Template Molecule Research Articles

Lateral flow chromatography strip system for rapid fluorescence determination of phycocyanin in water samples

Phycocyanin (PC) is of great significance to biomedicine and water environmental safety. Hence, it is indispensable to develop facile and rapid method for PC determination. In this investigation, a system containing lateral flow chromatography (LFC) strip (which was deposited with molecularly imprinted polymer (MIP) capped CdTe quantum dots (QDs) based mesoporous structured coated silica nanoparticles, SiO2@QDs@ms-MIP NPs) and miniaturized fluorimeter was first fabricated. In detail, a two-step strategy was utilized for preparation of SiO2@QDs@ms-MIP NPs, which consisted of modification of CdTe QDs onto the silica NPs first, and synthesis of mesoporous imprinting shell by using PC as template molecule and cetyltrimethylammonium bromide (CTAB) as surfactant. After that, novel fluorescence NPs possessing specific recognition and sensitivity toward PC in seawater and lake water were acquired. The resulting fluorescent sensing system exhibited outstanding performances, which included excellent sensitivity (4.5 nmol/L), satisfactory specificity (imprinting factor, 2.31), appropriate linearity range (0.01~5 μmol/L), good recovery (96.0~101.7%), excellent stability (relative standard deviation, RSD<1.1%), wonderful reproducibility (RSD<1.1%), and excellent anti-interference ability. The results of the fluorescent sensing system were superior to those of the commonly used ultraviolet (UV) method. The proposed strategy showed great potential for fast (<10min) and convenient fluorescence detection of PC in real samples.

Rapid screening of Salmonella typhimurium based on a bacterial surface-imprinted polymer-functionalized bipolar electrode-electrochemiluminescence platform

A bipolar electrode-electrochemiluminescence (BPE-ECL) sensor, utilizing a polydopamine (PDA) bacterial surface-imprinted polymer (SIP), has been developed for the detection of Salmonella typhimurium (S. typhimurium). To fabricate this sensor, dopamine (DA) served as the monomer, while S. typhimurium played a crucial role as the template molecule. Through a precision-tuned electropolymerization process, a polymer film template was seamlessly crafted on the cathode of BPE, encasing the target bacteria within its matrix. Once the template was delicately removed, a molecular surface-imprinted film emerged on the cathode, forming a PDA SIP capture probe that was remarkably adept at recognizing and binding to the target bacteria. When the target bacteria was present on the cathode, the Fc-aptamer-S. typhimurium acted as a signal probe to specifically recognized S. typhimurium. Applying a constant potential to the BPE, the oxidation product Fc+, generated at the cathode, accelerating the luminescence of the [Ru(bpy)3]2+/TPrA system on the anode. The sensor exhibited a remarkable sensitivity, capable of detecting S. typhimurium concentrations ranging from 101 to 106 CFU mL−1, with a detection limit of 10 CFU mL−1.

Investigation of the modification of gold electrodes by electrochemical molecularly imprinted polymers as a selective layer for the trace level electroanalysis of PAH

Electrochemical molecularly imprinted polymers (e-MIPs) were grafted for the first time as a thin layer to the surface of a gold electrode to perform trace level electroanalysis of benzo(a)pyrene (BaP). This was achieved by controlled/living radical photopolymerization of a redox tracer monomer (ferrocenylmethyl methacrylate, FcMMA) with ethylene glycol dimethacrylate in the presence of benzo(a)pyrene as the template molecule. For that purpose, a novel photoiniferter-derived SAM was first deposited on the gold surface. The SAM formation was monitored by cyclic voltammetry and electrochemical impedance spectroscopy. Then, the “grafting from” of the e-MIP was achieved upon photoirradiation during a controlled time. Differential pulse voltammetry was used to quantify BaP in aqueous solution by following the modification of the signal of FcMMA. A limit of detection of 0.19 nM in water and a linear range of 0.66 nM to 4.30 nM, were determined, thus validating the enhancement of sensitivity induced by the close contact between the e-MIP and the electrode, and the improved transfer electron.

