Enzyme-armed nanocleaner provides superior detoxification against organophosphorus compounds via a dual-action mechanism.

By inhibiting acetylcholinesterase (AChE) activity, organophosphate compounds (OPs) can quickly cause severe injury to the nervous system and death, making it extremely difficult to rescue victims after OP exposure. However, it is quite challenging to construct scavengers that neutralize and eliminate these harmful chemical agents promptly in the blood circulation system. Herein, we report an enzyme-armed biomimetic nanoparticle that enables a 'targeted binding and catalytic degradation' action mechanism designed for highly efficient in vivo detoxification (denoted as 'Nanocleaner'). Specifically, the resulting Nanocleaner is fabricated with polymeric cores camouflaged with a modified red blood cell membrane (RBC membrane) that is inserted with the organophosphorus hydrolase (OPH) enzyme. In such a subtle construct, Nanocleaner inherits abundant acetylcholinesterase (AChE) on the surface of the RBC membrane, which can specifically lure and neutralize OPs through biological binding. The OPH enzyme on the membrane surface breaks down toxicants catalytically. The in vitro protective effects of Nanocleaner against methyl paraoxon (MPO)-induced inhibition of AChE activity were validated using both preincubation and competitive regimens. Furthermore, we selected the PC12 neuroendocrine cell line as an experimental model and confirmed the cytoprotective effects of Nanocleaner against MPO. In mice challenged with a lethal dose of MPO, Nanocleaner significantly reduces clinical signs of intoxication, rescues AChE activity and promotes the survival rate of mice challenged with lethal MPO. Overall, these results suggest considerable promise of enzyme-armed Nanocleaner for the highly efficient removal of OPs for clinical treatment.

Molecular interaction mechanisms on (-)-epigallocatechin-3-gallate improving activities of inhibited acetylcholinesterase by selected organophosphorus pesticides in vitro & vivo.

(-)-Epigallocatechin-3-gallate (EGCG) is reported to have benefits for the treatment of Alzheimer's disease by binding with acetylcholinesterase (AChE) to enhance the cholinergic neurotransmission. Organophosphorus pesticides (OPs) inhibited AChE and damaged the nervous system. This study investigated the combined effects of EGCG and OPs on AChE activities in vitro & vivo. The results indicated that EGCG significantly reversed the inhibition of AChE caused by OPs. In vitro, EGCG reactived AChE in three group tubes incubated for 110 min, and in vivo, it increased the relative activities of AChE from less than 20% to over 70% in brain and vertebral of zebrafish during the exposure of 34 h. The study also proposed the molecular interaction mechanisms through the reactive kinetics and computational analyses of density functional theory, molecular docking, and dynamic modeling. These analyses suggested that EGCG occupied the key residues, preventing OPs from binding to the catalytic center of AChE, and interfering with the initial affinity of OPs to the central active site. Hydrogen bonding, conjugation, and steric interactions were identified as playing important roles in the molecular interactions. The work suggests that EGCG antagonized the inhibitions of OPs on AChE activities and potentially offered the neuroprotection against the induced damage.

Alcohol-based hydrophobic deep eutectic solvents and ultrasound-assisted liquid phase microextraction followed by GC-MS for the extraction and analysis of organophosphorus pesticides in the blood of farmers.

Organophosphorus pesticides (OPPs) are a group of pesticides that are most widely used in the agricultural sector, and farmers are exposed to these chemicals more than other members of society. In this work, an environmentally friendly, simple, and safe ultrasound-assisted dispersive liquid-liquid microextraction (USA-DLLME) method using alcohol-based hydrophobic deep eutectic solvents (HDESs) followed by gas chromatography-mass spectroscopy (GC-MS) was developed for the extraction and determination of OPPs in the blood of farmers studied in Ravansar cohort. DESs synthesized from thymol as hydrogen bond donor (HBD) and aliphatic alcohols as hydrogen bond acceptor (HBA) have been used as extractants. Under optimal experimental conditions, the reproducibility of the method based on 7 replicate measurements of 10 µg L-1 of OPPs in blood samples was in the range of 1.4-3.8%. The method showed a linearity in the range of 0.01-150 µg L-1. The limits of detection and limits of quantification were between 0.003 and 0.02 µg L-1 and 0.01-0.05 µg L-1, respectively. The matrix effect and accuracy of the method were confirmed by spiking different amounts of OPPs in real blood samples and obtaining relative recoveries in the range of 91-112%. The results showed that the concentration of OPPs in the case group was significantly higher than in the control group, which is because the case group was exposed to OPPs during the spraying of agricultural products.

