Natural Organic Molecules Research Articles

Self-assembly variation of glycyrrhetinic acid epimers: Assembly mechanism and antibacterial efficacy between 18 α-GA and 18 β-GA

Studies have confirmed that the spatial arrangement of chiral molecules has a decisive influence on supramolecular assembly. However, the effect of epimerization caused by the change of a single chiral center on the self-assembly of chiral molecules has not been reported. Herein, we explored a pair of epimers 18 α-glycyrrhetinic acid and 18 β-glycyrrhetinic acid from Glycyrrhiza uralensis Fisch, which had completely different medicinal activities. In this study, we found that these epimers of glycyrrhetinic acid showed distinct self-assembly properties under the condition of the deionized water and a small amount of DMSO solution. Interestingly, the cis-configured 18 β-GA could form a 'head-to-tail' interlaced structure and further self-assembled to form nanoparticles, while trans-configured 18 α-GA was connected in a “head-to-head” manner, and due to the excessive steric hindrance that made it difficult to assemble. This work not only clearly demonstrates the impact of epimerization due to changes in a single chiral center on the self-assembly of chiral molecules as well as biological activity, but also provides new insights into the self-assembly of natural organic molecules in the development of nanomedicines and biofunctional materials.

Changing Cinnamaldehyde Skeleton Achieves Antibacterial Nanoswitch.

Changeable substituent groups of organic molecules can provide an opportunity to clarify the antibacterial mechanism of organic molecules by tuning the electron cloud density of their skeleton. However, understanding the antibacterial mechanism of organic molecules is challenging. Herein, we reported a molecular view strategy for clarifying the antibacterial switch mechanism by tuning electron cloud density of cinnamaldehyde molecule skeleton. The cinnamaldehyde and its derivatives were self-assembled into nanosheets with excellent water solubility, respectively. The experimental results show that α-bromocinnamaldehyde (BCA) nanosheets exhibits unprecedented antibacterial activity, but there is no antibacterial activity for α-methylcinnamaldehyde nanosheets. Therefore, the BCA nanosheets and α-methylcinnamaldehyde nanosheets achieve an antibacterial switch. Theoretical calculations further confirmed that the electron-withdrawing substituent of the bromine atom leads to a lower electron cloud density of the aldehyde group than that of the electron-donor substituent of the methyl group at the α-position of the cinnamaldehyde skeleton, which is a key point in elucidating the antimicrobial switch mechanism. The excellent biocompatibility of BCA nanosheets was confirmed by CCK-8. The mouse wound infection model, H&E staining, and the crawling ability of drosophila larvae show that as-prepared BCA nanosheets are safe and promising for wound healing. This study provides a new strategy for the synthesis of low-cost organic nanomaterials with good biocompatibility. It is expected to expand the application of natural organic small molecule materials in antimicrobial agents.

Bacterial Hydrazine Biosynthetic Pathways Featuring Cupin/Methionyl tRNA Synthetase-like Enzymes.

Nitrogen-Nitrogen (N-N) bond-containing functional groups in natural products and synthetic drugs play significant roles in exerting biological activities. The mechanisms of N-N bond formation in natural organic molecules have garnered increasing attention over the decades. Recent advances have illuminated various enzymatic and nonenzymatic strategies, and our understanding of natural N-N bond construction is rapidly expanding. A group of didomain proteins with zinc-binding cupin/methionyl-tRNA synthetase (MetRS)-like domains, also known as hydrazine synthetases, generates amino acid-based hydrazines, which serve as key biosynthetic precursors of diverse N-N bond-containing functionalities such as hydrazone, diazo, triazene, pyrazole, and pyridazinone groups. In this review, we summarize the current knowledge on hydrazine synthetase mechanisms and the various pathways employing this unique bond-forming machinery.

