Mechanism of the antimicrobial activity induced by phosphatase inhibitor sodium ortho-vanadate.

The present study describes a novel antimicrobial mechanism based on Sodium Orthovanadate (SOV), an alkaline phosphatase inhibitor. Scanning electron microscopy (SEM), transmission electron microscopy (TEM) and atomic force microscopy (AFM) were employed to examine the surface morphologies of the test organism, Escherichia coli (E. coli), during various antibacterial phases. Our results indicated that SOV kills bacteria by attacking cell wall growth and development, leaving E. coli's outer membrane intact. Our antimicrobial test indicated that the MIC of SOV for both E. coli and Lactococcus lactis (L. lactis) is 40 µM. A combination of quantum mechanical calculations and vibrational spectroscopy revealed that divanadate from SOV strongly coordinates with Ca2+ and Mg2+, which are the activity centers for the phosphatase that regulates bacterial cell wall synthesis. The current study is the first to propose the antibacterial mechanism caused by SOV attacking cell wall.

Novel carbon nanozymes with enhanced phosphatase-like catalytic activity for antimicrobial applications.

In this work, Sulfur and Nitrogen co-doped carbon nanoparticles (SN-CNPs) were synthesized by hydrothermal method using dried beet powder as the carbon source. TEM and AFM images indicated that these SN-CNPs form a round-shape ball with an approximate diameter of 50 nm. The presence of Sulfur and Nitrogen in these carbon-based nanoparticles was confirmed by FTIR and XPS analyses. These SN-CNPs were found to have strong phosphatase-like enzymatic activity. The enzymatic behavior of SN-CNPs follows the Michaelis-Menten mechanism with greater vmax and much lower Km values compared to alkaline phosphatase. Their antimicrobial properties were tested on E. coli and L. lactis, with MIC values of 63 µg mL-1 and 250 µg mL-1, respectively. SEM and AFM images of fixed and live E. coli cells revealed that SN-CNPs strongly interacted with the outer membranes of bacterial cells, significantly increasing the cell surface roughness. The chemical interaction between SN-CNPs and phospholipid modeled using quantum mechanical calculations further support our hypothesis that the phosphatase and antimicrobial properties of SN-CNPs are due to the thiol group on the SN-CNPs, which is a mimic of the cysteine-based protein phosphatase. The present work is the first to report carbon-based nanoparticles with strong phosphatase activity and propose a phosphatase natured antimicrobial mechanism. This novel class of carbon nanozymes has the potential to be used for effective catalytic and antibacterial applications.

Fluorescent nano-sized aggregates of halogen bonded complexes formed using perfluoropropyl iodides: a systematic comparison between two isomeric halogen bond acceptors, aniline and 4-methyl pyridine.

The halogen bonds (XB) formed by the two isomers 4-methyl pyridine (MePy) and aniline (ANL) with heptafluoro-1-propyl iodide (n-C3F7I) and heptafluoro-2-propyl iodide (iso-C3F7I) were investigated using vibrational (FT-IR and Raman) spectroscopy and quantum mechanical calculations. While these two isomers indicated a distinctive impact on the ring related vibrations, molecular electrostatic potential, frontier molecular orbitals, intermolecular electron density delocalisation and consequential charge transfer upon halogen bonding with n-C3F7I and iso-C3F7I, the dramatic intermolecular charge transfer (CT) occurring on the MePy involved XB systems demonstrated an ion-pair like aggregation. Such aggregation, after 72 h and longer after mixing, leads to an emission of fluorescence for both [MePy·C3F7I] systems. The resulting nano-sized aggregates were characterised using UV-Vis absorption and fluorescence spectroscopy along with scanning and transmittance electron microscopy (SEM and TEM), wherein, the XB complex with iso-C3F7I showed a faster and more severe aggregation due to a stronger CT than that with n-C3F7I. The present work is the first case of aggregation induced emission (AIE) due to aggregation of XB complexes formed by small neutral molecules.

Intermolecular interactions in the crystalline structure of some polyhalogenated Di- And triamino Pyridines: Spectroscopical perspectives.

Supramolecular synthon is identified as a unit and provides important structural and energetic information in the study of organic crystals. However, the direct estimation of the supramolecular interaction remains challenging. In the present work six polyhalogenated di- or triamino pyridines were synthesised, their crystalline structure was characterised, and corresponding supramolecular synthons were studied using a combination of quantum mechanical calculations and FT-IR and Raman spectroscopy. Some distinctive features were identified especially for three vibrational normal modes (RNMs) related to the pyridine ring (viz. RNM1, RNM3 and RNM7) in the vibrational spectra (FT-IR and Raman) of the solid samples, which are due to the supramolecular interactions, hydrogen bond (hb) in particular, according to the quantum mechanical calculations. The comparison between the IR and Raman spectra of experimental and simulated results indicates that the adjacent intermolecular hydrogen bonds between two same molecules extensively exist in the solid samples. Moreover, some quantitative correlation was established among the dimerisation energies for hb dimers (hb1 dimers for compounds 1 and 2), the ring structure defined by the distribution of the substituents and quantitative characteristics of the vibrational spectra, for instance, the splitting magnitudes for RNM3(2) in IR spectra and the peak gap between RNM1 and RNM2 in Raman spectra.

Network pharmacology and experimental investigation of Rhizoma polygonati extract targeted kinase with herbzyme activity for potent drug delivery.