Electrochemical paper-based sensor based on molecular imprinted polymer and nitrogen-doped graphene for tetracycline determination

In this work, an electrochemical paper-based analytical device (ePAD) based on molecular-imprinted polymer (MIP) and nitrogen-doped graphene (NG) was developed for sensitive electrochemical detection of tetracycline in wastewater. The NG was in-situ synthesized on the paper-based screen-printed carbon electrode (pSPCE) by potentiostatic method to improve the conductivity of the sensor. Subsequently, the MIP were electropolymerized on NG using o-phenylenediamine (oPD) as a functional monomer and tetracycline (TC) as template molecule by cyclic voltammetry (CV) to deliver the specific recognition of TC. The electrode modification process was highly controllable, and the detection efficiency was improved. The electrochemical properties of MIP/NG/ePAD were evaluated by CV, differential pulse voltammetry (DPV), and electrochemical impedance spectroscopy (EIS). Under optimized conditions, the fabricated ePAD sensor showed a good linear relationship with TC concentration ranging from 5 × 10−9 to 1 × 10−5 mol/L with a correlation coefficient (R2) of 0.995 and a detection limit of 3.29 × 10−9 mol/L. The ePAD sensor was successfully applied to TC detection in real water samples with satisfied recoveries from 94.0 % to 106.9 %. The low-cost, portable, high specificity, and reliable ePAD sensor proposed here has promising potential for application in point-of-care testing (POCT) in environmental monitoring.

A facile and selective resonance Rayleigh scattering method for trace nitrite using gold nanocluster surface molecularly imprinted polyisopropylacrylamide probe.

A novel gold nanocluster surface molecularly imprinted polyisopropylacrylamide probe (AuNC@MIP) was synthesized for the specific detection of NO2-, using N-isopropylacrylamide (NIPAM) as the functional monomer, gold nanoclusters (AuNC) as the substrate, ethylene glycol dimethacrylate (EGDMA) as the cross-linking agent, and nitrosophenol (NPN) produced from sodium nitrite (NaNO2) and phenol (PN) as the template molecule, N,N-dimethylformamide (DMF) as the solvent, and azobisisobutyronitrile (AIBN) as the initiator. The nanoprobe was characterized using molecular spectroscopy, XPS, TEM, TGA, and zeta potential analysis. The probes revealed a prominent resonance Rayleigh scattering (RRS) peak at 370 nm. Upon addition of NO2-, the RRS intensity at 370 nm decreased due to the RRS energy transfer enhancing. The linear determination range is 0.125-1.50 nmol/L NO2-, with a limit of detection (LOD) of 0.085 nmol/L. The new RRS method was applied to determine NO2- in meat, dairy products, and water samples, with recovery of 96-107% also relative standard deviations (RSDs) of 1.1-8.0%.

Magnetic Molecularly Imprinted Polymer Combined with Solid-Phase Extraction for Purification of Schisandra chinensis Lignans

Molecularly imprinted polymers (MIPs) can specifically recognize template molecules in solution with imprinted cavities. Due to their capacity for scalable production, they can be used to isolate target products from natural products for industrial production in the fields of pharmaceuticals and food. In this study, magnetic single-template molecularly imprinted polymers (St-MIPs) instead of magnetic multi-template molecularly imprinted polymers (Mt-MIPs) were prepared by surface imprinting using Schizandrol A as a template molecule and deep eutectic solvent (DES) as a functional monomer, combined with solid-phase extraction (SPE) for the adsorption and separation of Schizandrol A, Schisantherin A, Schizandrin A, and Schizandrin B from Schisandra chinensis (Turcz.) Baill. (S. chinensis) fruits extracts. The synthesized MIPs were characterized by FT-IR, TEM, SEM, TG, XRD and VSM, and their adsorption properties were also evaluated. MIPs can specifically recognize the template molecules with high reusability. The purity of the total S. chinensis lignans after SPE was 74.05%, among which that of Schizandrol A, Schisantherin A, Schizandrin A, and Schizandrin B was 33.38%, 8.69%, 16.33% and 15.67%, respectively. Moreover, the one-step synthesis of carrier was easy to operate. And St-MIPs reduced the production cost compared with Mt-MIPs. This study provides a new idea for natural product separation by molecular imprinting technology (MIT).

