physiological progression marked by collagen degradation, poses substantial challenges in dermatology. Recombinant collagen emerges as a potential option for skin revitalization, yet its application is constrained by difficulties in forming hydrogels. We have for the first time developed a highly bioactive Tetrakis(hydroxymethyl) phosphonium chloride (THPC)-crosslinked recombinant collagen hydrogel implant for aging skin rejuvenation. THPC demonstrated superior crosslinking efficiency compared to traditional agents such as EDC/NHS and BDDE, achieving complete recombinant collagen crosslinking at minimal concentrations and effectively inducing hydrogel formation. THPC's four reactive hydroxymethyl groups facilitate robust crosslinking with triple helical recombinant collagen, producing hydrogels with enhanced mechanical strength, excellent injectability, increased stability, and greater durability. Moreover, the hydrogel exhibited remarkable biocompatibility and bioactivity, significantly promoting the proliferation, adhesion, and migration of human foreskin fibroblast-1. In photoaged mice skin models, the THPC-crosslinked collagen hydrogel implant notably improved dermal density, skin elasticity, and reduced transepidermal water loss, creating a conducive environment for fibroblast activity and healthy collagen regeneration. Additionally, it elevated superoxide dismutase (SOD) activity and displayed substantial anti-calcification properties. The THPC-crosslinked recombinant collagen hydrogel implant presents an innovative methodology in combating skin aging, offering significant promise in dermatology and tissue engineering.


Subject(s)
Collagen , Hydrogels , Rejuvenation , Skin Aging , Hydrogels/chemistry , Animals , Collagen/chemistry , Skin Aging/drug effects , Mice , Humans , Cross-Linking Reagents/chemistry , Recombinant Proteins/pharmacology , Recombinant Proteins/administration & dosage , Recombinant Proteins/chemistry , Fibroblasts/drug effects , Skin/drug effects , Cell Proliferation/drug effects , Biocompatible Materials/chemistry , Biocompatible Materials/pharmacology , Organophosphorus Compounds/chemistry , Organophosphorus Compounds/pharmacology
20.
Redox Biol ; 72: 103142, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38581860

ABSTRACT

Platelets are the critical target for preventing and treating pathological thrombus formation. However, despite current antiplatelet therapy, cardiovascular mortality remains high, and cardiovascular events continue in prescribed patients. In this study, first results were obtained with ortho-carbonyl hydroquinones as antiplatelet agents; we found that linking triphenylphosphonium cation to a bicyclic ortho-carbonyl hydroquinone moiety by a short alkyl chain significantly improved their antiplatelet effect by affecting the mitochondrial functioning. The mechanism of action involves uncoupling OXPHOS, which leads to an increase in mitochondrial ROS production and a decrease in the mitochondrial membrane potential and OCR. This alteration disrupts the energy production by mitochondrial function necessary for the platelet activation process. These effects are responsive to the complete structure of the compounds and not to isolated parts of the compounds tested. The results obtained in this research can be used as the basis for developing new antiplatelet agents that target mitochondria.


Subject(s)
Blood Platelets , Hydroquinones , Membrane Potential, Mitochondrial , Mitochondria , Organophosphorus Compounds , Platelet Aggregation Inhibitors , Reactive Oxygen Species , Mitochondria/metabolism , Mitochondria/drug effects , Humans , Platelet Aggregation Inhibitors/pharmacology , Platelet Aggregation Inhibitors/chemistry , Hydroquinones/pharmacology , Hydroquinones/chemistry , Blood Platelets/metabolism , Blood Platelets/drug effects , Organophosphorus Compounds/pharmacology , Organophosphorus Compounds/chemistry , Membrane Potential, Mitochondrial/drug effects , Reactive Oxygen Species/metabolism , Platelet Aggregation/drug effects , Platelet Activation/drug effects , Oxidative Phosphorylation/drug effects
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