Characterization of the N5-dimethylallyl-FMN Intermediate in the Biosynthesis of Prenylated-FMN Catalyzed by UbiX.

Prenylated-FMN (prFMN) is the cofactor used by the UbiD-like family of decarboxylases that catalyzes the decarboxylation of various aromatic and unsaturated carboxylic acids. prFMN is synthesized from reduced FMN and dimethylallyl phosphate (DMAP) by a specialized prenyl transferase, UbiX. UbiX catalyzes the sequential formation of two bonds, the first between N5 of the flavin and C1 of DMAP, and the second between C6 of the flavin and C3 of DMAP. We have examined the reaction of UbiX with both FMN and riboflavin. Although UbiX converts FMN to prFMN, we show that significant amounts of the N5-dimethylallyl-FMN intermediate are released from the enzyme during catalysis. With riboflavin as the substrate, UbiX catalyzes only a partial reaction, resulting in only N5-dimethylallyl-riboflavin being formed. Purification of the N5-dimethylallyl-FMN adduct allowed its structure to be verified by 1H NMR spectroscopy and its reactivity to be investigated. Surprisingly, whereas reduced prFMN oxidizes in seconds to form the stable prFMN semiquinone radical when exposed to air, N5-dimethylallyl-FMN oxidizes much more slowly over several hours; in this case, oxidation is accompanied by spontaneous hydrolysis to regenerate FMN. These studies highlight the important contribution that cyclization of the prenyl-derived ring of prFMN makes to the cofactor's biological activity.

Reduced graphene oxide decorated NiCo2(OH)6 nanoflowers for vortexed assisted dispersive µ-solid-phase extraction of organophosphorus pesticides in baby food cereal, rice and wheat flour.

Food safety is an important issue to protect humane health and improve the life quality. Hence, analysis of the possible contaminants in food samples is essential. A rapid and efficient vortexed-assisted dispersive µ-solid-phase extraction coupled with gas chromatography-mass spectrometry was proposed for simultaneous separation/preconcentration and determination of five commonly used organophosphorus pesticides. Reduced graphene oxide decorated NiCo2(OH)6 nanoflowers as a novel nanostructure was synthetized and introduced for separation of the target pesticides from the wheat flour, rice flour, and baby food cereal samples. The characterization of the nanoflowers was accomplished by SEM-EDX, XRD, and FT-IR techniques. The main factors including pH, the amount of nanoflower, the volume of sample solution, salt concentration (ionic strength), desorption conditions (i.e. desorption solvent type and volume, and desorption time) on the pesticides extraction efficiencies were inquired using matrixed match method. Applying the optimum conditions, the linearity of 0.100-500.000 µg kg-1, LODs and LOQs in the range of 0.03-0.04 µg kg-1 and 0.1 µg kg-1 for the studied food samples were obtained. The repeatability (intra-day precision (n = 5)) of ≤ 2.0 % and reproducibility (inter-day precision, days = 5, n = 3) of ≤3.1 % and were appraise at three concentration levels (10, 50 and 100 µg kg-1 of each analyte). High relative recoveries of 90.0-99.3 % ascertained high potential of the presented method for complex matrix analysis.

Oncogenic and telomeric G-quadruplexes: Targets for porphyrin-triphenylphosphonium conjugates.