Molecularly imprinted electrochemical sensor based on APTES-functionalized indium tin oxide electrode for the determination of sulfadiazine.

Anelectrochemical sensor was developedfor the sensitive and selective detection of sulfadiazine(SDZ), based on a molecularly imprinted polymer (MIP) film formed on an indium tin oxide (ITO) electrode through a self-assembly process. The SDZ-imprinted ITO electrode (SDZ-MIP/APTES-ITO) was prepared through in situ polymerization using sulfadiazine, methacrylic acid (MAA), ethylene glycol dimethacrylate (EGDMA), and 2,2'-azobisisobutyronitrile (AIBN) as the template, functional monomer, cross-linker, and initiator respectively. Before polymerization, the ITO electrode was functionalized with 3-aminopropyltriethoxysilane (APTES) to promote covalent attachment of the polymer to the electrode. After polymerization, the template molecule SDZ was removed to create selective recognition sites, forming the molecularly imprinted polymer electrode (MIP/APTES-ITO), which facilitates sulfadiazine detection. The sensor's performance was evaluated using cyclic and differential pulse voltammetry, demonstrating a linear response in the sulfadiazine concentration range 0.1 to 300μM, with a detection limit of 0.11μM. The MIP-based sensor exhibited goodreproducibility, repeatability, selectivity, and stability in sulfadiazine detection. Its practical applicability was confirmed by the successful quantification of sulfadiazine in spiked milk samples.

Detection of the antipsychotic drug cariprazine using a low-cost MIP-based electrochemical sensor and its electrooxidation behaviour

Cariprazine (CAR), a member of the class of atypical antipsychotics, is a widely utilized pharmaceutical agent. Therefore, analytical techniques for its detection in real samples must be established, both for the purposes of treatment and for the advancement of the pharmaceutical industry. In recent years, there have been notable advancements in the development of sensor-based technologies, particularly those employing electrochemical detection for the rapid and precise analysis of a range of pharmaceuticals. Accordingly, the present study initially examined the voltammetric behaviour of CAR using an unmodified glassy carbon electrode (GCE). The mechanism of electrochemical oxidation was proposed, and subsequently, an electrochemical method for the determination of CAR was applied, which demonstrated a detection limit of 6.4 × 10−7 M (0.64 µM) and a broad linear dynamic range (2.5 × 10−6–5.0 × 10−5 M; 2.5–50.0 µM). Subsequently, a molecularly imprinted recognition system was fabricated via a simple one-step electrochemical polymerization process, using CAR as the template molecule and 3-aminophenylboronic acid as the functional monomer. A systematic optimization of the parameters influencing the sensor response was conducted. Upon identifying the optimal conditions, the MIP/GCE demonstrated a commendable sensitivity (177.25 µA/µM) and a detection limit of 1.27 × 10−14 M (12.7 fM) in a linear range from 1.0 × 10−13 to 2.5 × 10−12 M (0.1–2.5 pM). Subsequently, the sensor was effectively utilized to determine CAR in capsule and commercial serum samples, yielding satisfactory recovery values.

A selective resonance Rayleigh scattering method for determination of iodine by graphene oxide surface molecularly imprinted polyacrylamide probe

A new graphene oxide nanosurface molecularly imprinted polymer (GO@MIP) probe was synthesized by microwave irradiation, using graphene oxide (GO) as the carrier, iodine as the template molecule, acrylamide as the functional monomer, ethylene glycol dimethacrylate (EGDMA) as the crosslinking agent, azodiisobutyronitrile (AIBN) as the initiator, and acetonitrile as the pore forming agent. The nanoprobe recognizes the iodine, and exhibits significant resonance Rayleigh scattering energy transfer (RRS-ET) effect between iodine as the acceptor and the nanoprobe as donor. When iodine concentration was in the linear range of 0.02–0.5 mmol/L, the decreased RRS intensity was linear to the concentration. And it was used for the determination of iodine in water samples and iodate ions in salt samples.

