Computational study on the mechanisms of inhibition of SARS-CoV-2 Mpro by aldehyde warheads based on DFT.

SARS-CoV-2 main protease, Mpro, plays a crucial role in the virus replication cycle, making it an important target for antiviral research. In this study, a simplified model obtained through truncation is used to explore the reaction mechanism of aldehyde warhead compounds inhibiting Mpro at the level of density functional theory. According to the calculation results, proton transfer (P_T)-nucleophilic attack (N_A) is the rate-determining step in the entire reaction pathway. The water molecule that plays a catalytic role occupies the oxyanion hole, which is unfavorable for the aldehyde warhead to approach the Cys145 SH. Through a hypothetical study of substituting the main chain NH with methylene, it is further confirmed that the P_T-N_A is a proton transfer-dominated process accompanied by a nucleophilic attack reaction. In this process, the oxyanion hole serves only to stabilize the aldehyde oxygen anion and therefore does not have a significant impact on the activation free energy barrier of the step. Our research results provide a unique perspective for understanding the covalent inhibition reaction of the Mpro active site. This study also offers theoretical guidance for the design of new Mpro covalent inhibitors.

Nitrogen-doped carbon dots with high quantum yield for colorimetric and fluorometric detection of ferric ions and in a fluorescent ink.

Nitrogen-doped carbon dots (N-CDs) with a quantum yield of 41 ± 3% and excellent stability were prepared and are shown to be viable probes for the determination of ferric ions, which is a strong quencher of fluorescence. The absorption peak of the N-CDs is located at 325 nm. The optimal excitation and emission wavelengths of the N-CDs are 340 nm and 430 nm, respectively. The fluorometric response to Fe(III) is linear in the ranges between 1.0 and 21.0 µM and between 0.05 and 30.0 µM, and the limits of detection are 0.28 µM in case of colorimetry and 13.5 nM in case of fluorometry. Quenching by Fe(III) is mainly attributed to a combination of chelation (static quenching) and inner filter effect. The N-CDs also can be used as a new sort of fluorescent ink owing to the strong luminous performance and chemical inertness. Graphic abstract The illustration for synthesis of the N-CDs and its applications for colorimetric and fluorescent detection of Fe3+ and fluorescent ink.

Ultrasensitive Electrochemical Detection of Clostridium perfringens DNA Based Morphology-Dependent DNA Adsorption Properties of CeO2 Nanorods in Dairy Products.

Foodborne pathogens such as Clostridium perfringens can cause diverse illnesses and seriously threaten to human health, yet far less attention has been given to detecting these pathogenic bacteria. Herein, two morphologies of nanoceria were synthesized via adjusting the concentration of NaOH, and CeO2 nanorod has been utilized as sensing material to achieve sensitive and selective detection of C. perfringens DNA sequence due to its strong adsorption ability towards DNA compared to nanoparticle. The DNA probe was tightly immobilized on CeO2/chitosan modified electrode surface via metal coordination, and the DNA surface density was 2.51 × 10−10 mol/cm². Under optimal experimental conditions, the electrochemical impedance biosensor displays favorable selectivity toward target DNA in comparison with base-mismatched and non-complementary DNA. The dynamic linear range of the proposed biosensor for detecting oligonucleotide sequence of Clostridium perfringens was from 1.0 × 10−14 to 1.0 × 10−7 mol/L. The detection limit was 7.06 × 10−15 mol/L. In comparison, differential pulse voltammetry (DPV) method quantified the target DNA with a detection limit of 1.95 × 10−15 mol/L. Moreover, the DNA biosensor could detect C. perfringens extracted DNA in dairy products and provided a potential application in food quality control.

Supramolecular DNA sensor based on the integration of host-guest immobilization strategy and WP5-Ag/PEHA supramolecular aggregates.

Primary liver cancer, mostly hepatocellular carcinoma (HCC) is the most common cause of cancer-related deaths around the world. Hepatitis B virus (HBV) DNA is the dominant factor that influences the progression of HCC. In this work, a novel electrochemical sensor triggered by a sandwich hybridization reaction has been developed for the ultrasensitive detection of HBV DNA. The multi-walled carbon nanotubes (MWCNTs) and hydroxylatopillar [5]arene (HP5) stabilized Au nanoparticles are used to modify the electrode to immobilize Rhodamine B-labeled DNA probes and improve the electron transfer efficiency. A supramolecular aggregate was synthesized based on pentaethylenehexamine (PEHA) induced self-assembly behavior of water-soluble pillar [5]arene (WP5) stabilized Ag nanoparticles through host-guest interaction, which serves as signal materials. The sensitivity of the sensor has enhanced on account of the electrochemical oxidation from Ag to Ag+ to yield an electrochemical response greater than that of the single silver nanoparticle. Linear sweep voltammetry (LSV) curves illustrate that the response has a good linear relationship with the logarithm of HBV-DNA concentration in a wide range from 0.1 fmol/L to 0.1 nmol/L, and the detection limit is 0.19 fmol/L according to the 3σ rule. Besides, the sensor shows good reproducibility, stability and selectivity, providing a promising prospect for application in disease diagnosis and prognosis.