DNA chains with sequential guanine (G) repeats can lead to the formation of G-quadruplexes (G4), which are found in functional DNA and RNA regions like telomeres and oncogene promoters. The development of molecules with adequate structural features to selectively stabilize G4 structures can counteract cell immortality, highly described for cancer cells, and also downregulate transcription events underlying cell apoptosis and/or senescence processes. We describe here, the efficiency of four highly charged porphyrins-phosphonium conjugates to act as G4 stabilizing agents. The spectrophotometric results allowed to select the conjugates P2-PPh3 and P3-PPh3 as the most promising ones to stabilize selectively G4 structures. Molecular dynamics simulation experiments were performed and support the preferential binding of P2-PPh3 namely to MYC and of P3-PPh3 to KRAS. The ability of both ligands to block the activity of Taq polymerase was confirmed and also their higher cytotoxicity against the two melanoma cell lines A375 and SK-MEL-28 than to immortalized skin keratinocytes. Both ligands present efficient cellular uptake, nuclear co-localization and high ability to generate 1O2 namely when interacting with G4 structure. The obtained data points the synthesized porphyrins as promising ligands to be used in a dual approach that can combine G4 stabilization and Photodynamic therapy (PDT).

Chemistry of installing epitranscriptomic 5-modified cytidines in RNA oligomers.

Studies of 5-hydroxymethylcytidine (hm5C), 5-formylcytidine (f5C) and 5-carboxycytidine (ca5C) modifications as products of the 5-methylcytidine (m5C) oxidative demethylation pathway in cellular mRNAs constitute an important element of the new epitranscriptomic field of research. The dynamic process of m5C conversion and final turnover to the parent cytidine is considered a post-transcriptional layer of gene-expression regulation. However, the regulatory mechanism associated with epitranscriptomic cytidine modifications remains largely unknown. Therefore, oligonucleotides containing m5C oxidation products are of great value for the next generation of biochemical, biophysical, and structural studies on their function, metabolism, and contribution to human diseases. Herein, we summarize the synthetic strategies developed for the incorporation of hm5C, f5C and ca5C into RNA oligomers by phosphoramidite chemistry, including post-synthetic C5-cytidine functionalization and enzymatic methods.

Mitochondria-targeting nanozyme for catalytical therapy and radiotherapy with activation of cGAS-STING.

BACKGROUND: Overcoming radio-resistance and enhance radio-sensitivity to obtain desired therapeutic outcome plays an important role in treating cancer. METHODS: Here we constructed a versatile enzyme-like nano-radiosensitizer MDP. MDP is composed of MnCO decorated and Ru-based nanozyme with triphenylphosphine (TPP) group coordinated on the surface. RESULTS: Due to the mitochondria-targeting ability of TPP and enhanced permeability and retention effect (EPR) effect of MDP, MDP accumulated in the mitochondria of tumor cells. Therefore, quantities of reactive oxygen species were produced via multiple enzyme-like properties including peroxidase (POD) and catalase (CAT) in a tumor microenvironment mimicking status. In additional, more energy of radiation ionizing was deposed in tumor site via Compton effect and secondary electron scattering by Ru element. Impressively, it was disclosed that the nanozyme can act as a cGAS-STING agonist to provoke immune response of the system, which hereby further elevated this combined therapy. CONCLUSIONS: Collectively, we fabricated a novel nanozyme with POD and CAT mimicking properties for the combination therapy of catalytical therapy, radiotherapy as well as immune therapy to eliminate cancer.

Photocatalytic degradation of organophosphorus flame retardants in aqueous solutions: a review and future prospects.

The widespread use of organophosphorus flame retardants (OPFRs) in industrial and household products increases the risk of their environmental exposure, posing a serious threat to ecosystems and human health. Photocatalytic technology has been widely used in wastewater treatment due to its high efficiency, mild reaction conditions, and robustness. This review summarizes the current status of research on photocatalytic degradation of OPFRs, focusing on the effect of different types of catalysts on the degradation efficiency, the effects of pH, and co-existing inorganic and organic ions. And pH and co-existing inorganic mainly affect the active oxygen and the active surface sites of the catalyst. In addition, toxicological calculations of the intermediates of the degradation pathway using T.E.S.T. and ECOSAR showed that photocatalysis could effectively reduce the toxicity of OPFRs. Development of new photocatalytic materials, in-depth study of the degradation mechanism of different catalysts and flame retardants, and attention to practical applications and toxicity issues can be the development direction of future research.