Solvent-free mechanochemical synthesis of Mg-gallic acid complex for the fabrication of high-performance supercapacitor porous carbon

At molecular level, it is challenging to construct a porous carbon from magnesium based template and low cost precursor by a facile route for supercapacitive energy storage, e.g. solvent-free approach because the coordination of magnesium ion with organic ligands usually needs participation of solvent. Herein, a balling milling mediated coordination of magnesium acetate and gallic acid was developed in the absence of solvent to prepare porous carbon. The key of the present strategy lies in the generation of volatile HAc, orienting the reaction in a favorable direction for the formation of complexes. The resultant porous carbon (denoted BGMC) owns a high microporostiy ratio (24.2 % vs template-free derived ones of 11.1 %), open accessed microstructure and hydrophobic character. As electrode for supercapacitor, in aqueous electrolyte, the BGMC based supercapacitor achieves a high energy density of 19.2 Wh kg−1@900 W kg−1, while, in organic electrolyte of 1.0 M TEABF4/AN, the symmetric device based on BGMC delivers energy in a wide voltage window of 0–3.5 V with large energy of 34.4 Wh kg−1@1750 W kg−1, which is superior to those of recently reported carbon based devices. And more, at high current density of 10 A g−1, the BGMC device can resist continual charge/discharge for 30 000 cycles, showing an excellent cycling stability. Our strategy involving solvent-freely coordination of template and precursor molecule to prepare porous carbon open up a route with facile, scalable and easy-operable attributes towards the preparation of functional porous carbon.

Simultaneous Cycloadditions in the Solid State via Supramolecular Assembly

AbstractChemical reactions conducted in the solid phase (specifically, crystalline) are much less numerous than solution reactions, primarily due to reduced motion, flexibility, and reactivity. The main advantage of crystalline‐state transformations is that reactant molecules can be designed to self‐assemble into specific spatial arrangements, often leading to high control over product regiochemistry and/or stereochemistry. In crystalline‐phase transformations, typically only one type of reaction occurs, and a sacrificial template molecule is frequently used to facilitate self‐assembly, similar to a catalyst or enzyme. Here, we demonstrate the first system designed to undergo two chemically unique and orthogonal cycloaddition reactions simultaneously within a single crystalline solid. Well‐controlled supramolecular self‐assembly of two molecules containing different reactive moieties affords orthogonal reactivity without use of a sacrificial template. Using only UV light, the simultaneous [2+2] and [4+4] cycloadditions are achieved regiospecifically, stereospecifically, and products are obtained in high yield, whereas a simultaneous solution‐state reaction affords a mixture of isomers in low yield. Application of dually‐reactive systems toward (supra)molecular solar thermal storage materials is also discussed. This work demonstrates fundamental chemical approaches for orthogonal reactivity in the crystalline state and highlights the complexity and reversibility that can be achieved with supramolecular design.

Lossy Mode Resonance Optical Fiber Enhanced by Electrochemical-Molecularly Imprinted Polymers for Glucose Detection.

Noninvasive glucose sensors are emergent intelligent sensors for analyzing glucose concentration in body fluids within invasion-free conditions. Conventional glucose sensors are often limited by a number of issues such as invasive and real-time detection, creating challenges in continuously characterizing biomarkers or subtle binding dynamics. In this study, we introduce an efficient lossy mode resonance (LMR) optical fiber sensor incorporating the molecularly imprinted polymers (MIPs) to amplify glucose molecules. A molecularly imprinted recognition platform is created on an LMR sensor surface through a convenient one-step electrochemical (EC) polymerization method, in which 3-Aminophenylboric acid and glucose serve as the functional monomer and template molecule, respectively. LMR resonance wavelength shift induced by the coupling of the optical lossy mode and the fiber core mode is employed as the parameter to characterize biomolecules. Due to its high sensitivity to surrounding environment changes, a limit of detection (LOD) of 4.62 × 10-2 μmol/L for glucose can be achieved by this optical fiber sensor. Additionally, the prepared EC-MIPs LMR sensor is capable of detecting glucose molecules in human saliva samples with high accuracy, endowing its potential for practical applications.