Natural organic small molecules promote the aging of plastic wastes and refractory carbon decomposition in water

Microplastics and nanoplastics are ubiquitous in rivers and undergo environmental aging. However, the molecular mechanisms of plastic aging and the in-depth effects of aging on ecological functions remain unclear in waters. The synergies of microplastics and nanoplastics (polystyrene as an example) with natural organic small molecules (e.g., natural hyaluronic acid and vitamin C related to biological tissue decomposition) are the key to producing radicals (•OH and •C). The radicals promote the formation of bubbles on plastic surfaces and generate derivatives of plastics such as monomer and dimer styrene. Nanoplastics are easier to age than microplastics. Pristine plastics inhibit the microbial Shannon diversity index and evenness, but the opposite results are observed for aging plastics. Pristine plastics curb pectin decomposition (an indicator of plant-originated refractory carbon), but aging plastics promote pectin decomposition. Microplastics and nanoplastics undergoing aging processes enhance the carbon biogeochemical cycle. For example, the increased carbohydrate active enzyme diversity, especially the related glycoside hydrolase and functional species Pseudomonas and Clostridium, contributes to refractory carbon decomposition. Different from the well-studied toxicity and aging of plastic pollutants, this study connects plastic pollutants with biological tissue decomposition, biodiversity and climate change together in rivers.

Magnetic nanoparticle loading and application of weak magnetic field to reconstruct the cake layer of coagulation-ultrafiltration process to achieve efficient antifouling: Performance and mechanism analysis

Abandoning the costly development of new membrane materials and instead directly remodeling the naturally occurring cake layer constitutes a dynamic, low-cost, long-lasting, and proactive strategy to "fight fouling with fouling". Several optimization strategies, including coagulation/modified magnetic seed loading and applying a weak magnetic force (0.01T) at the ultrafiltration end, improved the anti-fouling, retention, and sieving performances of conventional ultrafiltration process during the treatment of source water having complex natural organic matter (NOMs) and small molecule micropollutants. Two modified magnetic seeds we prepared were composite nano-seed particles (Fe3O4@SiO2-NH2 (FS) and Fe3O4@SiO2@PAMAM-NH2 (FSP)). Aim of the study was to regulate the formation of cake layer via comprehensive testing of the antifouling properties of optimized processes and related mechanistic studies. It was found to be essential to enhance the interception of xanthate and tryptophan proteins in the cake layer for improving the anti-fouling performance based on the correlation and redundancy analyses, while the use of modified magnetic seeds and magnetic field showed a significant positive impact on water production. Blockage modeling demonstrated the ability to form a mature cake layer during the initial filtration stage swiftly. This mitigated the risk of irreversible fouling caused by pore blockage during the early stage of coagulation-ultrafiltration. Morphologically, the reconstructed cake layer exhibited elevated surface porosity, an internal cavity channel structure, and enhanced roughness that can promote increased water flux and retention of water impurities. These optimized the maturity of the cake layer in both time and space. Density Functional Theory (DFT), Extended Derjaguin-Landau-Verwey-Overbeek (XDLVO) theory, and Modified Extended Derjaguin-Landau-Verwey-Overbeek (MDLVO) calculations indicated aggregation behavior of matter on the cake layer to be enhanced effectively due to magnetic seed loading. This is mainly due to the strengthening of polar interactions, including hydrogen bonding, π-π* conjugation, etc., which can happen between the cake layer loaded with FSP and the organic matter. Under the influence of a magnetic field, magnetic force energy (VMF) significantly impacts the system by eliminating energy barriers. This research will provide innovative strategies for effectively purifying intricate source water through ultrafiltration while controlling membrane fouling.

Detecting Structural Environments of Carboxyl Groups in Dissolved Natural Organic Molecules

Detecting Structural Environments of Carboxyl Groups in Dissolved Natural Organic Molecules

Inorganic Nanoparticles–Driven Self–Assembly of natural small molecules in water for constructing multifunctional nanocapsules against plant diseases