Quaternary phosphonium AIEgens nanoparticles as innovative agents for developing latent fingerprints.

Quaternary phosphonium salts, a significant category of organophosphorus compounds, have garnered substantial attention from chemists due to their wide range of applications across various research areas. These compounds are utilized in organic synthesis, catalysis, medicinal chemistry, natural materials, and coordination chemistry. Their versatility and effectiveness in these fields make them valuable tools in scientific research. Despite their extensive use in various applications, the potential of quaternary phosphonium compounds as fluorescent agents for revealing latent fingerprints (LFPs) remains largely unexplored, presenting an exciting opportunity for further research and development in forensic science. In this study, we designed molecules that combine the aggregation-induced emission (AIE) chromophore with triphenylphosphine to create a series of novel AIE amphiphiles, namely TPP1, TPP2, and TPP3. Through precise adjustment of the carbon chain length between the phenoxy group and the terminal triphenylphosphine, we were able to finely tune the nanostructures and hydrophobicity of the materials. TPP3 emerged as the optimal candidate, possessing the ideal particle size and hydrophobicity to effectively bind to LFPs, thus enabling efficient fingerprint visualization with enhanced fluorescence upon aggregation. Our findings introduce an innovative approach to fingerprint visualization, offering high selectivity, superior imaging of level 3 structures, and long-term effectiveness (up to 30 days). Additionally, TPP3's outstanding performance in imaging level 3 structures of LFPs is beneficial for analyzing incomplete LFPs and identifying individuals. By significantly improving the detection and analysis of LFPs, this approach ensures more accurate and reliable identification, making it invaluable for forensic investigations and security measures. The adaptability of these compounds to various fingerprint surfaces highlights their potential in diverse practical applications, enhancing their utility in both forensic science and security fields. This versatility allows for precise fingerprint visualization across different scenarios, making them a critical tool for advancing biometric and security technologies.

Puerarin-Loaded Liposomes Co-Modified by Ischemic Myocardium-Targeting Peptide and Triphenylphosphonium Cations Ameliorate Myocardial Ischemia-Reperfusion Injury.

Purpose: Mitochondrial damage may lead to uncontrolled oxidative stress and massive apoptosis, and thus plays a pivotal role in the pathological processes of myocardial ischemia-reperfusion (I/R) injury. However, it is difficult for the drugs such as puerarin (PUE) to reach the mitochondrial lesion due to lack of targeting ability, which seriously affects the expected efficacy of drug therapy for myocardial I/R injury. Methods: We prepared triphenylphosphonium (TPP) cations and ischemic myocardium-targeting peptide (IMTP) co-modified puerarin-loaded liposomes (PUE@T/I-L), which effectively deliver the drug to mitochondria and improve the effectiveness of PUE in reducing myocardial I/R injury. Results: In vitro test results showed that PUE@T/I-L had sustained release and excellent hemocompatibility. Fluorescence test results showed that TPP cations and IMTP double-modified liposomes (T/I-L) enhanced the intracellular uptake, escaped lysosomal capture and promoted drug targeting into the mitochondria. Notably, PUE@T/I-L inhibited the opening of the mitochondrial permeability transition pore, reduced intracellular reactive oxygen species (ROS) levels and increased superoxide dismutase (SOD) levels, thereby decreasing the percentage of Hoechst-positive cells and improving the survival of hypoxia-reoxygenated (H/R)-injured H9c2 cells. In a mouse myocardial I/R injury model, PUE@T/I-L showed a significant myocardial protective effect against myocardial I/R injury by protecting mitochondrial integrity, reducing myocardial apoptosis and decreasing infarct size. Conclusion: This drug delivery system exhibited excellent mitochondrial targeting and reduction of myocardial apoptosis, which endowed it with good potential extension value in the precise treatment of myocardial I/R injury.

Metadynamics Study of Lipid-Mediated Antibacterial Toxin Binding to the EmrE Multiefflux Protein.