Rhizoma polygonati (Huangjing, RP) has been used for a long history with many chemical components in inducing anti-cancer, anti-aging, anti-diabetes, anti-fatigue, and more prevention of diseases or acts as nutrition sources in food. Here we investigated RP extract combination with kinase inhibitors in anti-cell growth and blockade in pathways targeting kinases. Experimental investigation and network pharmacology analysis were applied to test the potent kinase-mediated signaling. Herbzyme activity was determined by substrate with optical density measurement. Extract of processed RP inhibits cell growth in a much greater manner than alone when applied in combination with inhibitors of mTOR or EGFR. Moreover, processing methods of RP from Mount Tai (RP-Mount Tai) play essential roles in herbzyme activity of phosphatase suggesting the interface is also essential, in addition to the chemical component. The network pharmacology analysis showed the chemical component and target networks involving AKT and mTOR, which is consistent with experimental validation. Finally, EGFR inhibitor could be associated with nano-extract of RP-Mount Tai but not significantly affects the phosphatase herbzyme activity in vitro. Thus the processed extract of RP-Mount Tai may play a dual role in the inhibition of cell proliferation signaling by both chemical component and nanoscale herbzyme of phosphatase activity to inhibit kinases including mTOR/AKT in potent drug delivery of kinase inhibitors.

Nano-evolution and protein-based enzymatic evolution predicts novel types of natural product nanozymes of traditional Chinese medicine: cases of herbzymes of Taishan-Huangjing (Rhizoma polygonati) and Goji (Lycium chinense).

Nanozymes and natural product-derived herbzymes have been identified in different types of enzymes simulating the natural protein-based enzyme function. How to explore and predict enzyme types of novel nanozymes when synthesized remains elusive. An informed analysis might be useful for the prediction. Here, we applied a protein-evolution analysis method to predict novel types of enzymes with experimental validation. First, reported nanozymes were analyzed by chemical classification and nano-evolution. We found that nanozymes are predominantly classified as protein-based EC1 oxidoreductase. In comparison, we analyzed the evolution of protein-based natural enzymes by a phylogenetic tree and the most conserved enzymes were found to be peroxidase and lyase. Therefore, the natural products of Rhizoma polygonati and Goji herbs were analyzed to explore and test the potent new types of natural nanozymes/herbzymes using the simplicity simulation of natural protein enzyme evolution as they contain these conserved enzyme types. The experimental validation showed that the natural products from the total extract of nanoscale traditional Chinese medicine Huangjing (RP, Rhizoma polygonati) from Mount-Tai (Taishan) exhibit fructose-bisphosphate aldolase of lyase while nanoscale Goji (Lycium chinense) extract exhibits peroxidase activities. Thus, the bioinformatics analysis would provide an additional tool for the virtual discovery of natural product nanozymes.

Generation of particle assemblies mimicking enzymatic activity by processing of herbal food: the case of rhizoma polygonati and other natural ingredients in traditional Chinese medicine.

Processed herbs have been widely used in eastern and western medicine; however, the mechanism of their medicinal effects has not yet been revealed. It is commonly believed that a central role is played by chemically active molecules produced by the herbs' metabolism. In this work, processed rhizoma polygonati (RP) and other herbal foods are shown to exhibit intrinsic phosphatase-like (PL) activity bounded with the formation of nano-size flower-shaped assembly. Via quantum mechanical calculations, an enzymatic mechanism is proposed. The enzymatic activity may be induced by the interaction between the sugar molecules distributed on the surface of the nanoassemblies and the phosphatase substrate via either a hydroxyl group or the deprotonated hydroxyl group. Meanwhile, the investigation was further extended by processing some fresh herbs and herbal food through a similar protocol, wherein other enzymatic activities (such as protease, and amylase) were observed. The PL activity exhibited by the processed natural herbs was found to be able to effectively inhibit cancer cell growth via phosphatase signaling, possibly by crosstalk with kinase signaling or DNA damage by either directly binding or unwinding of DNA, as evidenced by high-resolution atomic-force microscopy (HR-AFM). In this work, the neologism herbzyme (herb + enzyme) is proposed. This study represents the first case of scientific literature introducing this new term. Besides the well-known pharmacological properties of the natural molecules contained in herbs and herbal food, there exists an enzymatic/co-enzymatic activity attributed to the nanosized assemblies.

Rhizoma polygonati from Mount Tai: nutritional value and usefulness as a traditional Chinese medicine, source of herbzyme, and potential remediating agent for COVID-19 and chronic and hidden hunger.

Recently, traditional Chinese medicine-based treatment has succeeded in fighting coronavirus disease 2019 (COVID-19), and Rhizoma polygonati (Huangjing) has been one of the recommended components. Its processed products play antidiabetic, antiviral, antitumor, antioxidation, antifatigue, antiaging, and immune enhancement roles. The climate in Mount Tai is mild, and the dense forest is suitable for the growth of Rhizome polygonati, which has gradually evolved into a unique specie. Considering the important medicinal value and pleasant taste of Mount Tai-Rhizoma polygonati, various healthy and functional food products, controlled by quality markers with anti-COVID-19 potential, as well as emergency foods can be developed. The study aimed to review current evidence on the nutritional value of Rhizoma polygonati from Mount Tai and its usefulness as a traditional Chinese medicine, source of herbzyme, and potential remediating agent for COVID-19 and food shortage. Most recent findings regarding herbal nanomedicine have revealed that nanoscale chemical compounds are potentially efficient in drug delivery or nanozyme catalysis upon bioprocessing. Nanoflower structure is found in processed Rhizoma polygonati by self-assembly and has wide application in enzymatic events, particularly nanoscale herbzyme. The novel findings regarding Mount Tai-Rhizoma polygonati could enhance its novel applications in chronic and hidden hunger, clinical nanomedicine, and as an anti-COVID-19 agent.