Directly constructing nanoparticles through the self–assembly of natural small molecules in aqueous media presents many opportunities for crop protection; however, this special strategy is hindered by the lack of simple and cost–effective preparation methods to date. Herein, we report a facile strategy for constructing multifunctional natural nanocapsules for treating plant diseases based on the special coassembly of natural small organic molecules and inorganic nanoparticles. In aqueous conditions, uniform curcumin nanocapsules (ZnO@Cur) are assembled through electrostatic interactions, coordination effects and hydration effects as mediated by trace of nanoscale zinc oxide. The nanocapsules obtained can be further modified to enhance stability by introducing a polydopamine coating (ZnO@Cur@PDA). The antibacterial activity of ZnO@Cur@PDA against plant-pathogenic bacteria was better than that of curcumin, ZnO NPs, ZnO@Cur and zinc thiazole in vitro. The nanocapsules effectively kill plant–pathogenic bacteria via tight binding to the bacterial surface, inducing reactive oxygen species accumulation and disrupting bacterial cell walls. ZnO@Cur@PDA display strong activities against rice bacterial blight with protective activity of 64.0 % and curative activity of 62.2%, which is much better than commercial drugs bismerthiazol (protective activity of 33.0 % and curative activity of 38.4%) and zinc thiazole(protective activity of 38.6 % and curative activity of 31.8%). ZnO@Cur@PDA display adequate washing resistance, and low rice plant toxicity; furthermore, they are degradable. Additionally, both the inner cavities and outer surfaces of nanocapsules bear abundant sites and spaces that can be further tuned for loading other pesticide molecules or flexible construct complex multifunctional nanoparticles. Our study should encourage further development in the coassembly of organic and inorganic materials via green processes for effective and tunable nanopesticides.

Molecular docking in organic, inorganic, and hybrid systems: a tutorial review.

Molecular docking simulation is a very popular and well-established computational approach and has been extensively used to understand molecular interactions between a natural organic molecule (ideally taken as a receptor) such as an enzyme, protein, DNA, RNA and a natural or synthetic organic/inorganic molecule (considered as a ligand). But the implementation of docking ideas to synthetic organic, inorganic, or hybrid systems is very limited with respect to their use as a receptor despite their huge popularity in different experimental systems. In this context, molecular docking can be an efficient computational tool for understanding the role of intermolecular interactions in hybrid systems that can help in designing materials on mesoscale for different applications. The current review focuses on the implementation of the docking method in organic, inorganic, and hybrid systems along with examples from different case studies. We describe different resources, including databases and tools required in the docking study and applications. The concept of docking techniques, types of docking models, and the role of different intermolecular interactions involved in the docking process to understand the binding mechanisms are explained. Finally, the challenges and limitations of dockings are also discussed in this review.

On binding mechanism exploration of organic amphoteric dye Rhodamine B with natural polymeric DNA

Nucleic acids, like DNA and RNA, are molecules that are present in any life form. Their most notable function is to encode biological information. DNA also has unique material properties, which attract material scientists, nanotechnologists, and engineers. The study and investigation of the structural and dynamical properties of complex biological systems have attracted considerable interest among scientists in general and physicists and biologists in particular.The alteration in DNA due to the introduction of any small molecule changes the overall function and stability of DNA. So quantitative information about the effects of such ligand binding on the structure and function of DNAs, are very much required. In this study, the interaction between natural polymeric DNA (deoxyribonucleic acid sodium salt from herring testes; derived from the sperm of herring fish) and organic amphoteric dye molecule (fluorescent, biomarker), Rhodamine B, has been studied quantitatively. An overview of the overall changes occurring in the macromolecule was estimated using multi-spectroscopic methods and complemented with computational analyses. The results obtained provide an understanding of the binding affinity, stoichiometry, and structural details of the ligand-DNA complex, followed by an estimation of associated binding thermodynamics. Finally, structure–function relationships and molecular aspects of ligand binding to DNA have been established in the current piece of research work, which can have multifaceted applications in drug development and pharmacology.

Diverse Alkyl-Silyl Cross-Coupling via Homolysis of Unactivated C(sp3)-O Bonds with the Cooperation of Gold Nanoparticles and Amphoteric Zirconium Oxides.