EmrE is a bacterial efflux protein in the small multidrug-resistant (SMR) family present in Escherichia coli. Due to its small size, 110 residues in each dimer subunit, it is an ideal model system to study ligand-protein-membrane interactions. Here in our work, we have calculated the free energy landscape of benzyltrimetylammonium (BTMA) and tetraphenyl phosphonium (TPP) binding to EmrE using the enhanced sampling method-multiple walker metadynamics. We estimate that the free energy of BTMA binding to EmrE is -21.2 ± 3.3 kJ/mol and for TPP is -43.6 ± 3.8 kJ/mol. BTMA passes through two metastable states to reach the binding pocket, while TPP has a more complex binding landscape with four metastable states and one main binding site. Our simulations show that the ligands interact with the membrane lipids at a distance 1 nm away from the binding site which forms a broad local minimum, consistent for both BTMA and TPP. This site can be an alternate entry point for ligands to partition from the membrane into the protein, especially for bulky and/or branched ligands. We also observed the membrane lipid and C-terminal 110HisA form salt-bridge interactions with the helix-1 residue 22LysB. Our free energy estimates and clusters are in close agreement with experimental data and give us an atomistic view of the ligand-protein-lipid interactions. Understanding the binding pathway of these ligands can guide us in future design of ligands that can alter or halt the function of EmrE.

On resin synthesis of phosphoethanolamine cellulose.

Phosphoethanoamine (pEtN) cellulose is a chemically modified cellulose present in some bacterial biofilms. To deepen our understanding of this biopolymer and its biological function, access to chemically defined pEtN-cellulose oligosaccharides is desirable. Herein, we report an on resin protocol for the fast synthesis of tailor-made pEtN-celluloses. The cellulose backbone is prepared by automated glycan assembly and then specifically functionalized with pEtN groups, allowing for access to a collection of ten pEtN-cellulose oligomers with different amount and pattern of pEtN.

Synthesis and comparative analysis of the cytotoxicity and mitochondrial effects of triphenylphosphonium and F16 maslinic and corosolic acid hybrid derivatives.

The cytotoxic profile and antiproliferative and mitochondrial effects of triterpene acid conjugates with mitochondriotropic lipophilic triphenylphosphonium (TPP+) and F16 cations were evaluated. Maslinic and corosolic acids chosen as the investigation objects were synthesized from commercially available oleanolic and ursolic acids. Study of the cytotoxic activity of TPP+ and F16 triterpenoid derivatives against six tumor cell lines demonstrated a comparable synergistic effect in the anticancer activity, which was most pronounced in the case of MCF-7 mammary adenocarcinoma cells and Jurkat and THP-1 leukemia cells. The corosolic and maslinic acid hybrid derivatives caused changes in the progression of tumor cell cycle phases when present in much lower doses than their natural triterpene acid precursors. The treatment of tumor cell lines with the conjugates resulted in the cell cycle arrest in the G1 phase and increase in the cell population in the subG1 phase. The cationic derivatives of the acids were markedly superior to their precursors as inducers of hyperproduction of reactive oxygen species and more effectively decreased the mitochondrial potential in isolated rat liver mitochondria. We concluded that the observed cytotoxic effect of TPP+ and F16 triterpenoid conjugates is attributable to the ability of these compounds to initiate mitochondrial dysfunctions. Their cytotoxicity, antiproliferative action, and mitochondrial effects depend little on the type of cationic groups used.

Tripeptide linked dispiro cyclotriphosphazene conjugates: Synthesis, molecular docking analysis of compounds binding within cancer cell line receptors and in vitro cytotoxic and genotoxic activities.