Molecularly Imprinted Electrochemical Sensor Constructed by Ferrocene‐Functionalized Carbon Nanotubes for Rapid Recognition and Determination of Tryptophan

AbstractMolecular imprinting is an advanced technology in the fabrication of novel chemical sensors recently applied, enabling rapid responses and highly selective binding to specific molecules, thereby enabling efficient detection of material constituents. In this study, a new molecularly imprinted electrochemical sensor (MIES) utilizing ferrocene‐functionalized carbon‐nanotubes (Fc‐CNTs) was developed for the determination of tryptophan (Trp). The formation of molecularly imprinted polymer (MIP) involves polymerization in dimethyl sulfoxide (DMSO) using Trp, methacrylic acid (MAA) and ethylene glycol dimethacrylate (EGDMA) as the template molecules, functional monomers, and cross‐linking agents, respectively. Due to the modification of MIPs, the sensor achieves high performance. The sensor demonstrates a linear range from 1 to 45 μM and from 45 to 330 μM, with the limit of detection of 0.44 μM, exceeding that of the majority of sensors reported in the literature. Furthermore, the sensor can effectively detect Trp in real samples, including human serum and amino acid oral liquid. The recovery rate of Trp in human serum samples is 94.2 % to 105.30 %, and in amino acid oral liquid is 94.3 % to 101.68 %. This study provides a promising approach for the effective detection and analysis of tryptophan constituents.

3D Fluorescence Spectroscopy Combined With Chemometrics as a Tool for Control of Imprinted Protein Purification From Template Molecules

ABSTRACTImprinted proteins (IPs) are promising alternatives to natural recognition systems, such as biological receptors or antibodies. One of the crucial stages during development of IPs is removal of the template molecules from its complex with the protein. In this study, bovine serum albumin was imprinted in the presence of 4‐hydroxycoumarin (4‐HC); purification of IPs were carried out by dialysis, and fluorescence 3D spectroscopy was used to monitor the IP purification process. Excitation–emission matrix (EEM) was further investigated via several chemometric algorithms (principal component analysis [PCA], parallel factor analysis [PARAFAC], and independent components analysis [ICA]). We found that the models using PARAFAC and ICA worked better than those of PCA. It was shown that PARAFAC and ICA analyses allow not only to recognize IP sample with signal close to nonimprinted protein, but also to provide recommendations on the optimal dialysis time.

Molecularly imprinted composite membranes with the dual imprinted network for highly selective separation of acteoside

Acteoside (ACT) is the main active ingredient in phenylethanoid glycosides (PhGs) and it has anti-inflammatory, liver-protecting, and memory-enhancing functions. It remained a challenge to develop an imprinted membrane with high permselectivity for separation of ACT from PhGs. In this paper, ACT was used as a template molecule to design dual imprinted molecularly imprinted composite membranes (DIMICMs). The dual imprinted network structure was constructed and played a vital role in DIMICMs. On one hand, ACT imprinted network was formed on the surface of ACT-KH570/PDA/CMK-3@PVDF, and it can recognize and adsorb ACT. On the other hand, the imprinted filler ACT-KH570/PDA/CMK-3 was mixed with PVDF powder to construct the ACT imprinted network in the membrane, and the imprinted network can further recognize and accommodate the ACT. The dual imprinted network acted synergistically for dual recognition of ACT. The result showed that the DIMICMs had the high permselectivity (β = 14.61), selectivity (α = 4.64) and rebinding capacity (105.58 mg/g). The designed approach of DIMICMs with a dual imprintednetwork provided a strategy for the separation of natural products.

Analysis of Trace Enrofloxacin in Environmental Waters by a Surface Molecular Imprinting Technique.