Since C(sp3)-O bonds are a ubiquitous chemical motif in both natural and artificial organic molecules, the universal transformation of C(sp3)-O bonds will be a key technology for achieving carbon neutrality. We report herein that gold nanoparticles supported on amphoteric metal oxides, namely, ZrO2, efficiently generated alkyl radicals via homolysis of unactivated C(sp3)-O bonds, which consequently promoted C(sp3)-Si bond formation to give diverse organosilicon compounds. A wide array of esters and ethers, which are either commercially available or easily synthesized from alcohols participated in the heterogeneous gold-catalyzed silylation by disilanes to give diverse alkyl-, allyl-, benzyl-, and allenyl silanes in high yields. In addition, this novel reaction technology for C(sp3)-O bond transformation could be applied to the upcycling of polyesters, i.e., the degradation of polyesters and the synthesis of organosilanes were realized concurrently by the unique catalysis of supported gold nanoparticles. Mechanistic studies corroborated the notion that the generation of alkyl radicals is involved in C(sp3)-Si coupling and the cooperation of gold and an acid-base pair on ZrO2 is responsible for the homolysis of stable C(sp3)-O bonds. The high reusability and air tolerance of the heterogeneous gold catalysts as well as a simple, scalable, and green reaction system enabled the practical synthesis of diverse organosilicon compounds.

Substituted Isocoumarins: An Assemble of Synthetic Strategies Towards 3-Substituted and 3,4-Disubstituted Isocoumarins.

The versatility of isocoumarin frameworks offers the privilege to access many pharmacological targets. This unique heterocycle core present in many natural products and complex organic molecules contribute to medicinal chemistry as anti-cancer, anti-inflammatory and immunomodulatory agents. The attractive properties exhibited by its analogues urged the scientists to explore their synthetic analogues. In regard to the myriads of synthetic methodologies, we have compiled a review update covering all the articles that have been published towards the synthesis of 3-substituted and 3,4-disubstituted isocoumarins. Additionally, we have also highlighted a systematic survey of catalytic methods for their synthesis along with their scope towards diverse functionalizations and plausible mechanistic aspects.

Albumin-based nanosystem for dual-modality imaging-guided chem-phototherapy against immune-cold triple-negative breast cancer.

Triple-negative breast cancer is a highly aggressive and metastatic tumor; diagnosing it in the early stages is still difficult, and the prognosis for conventional radio-chemotherapy and immunotreatment is not promising due to cancer's immunosuppressive microenvironment. The utilization of protein-based nanosystem has proven to be effective in delivering agents with limited adverse effects, yet the combination of diagnosis and treatment remains a difficult challenge. This research took advantage of natural albumin and organic molecules to construct a self-assemble core-shell nanostructure combining with superparamagnetic iron oxide nanocrystals and heptamethine cyanine dye IR780 through non-covalent interactions. This nanocomposite successfully decreased the transverse relaxation time of the magnetic resonance hydrogen nucleus, resulting in outstanding T2 imaging, as well as emitting near-infrared II fluorescence, thereby the resulting dual-modality imaging tool was applied to improve diagnostic competency. It is noteworthy that the nanocomposites exhibited impressive enzyme-like catalytic and photothermal capabilities, resulting in a successful activation of the immune system to efficiently suppress distant metastatic lesions in vivo. Consequently, this nano-drug-based therapy could be an advantageous asset in reinforcing the immune system and hindering the growth and reappearance of the immune-cold breast cancer.

Mechanochemical Defluorinative Arylation of Trifluoroacetamides: An Entry to Aromatic Amides

The amide bond is prominent in natural and synthetic organic molecules endowed with activity in various fields. Among a wide array of amide synthetic methods, substitution on a pre-existing (O)C-N moiety is an underexplored strategy for the synthesis of amides. In this work, we disclose a new protocol for the defluorinative arylation of aliphatic and aromatic trifluoroacetamides yielding aromatic amides. The mechanochemically induced reaction of either arylboronic acids, trimethoxyphenylsilanes, diaryliodonium salts, or dimethyl(phenyl)sulfonium salts with trifluoroacetamides affords substituted aromatic amides in good to excellent yields. These nickel-catalyzed reactions are enabled by C-CF3 bond activation using Dy2O3 as an additive. The current protocol provides versatile and scalable routes for accessing a wide variety of substituted aromatic amides. Moreover, the protocol described in this work overcomes the drawbacks and limitations in the previously reported methods.