A robust host-guest interaction controlled probe immobilization strategy for the ultrasensitive detection of HBV DNA using hollow HP5-Au/CoS nanobox as biosensing platform.

The combination of supramolecular chemistry and nanotechnology has potentially applied in the construction of biosensors, and thus improves the analytical performance and robustness of electron devices. Herein, a new sandwich-type DNA sensor was constructed for ultrasensitive determination of hepatitis B virus (HBV) DNA, a recognized marker for chronic hepatitis B. The water-soluble pillar[5]arene stabilized Pd NPs combined with reduced graphene oxide nanosheet (WP5-Pd/RGO) was synthesized and employed as supporting material for the modification of electrode surface. The probe DNA was immobilized onto the electrode surface through a new strategy based on the host-guest interaction between WP5 and methylene blue labeled DNA (MB-DNA). Moreover, MOF-derived cobalt sulfide nanobox was prepared to anchor the hydroxylatopillar[5]arene stabilized Au NPs (HP5-Au/CoS), which had superior electrocatalytic performance towards H2O2 reduction to achieve signal amplification. Under the optimized conditions, the proposed sensor displayed a linear relationship between amperometric currents and the logarithm of tDNA solution from 1 × 10-15 mol/L to 1 × 10-9 mol/L, and a low detection limit of 0.32 fmol/L. What's more, the DNA sensor had remarkable behaviors of stability, reproducibility, specificity, and accuracy, which provided a potential and promising prospect for clinical diagnosis and analysis.

Facile and clean synthesis of dihydroxylatopillar[5]arene-stabilized gold nanoparticles integrated Pd/MnO2 nanocomposites for robust and ultrasensitive detection of cardiac troponin I.

In this work, a novel, facile, clean synthesis of monodisperse Au nanoparticles (AuNPs) with an average diameter of 5 nm was achieved by reducing HAuCl4 with dihydroxylatopillar[5]arene (2HP5) in basic solution without the use of harsh reagents and/or external energy. Accordingly, toluidine blue (TB), one electrochemcial indicator, could enter into the cavity of 2HP5 to fabricate host-guest complex through strong electrostatic interaction and charge-transfer interaction, which significantly enhanced the loading quantity of TB and effectively suppressed the leaking of TB resulting in an ultrasensitive and robust electrochemical response. More importantly, the integration of 2HP5-stabilized AuNPs and Pd-decorated MnO2 nanocomposites (2HP5@Au-Pd/MnO2) might usually obtain a novel functional-enhanced materials and lead to new properties and improving the analytical performance and robustness of electrochemical devices. Therefore, we construct a sandwich-type electrochemical immunosensor using TB-2HP5@Au-Pd/MnO2 nanocomposites as the transducing materials for robust and ultrasensitive detection of cardiac troponin I (cTnI), a significant biomarker of acute myocardial infarction. As anticipated, this immunosensor had remarkable robustness, sensitivity, stability, specificity, and corresponded linearly to the concentration of cTnI over a wide range from 0.005 to 20 ng mL-1 with a low detection limit of 2 pg mL-1 (S/N = 3). The proposed electrochemical immunosensor showed acceptable recoveries in human serum, indicating that macrocycle-stabilized metal nanoparticle might be a promising emerging transducer material for the detection of biological markers.

Water-soluble pillar[6]arene functionalized PdPt porous core-shell octahedral nanodendrites to construct highly sensitive and robust neuron-specific enolase immunosensor by host-guest chemistry assisted catalytic amplification.

In this work, water-soluble pillar[6]arene functionalized PdPt porous core-shell octahedral nanodendrites (WP6@PdPt PCONs) were simply synthesized and used for the fabrication of NSE immunosensor. The newest generation of macrocyclic host and biomimetic nano-enzymes have been effectively integrated to achieve the robust immobilization of signal molecules by host-guest molecular recognition and sensitively catalytic amplification of electrochemical signals. The addition of Pd and the formation of WP6@PdPt PCONs unique bimetallic nanostructure are beneficial to changing Pt-based catalyst electronic structure, accelerating the electron transport, promoting the generation of synergistic catalysis effect. Compared with enzyme-based methods, the fabricated sandwich-type immunosensor demonstrates more advantages in robustness owing to the introduction of host-guest chemistry and biomimetic nano-enzymes. In the wide range from 0.0003 to 100.00 ng mL-1, a good linear relationship (R2 = 0.998) and a low LOD (0.095 pg mL-1, S/N = 3) can be obtained. The proposed immunosensor shows remarkable analytical performances in the measurements of selectivity, stability, reproducibility, and real sample analysis, which provided a promising approach for clinical detection of NSE in human serum. Besides, the successful synthesis of WP6@PdPt PCONs provides a new idea for the preparation of biosensors based on bionic materials, nanotechnology and host-guest molecule recognition.