Surface-imprinted polymers (ZIF-67@MIPs) supported by ZIF-67 were prepared by precipitation polymerization using enrofloxacin (ENR) as the template molecule, methacrylic acid as the functional monomer, and ethylene glycol dimethacrylate as the cross-linker. ZIF-67@MIPs were characterized by Fourier transform infrared spectrometry, X-ray diffraction, scanning electron microscopy, and particle size distribution. The adsorption performance of the polymer was studied. The adsorption equilibrium was reached within 30 min. The maximum adsorption was 9.02 μg·mg-1. The imprinting factor was 2.58. The polymer was then used as a sorbent of a solid-phase extraction column for the separation and purification of ENR in real water samples. The extraction conditions were optimized. The method was established by high-performance liquid chromatography, and the linearity was verified by UPLC-MSMS. The correlation coefficient and limits of detection and quantification were 0.9999, 0.23 ng·mL-1, and 0.76 ng·mL-1, respectively. The recoveries were in the range of 83.79-100.68%; the relative standard deviation was 4.46-7.35%. The above data indicated that the method could be used for the separation and enrichment of ENR in real samples.

A magnetic SERS-imprinted sensor for the determination of cardiac troponin I based on proteolytic peptide technology

Acute myocardial infarction is a sudden and high-mortality disease that can be accurately diagnosed by measuring the level of cardiac troponin I in the blood. Currently, cTnI commonly used clinical detection methods usually have excellent sensitivity and are suitable for large-scale sample detection analysis. However, most of these methods are operated through multiple steps of fixation, incubation, reaction and separation, and most of them require professionals to operate complex instruments, which greatly limits their applicability in real-time rapid detection. Therefore, a method that requires low professional skills and can perform rapid detection is necessary. We presents an alternative strategy to quantify cTnI in clinical serum samples using a combination of SERS and magnetic molecularly imprinted polymers (MMIP). MMIPs was synthesized under Polyvinyl Pyrrolidone (PVP) conditions without vinyl modification using characteristic peptide as template, MAA and DMAm as functional monomers. The internal Raman probe 4-MBA was connected through Ag-SH bonds in MMIPs to solve the problem that the target object had no Raman characteristic peak. MMIPs with high magnetic and adsorptive properties showed characteristic absorption peaks at the Raman shift of 1582 cm−1 after specific capture of the target templates. The Raman signals of the 4-MBA were reduced due to shielding effects and the detection range of this method was 0.001–100 ng mL−1. The recoveries and relative standard deviations (RSDs) of the spiked experiments were 103.1%–106.3 % and 3.54 %–7.38 %, respectively. In summary, this work had appropriate sensitivity and specificity, and there was no significant difference in detection results after ELISA verification. It provided a flexible and practical analysis method for detecting cTnI based on SERS technology. In addition, the imprinting materials of other disease markers can be prepared by changing the template molecules, which provides a new idea for the detection of other biomarkers.

A novel molecularly imprinted electrochemical sensor based on MnO-Fe3O4@C was designed with DFT theoretical study for the detection of thiamphenicol in food

In this study, a new molecularly imprinted electrochemical sensor is presented for thiamphenicol (TAP) based on MnO-Fe3O4@C and a molecularly imprinted polymer (MIP). In the synthesis process of MIP, the density functional theory (DFT) was applied to simulated the interaction between different functional monomers and template molecules, and screen the optimal functional monomers and the ratio of optimal template molecules to functional monomers, which guided the electrochemical in-situ polymerization of MIP. The composite materials were evaluated by X-ray photoelectron spectroscopy (XPS), X-ray diffraction (XRD), energy dispersive spectroscopy (EDS), transmission electron microscopy (TEM) and scanning electron microscopy (SEM), and the electrochemical performance of molecular imprinted electrode was evaluated by cyclic voltammetry (CV), differential pulse voltammetry (DPV) and electrochemical impedance spectroscopy (EIS). Under the optimal conditions, there is a strong linear correlation between the current response and TAP concentration in the 0.01–1 μM (R2=0.9988) and 1–40 μM (R2=0.9954) range. The lowest detection limit (S/N = 3) was 0.007 μM. Besides, the sensor has good reproducibility, stability and anti-interference ability, and has successfully detected analytes in milk and egg samples, which provides application prospects for constructing selective detection of TAP in food samples.