The novel dioxybiphenyl bridged-cyclotriphosphazenes (DPP) bearing tripeptide were synthesized and investigated for their molecular docking analysis, visualizing their binding profiles within various cancer cell line receptors and in vitro cytotoxic and genotoxic properties. The dipeptide compound (Tyr-Phe) was treated with various amino acids to obtain the tripeptide compounds (Tyr-Phe-Gly, Tyr-Phe-Ala, Tyr-Phe-Val, Tyr-Phe-Phe, and Tyr-Phe-Leu). These synthesized tripeptides were subsequently treated with DPP to obtain novel phosphazene compounds bearing tripeptide structures. As a result, the synthesis of target molecules with phosphazene compound in the center and biphenyl and tripeptide groups in the side arms was obtained for the first time in this study. Examining the cytotoxic studies in vitro of our newly synthesized compounds demonstrated the anticancer properties against four selected human cancer cell lines, including breast (MCF-7), ovarian (A2780), prostate (PC-3), and colon (Caco-2) cancer cells. The Comet Assay analysis determined that the cell death mechanism of most of the compounds with cytotoxic activity stemmed from the DNA damage mechanism. Among the compounds, the DPP-Tyr-Phe-Phe compound seems to have the best anticancer activity against the subjected cell lines (Except for A2780) with IC50 values equal to 20.18, 72.14, 12.21, and 5.17 µM against breast, ovarian, prostate, and colon cancer cell lines, respectively. For this reason, the molecular docking analysis was conducted for the DTPP compound to visualize its binding geometry and profile within the target enzyme's binding site associated with the specific cancer cell line. The analysis revealed that the DTPP derivative exhibited an optimal binding conformation and characteristics within the target enzyme's binding site, aligning well with the experimental data. Based on the data, these compounds are believed to be strong candidate molecules for both pharmaceutical and clinical applications.

α-Selective Solid-Phase Synthesis of Glycosyl Phosphate Repeating Structure Via the Phosphoramidite Method.

Lipophosphoglycans (LPGs) are found on the surface of Leishmania, a protozoan parasite, and are immunologically important. Herein, disaccharide 1-phosphate repeating units of LPGs were successfully synthesized on a solid support with high anomeric purity using a disaccharide α-1-phosphoramidite building block. To enhance solubility in the reaction solvent, hydroxy-protecting groups in the form of para-t-butylbenzoyl were introduced to the building block. The saccharide chain was elongated via stable glycosyl boranophosphate linkages, followed by the conversion of inter-sugar linkages to phosphodiester counterparts using an oxaziridine derivative. The addition of a silylating reagent post-reaction with the oxaziridine derivative efficiently facilitated the conversion of boranophosohodiesters to phosphodiesters. This method enabled the α-selective synthesis of up to 15 repeating units, marking the longest homogeneous repeating units of LPGs synthesized chemically. Given the chain length equivalence to native LPGs, the method developed herein holds promise for advancing anti-Leishmanial pharmaceuticals and vaccines.

Near-infrared fluorescent probe for ultrasensitive detection of organophosphorus pesticides and visualization of their interaction with butyrylcholinesterase in living cells.

The toxicity of organophosphorus pesticides (OPs) can catastrophically cause liver cell damage and inhibit the catalytic activity of cholinesterase. We designed and synthesized a near-infrared fluorescent probe HP-LZB with large Stokes shift which can specifically identify and detect butyrylcholinesterase (BChE) and visually explore the interaction between OPs and endogenous BChE in living cells. Fluorescence was turned on when HP-LZB was hydrolyzed into HP-LZ in the presence of BChE, and OPs could inhibit BChE's activity resulting in a decrease of fluorescence. Six OPs including three oxon pesticides (paraoxon, chlorpyrifos oxon and diazoxon) and their corresponding thion pesticides (parathion, chlorpyrifos and diazinon) were investigated. Both in vitro and cell experiments indicated that only oxon pesticides could inhibit BChE's activity. The limits of detection (LODs) of paraoxon, chlorpyrifos oxon and diazoxon were as low as 0.295, 0.007 and 0.011 ng mL-1 respectively and the recovery of OPs residue in vegetable samples was satisfactory. Thion pesticides themselves could hardly inhibit the activity of BChE and are only toxic when they are converted to their corresponding oxon form in the metabolic process. However, in this work, thion pesticides were found not be oxidized into their oxon forms in living HepG2 cells due to the lack of cytochrome P450 in hepatoma HepG2 cell lines. Therefore, this probe has great application potential in effectively monitoring OPs in real plant samples and visually exploring the interaction between OPs and BChE in living cells.