Recovery of Lac Resin from the Aqueous Effluent of Shellac Industry

Shellac and aleuritic acid manufacturing industries generate a lot of alkaline aqueous effluent during the process of manufacture of shellac and aleuritic acid from the seedlac/sticklac. The generated effluent contains lac resin, lac wax, lac dye and other water-soluble organic acids. Shellac industries in India face problems with the disposal of aqueous effluent due to the presence of considerable amounts of natural organic molecules and the dark colour solution. To address these problems, we have developed a novel method for the selective recovery of the lac resin from the alkaline aqueous effluent of shellac manufacturing industry. The recovered lac resin has been characterized by 13C-NMR, FT-IR and melting point and the data were compared with standard industrial-grade resin. The recovered lac resin was evaluated by the lac manufacturing industry for commercial applications.

The application of dry garlic powder and humic feed additive Humiton to increase the efficiency of sturgeons stock material growing in aquaculture

Restoring the population of relic fish sturgeons is a priority for international environmental protection measures. This problem is solved by mass production of fish fries in aquaculture for natural water bodies stocking. In this regard the effective technologies of production of such material is elevant. For this purpose the feeds for fries growing are enriches with additives of natural origin, which increase the viability and productivity of objects and have no negative impact on product quality and environment. As such additives, preparations based on food and medicinal plants — phytobiotics, as well as complex natural organic molecules — humic substances are used. In this experiment, Siberian sturgeon (Acipenser baerii Brandt, 1869) fries with an initial weight of 153.8±14.3 mg were fed with standard feed enriched with various doses of dry garlic powder as phytobiotic and humic feed additive Humiton. The inclusion of garlic powder at a dose of 30 g/kg and Humiton at the rate of 1 g/kg of humic acids to feed composition significantly increased the efficiency of fish rearing. After 5 weeks of experiment the survive of objects exceeded the control by 9.9%; the mass of fries was higher by 77.6% against the control and by 50% higher than the value of the calculated indicator of the factory juvenile sturgeons mass intended for stocking. The result obtained makes it possible to increase the efficiency of growing sturgeon fries in aquaculture in order to increase the mass and viability of the fish stock.

Ultrastable Bioderived Organic Anode Induced by Synergistic Coupling of Binder/Carbon-Network for Advanced Potassium-Ion Storage.

Bioderived molecules have been identified as viable anodes for organic potassium-ion batteries (OPIBs) due to the abundance of the necessary natural resources, their high capacity, and their sustainability. However, the high solubility and the inherent nonconductivity cause serious capacity decay and large voltage hysteresis. Here, the biomass molecule juglone was cross-linked with a carbon nanotube network, coupling and cooperating with sodium alginate binder (J@CNT-SA), and was proposed to inhibit small molecule dissolution via weak intermolecular interactions. The synergistic effect of hydrogen bonding and π-π stacking is proven for its outstanding reversible high capacities (262 mA h g-1 at 0.05 A g-1), and a remarkable long life span with capacity retention of 77% over 5000 cycles. Further in situ Fourier transform infrared spectroscopy (FTIR) was performed to reveal the electrochemical mechanism. The feasibility of juglone as an anode for PIBs paves the way for other natural organic small molecules to be investigated as potential energy storage materials.

Discovery of Polar Ozonation Byproducts via Direct Injection of Effluent Organic Matter with Online LC-FT-ICR-MS.