Detection of piperine content in black pepper using a molecular imprinted poly(N,N-dimethylacrylamide) embedded graphite electrode: A machine learning based prediction approach

The paper presents a molecular imprinted graphite electrode for selective and sensitive detection of piperine (1-Propylpiperidine) in Piper nigrum (black pepper). Poly(N,N-dimethylacrylamide) (PDMAM) was utilized as a functional monomer directing polymerization of uniform molecularly imprinted polymer (MIP) layers on the surface of the graphite layer using ethylene glycol dimethacrylate (EGDMA) as cross-linker with piperine (PIP) as template molecules. The formation of imprinting, non-imprinting, and elution of analytes within the polymer matrix were studied by field emission scanning electron microscope (FESEM), Fourier transform infrared (FTIR), UV–visible (UV–Vis) and X-ray photoelectron spectroscopy (XPS). The electrochemical response of piperine was evaluated through differential pulse voltammetry (DPV) using a PDMAM-MIP@G electrode that showed an oxidation peak at 1.25 ± 0.15 V. Under optimized experimental conditions, DPV peak currents were linear over two concentration ranges (0.001–1 µM and 1–200 µM). A limit of detection (LOD) was found to be 0.0006 µM. Developed electrode yielded high selectivity, sensitivity (12.92 µA/µM (lower linear range) and 0.33 µA/µM (upper linear range)), promising reproducibility, long-term stability (3.85 % decrease in response over 28 days), and interference immunity. The developed PDMAM-MIP@G electrode was applied to real samples using four branded pepper powder procured from local market and the sensor data was recorded. A convolutional neural network (CNN) driven prediction model has been proposed to predict the piperine concentration. Among the four CNN models tested, the best model, averaged over 50 runs, achieved a mean absolute error (MAE) of 0.268, a mean prediction error of 2.35 %, and a R-squared value of 0.93 on the testing set when compared with reference values obtained from reverse-phase high-performance liquid chromatography (RP-HPLC).

Flavonoids as potential SARS-CoV-2 main protease inhibitors: In vitro activity evaluation, molecular docking, 3D-QSAR investigation and synthesis

The damage to public health posed by the COVID-19 epidemic remains non-negligible, and research into highly effective antiviral drugs is key to addressing the epidemic. The main protease (Mpro) is critical for SARS-CoV-2 replication and acts as an effective target for drug development. To date, many flavonoid compounds have been reported to exhibit inhibition of Mpro, and flavonoid structures are informative for the development of new inhibitors. In the present study, we first evaluated the ability of 35 flavonoid compounds to bind Mpro and found that the hydrophobic interaction generated between the benzene ring and the residues may be the main source of binding force. The in vitro inhibitory activity of these compounds was tested by the FRET method, and most of them showed significant inhibition of Mpro. Preliminary analysis revealed that the presence of the glycosidic group was detrimental to the activity of the compounds, in addition the position of the hydroxyl substituent had an effect on the activity of the compounds. Reliable and predictive CoMFA (q2 = 0.541, r2 = 0.998, SEE = 0.039) and CoMISA (q2 = 0.554, r2 = 0.999, SEE = 0.034) models were developed, and the compounds were analyzed by 3D-QSAR with modeled steric, electrostatic, hydrogen bond donor, and hydrophobic fields. A series of compounds were synthesized and characterized, which showed similar experimental and predicted activities, with the activity of 15d (IC50 = 0.74 ± 0.04 uM) exceeding that of the template molecule 15 (0.98 ± 0.13 uM). Subsequently, molecular docking revealed the binding mode of 15d to Mpro and verified the predictions of steric, hydrogen bond donor, and hydrophobic field. In conclusion, these findings provide ideas for subsequent structural studies of flavonoids that could be used in the development of flavonoid-type SARS-CoV-2 Mpro inhibitors.