Triphenylphosphonium-modified catiomers enhance in vivo mRNA delivery through stabilized polyion complexation.

Nanocarriers based on cationic materials play a central role in the success of mRNA-based therapies. Traditionally, amine-bearing lipids and polymers have been successfully employed for creating mRNA-loaded nanocarriers, though they still present challenges, such as physical and biological instability, limiting both delivery efficiency and therapeutic potential. Non-amine cations could be a promising avenue in addressing these limitations. However, such alternatives remain notably underexplored. Herein, we introduced triphenylphosphonium (TPP) as an alternative cationic moiety for mRNA delivery, leveraging its advantageous properties for nucleic acid complexation. Through the modification of amine-bearing catiomers, we replaced traditional amine-based counterparts with TPP to create innovative polymeric micelles as mRNA nanocarriers. A comprehensive analysis, encompassing physicochemical, thermodynamic, and computational approaches, revealed that the TPP substitution significantly influenced polymer self-assembly, mRNA binding, and the overall stability of mRNA-loaded polymeric micelles. Upon intravenous injection, TPP-bearing micelles demonstrated a remarkable increase in mRNA bioavailability, facilitating efficient protein production in solid tumors. These findings provide a compelling rationale for substituting amines with TPP, emphasizing their potential for advancing mRNA therapeutics.

Can Porphyrin-Triphenylphosphonium Conjugates Enhance the Photosensitizer Performance Toward Bacterial Strains?

Antimicrobial photodynamic treatment (aPDT) offers an alternative option for combating microbial pathogens, and in this way, addressing the challenges of growing antimicrobial resistance. In this promising and effective approach, cationic porphyrins and related macrocycles have emerged as leading photosensitizers (PS) for aPDT. In general, their preparation occurs via N-alkylation of nitrogen-based moieties with alkyl halides, which limits the ability to fine-tune the features of porphyrin-based PS. Herein, is reported that the conjugation of porphyrin macrocycles with triphenylphosphonium units created a series of effective cationic porphyrin-based PS for aPDT. The presence of positive charges at both the porphyrin macrocycle and triphenylphosphonium moieties significantly enhances the photodynamic activity of porphyrin-based PS against both Gram-positive and Gram-negative bacterial strains. Moreover, bacterial photoinactivation is achieved with a notable reduction in irradiation time, exceeding 50%, compared to 5,10,15,20-tetrakis(1-methylpyridinium-4-yl)porphyrin (TMPyP), used as the reference and known as good PS. The improved capability of the porphyrin macrocycle to generate singlet oxygen combined with the enhanced membrane interaction promoted by the presence of triphenylphosphonium moieties represents a promising approach to developing porphyrin-based PS with enhanced photosensitizing activity.

Highly sensitive turn-on electrochemical sensing of organophosphorus pesticides by integration of homogeneous reaction and heterogeneous catalytic signal amplification.

Enzyme-inhibited electrochemical sensor is a promising strategy for detecting organophosphorus pesticides (OPs). However, the poor stability of enzymes and the high oxidation potential of thiocholine signal probe limit their potential applications. To address this issue, an indirect strategy was proposed for highly sensitive and reliable detection of chlorpyrifos by integrating homogeneous reaction and heterogeneous catalysis. In the homogeneous reaction, Hg2+ with low oxidation potential was employed as signal probe for chlorpyrifos detection since its electroactivity can be inhibited by thiocholine, which was the hydrolysate of acetylthiocholine catalyzed by acetylcholinesterase. Additionally, Co,N-doped hollow porous carbon nanocage@carbon nanotubes (Co,N-HPNC@CNT) derived from ZIF-8@ZIF-67 was utilized as high-performance electrode material to amplify the stripping voltammetry signal of Hg2+. Thanks to their synergistic effect, the sensor exhibited outstanding sensing performance, excellent stability and good anti-interference ability. This strategy paves the way for the development of high-performance OP sensors and their application in food safety.