Effluent organic matter (EfOM), a major ozone consumer during wastewater ozonation, is a complex mixture of natural and anthropogenic organic molecules. Ozonation of EfOM adds to molecular complexity by introducing polar and potentially mobile ozonation byproducts (OBPs). Currently, nontargeted direct infusion (DI) ultrahigh resolution mass spectrometry (e.g. FT-ICR-MS) is used to study OBPs but requires sample extraction, limiting the accessible polarity range of OBPs. To better understand the impact of ozonation on EfOM and the formation of polar OBPs, nonextracted effluent was analyzed by direct injection onto a reversed-phase liquid chromatography system (RP-LC) online hyphenated with an FT-ICR-MS. Over four times more OBPs were detected in nonextracted EfOM compared to effluent extracted with solid phase extraction and measured with DI-FT-ICR-MS (13817 vs 3075). Over 1500 highly oxygenated OBPs were detected exclusively in early eluting fractions of nonextracted EfOM, indicating polar OBPs. Oxygenation of these newly discovered OBPs is higher than previously found, with an average molecular DBE-O value of -3.3 and O/C ratio of 0.84 in the earliest eluting OBP fractions. These polar OBPs are consistently lost during extraction but may play an important role in understanding the environmental impact of ozonated EfOM. Moreover, 316 molecular formulas classified as nonreactive to ozone in DI-FT-ICR-MS can be identified with LC-FT-ICR-MS as isomers with varying degrees of reactivity, providing for the first time experimental evidence of differential reactivity of complex organic matter isomers with ozone.

The synthesis of a nanodrug using metal-based nanozymes conjugated with ginsenoside Rg3 for pancreatic cancer therapy.

Nanozymes have limited applications in clinical practice due to issues relating to their safety, stability, biocompatibility, and relatively low catalytic activity in the tumor microenvironment (TME) in vivo. Herein, we report a synergistic enhancement strategy involving the conjugation of metal-based nanozymes (Fe@Fe3O4) with natural bioactive organic molecules (ginsenoside Rg3) to establish a new nanodrug. Importantly, this metal–organic nanocomposite drug ensured the stability and biosafety of the nanozyme cores and the cellular uptake efficiency of the whole nanodrug entity. This nanodrug is based on integrating the biological characteristics and intrinsic physicochemical properties of bionics. The glycoside chain of Rg3 forms a hydrophilic layer on the outermost layer of the nanodrug to improve the biocompatibility and pharmacokinetics. Additionally, Rg3 can activate apoptosis and optimize the activity and status of normal cells. Internal nanozymes enter the TME and release Fe3+ and Fe2+, and the central metal Fe(0) continuously generates highly active Fe2+ under the conditions of the TME and in the presence of Fe3+, maintaining the catalytic activity. Therefore, these nanozymes can effectively produce reactive oxygen species and oxygen in the TME, thereby promoting the apoptosis of cancer cells. Thus, we propose the use of a new type of metal–organic nanocomposite material as a synergistic strategy against cancer.

A resorufin-based fluorescence probe for visualizing biogenic amines in cells and zebrafish.

Biogenic amines (BAs) are a family of nitrogen-bearing natural organic molecules with at least one primary amine, which play an important role in living organisms. Elevated concentration of BAs may cause neuron disorder, Parkinson's disease and many other diseases. Therefore, it is essential to monitor BAs in living organisms. Herein, we reported a resorufin-based fluorescence probe for sensing of various BAs. Upon nucleophilic substitution reaction with BAs, the probe released resorufin, affording to strong fluorescence emission at 592 nm with rapid response (<8 min), good selectivity and a low detection limit (LOD = 0.47 μM). The probe has low cytotoxicity and good membrane permeability, and has been successfully used to visualize BAs in living cells and zebrafish with good performance.

Pharmacological activities and toxicities of alkaloids on human health

Alkaloids are a huge class of natural occurring organic molecules, which contain nitrogen atom or atoms (amino or amido in some cases) in their structures. Alkaloids are extremely divergent chemical structures including heterocyclic ring systems and encompass more than 20,000 different molecules in organisms. They are present not only in human daily life, in food and drinks but also as stimulant drugs, medicines, narcotics, insecticides and in many physiological activities. They showed strong biological effects on animal and human organisms even in very small doses. Alkaloids show several pharmacological activities on human healthsuch as anti-cancer, anti-inflammatory, Anti-malarial, Anti-microbial, Anti-hypertensive, Anti-diabetic, Anti-oxidant. Alkaloids directly act on the central nervous system in the human body and also affect nucleic acid, DNA (Deoxy Ribonucleic acid), RNA (Ribonucleic acid), membrane permeability and proteins. In this review article we aimed to investigate the pharmacological activities of different alkaloids, their importance in medicinal science and their toxicity on human health.