Impact of organic matter molecular weight on hexavalent chromium enrichment in green microalgae.

In lightly polluted water containing heavy metals, organic matter, and green microalgae, the molecular weight of organic matter may influence both the growth of green microalgae and the concentration of heavy metals. This study elucidates the effects and mechanisms by which different molecular weight fractions of fulvic acid (FA), a model dissolved organic matter component, facilitate the bioaccumulation of hexavalent chromium (Cr(VI)) in a typical green alga, Chlorella vulgaris. Findings show that the addition of FA fractions with molecular weights greater than 10 kDa significantly enhances the enrichment of total chromium and Cr(VI) in algal cells, reaching 21.58%-31.09 % and 16.17 %-22.63 %, respectively. Conversely, the efficiency of chromium enrichment in algal cells was found to decrease with decreasing molecular weight of FA. FA molecular weight within the range of 0.22 µm-30 kDa facilitated chromium enrichment primarily through the algal organic matter (AOM) pathway, with minor contributions from the algal cell proliferation and extracellular polymeric substances (EPS) pathways. However, with decreasing FA molecular weight, the AOM and EPS pathways become less prominent, whereas the algal cell proliferation pathway becomes dominant. These findings provide new insights into the mechanism of chromium enrichment in green algae enhanced by medium molecular weight FA.

Cr(VI) Reduction and Sequestration by FeS Nanoparticles Formed in situ as Aquifer Material Coating to Create a Regenerable Reactive Zone.

Remediation of large and dilute plumes of groundwater contaminated by oxidized pollutants such as chromate is a common and difficult challenge. Herein, we show that in situ formation of FeS nanoparticles (using dissolved Fe(II), S(-II), and natural organic matter as a nucleating template) results in uniform coating of aquifer material to create a regenerable reactive zone that mitigates Cr(VI) migration. Flow-through columns packed with quartz sand are amended first with an Fe2+ solution and then with a HS- solution to form a nano-FeS coating on the sand, which does not hinder permeability. This nano-FeS coating effectively reduces and immobilizes Cr(VI), forming Fe(III)-Cr(III) coprecipitates with negligible detachment from the sand grains. Preconditioning the sand with humic or fulvic acid (used as model natural organic matter (NOM)) further enhances Cr(VI) sequestration, as NOM provides additional binding sites of Fe2+ and mediates both nucleation and growth of FeS nanoparticles, as verified with spectroscopic and microscopic evidence. Reactivity can be easily replenished by repeating the procedures used to form the reactive coating. These findings demonstrate that such enhancement of attenuation capacity can be an effective option to mitigate Cr(VI) plume migration and exposure, particularly when tackling contaminant rebound post source remediation.

Synthetic musks in the natural environment: Sources, occurrence, concentration, and fate-A review of recent developments (2010-2023).

Synthetic musks (SMs) have served as cost-effective substitutes for natural musk compounds in personal care and daily chemical products for decades. Their widespread use has led to their detection in various environmental matrices, raising concerns about potential risks. Despite numerous studies on SM levels in different natural environments, a systematic review of their contemporary presence is lacking. This review aims to address this gap by summarising recent research developments on SMs in diverse natural environments, including river water, lake water, seawater, estuarine water, groundwater, snow, meltwater, sediments, aquatic suspended matter, soils, sands, outdoor air, and atmospheric particulate matter. Covering the period from 2010 to 2023, the review focuses on four SM categories: nitro, polycyclic, macrocyclic, and alicyclic. It systematically examines their sources, occurrences, concentrations, spatial and temporal variations, and fate. The literature reveals widespread detection of SMs in the natural environment (freshwater and sediments in particular), with polycyclic musks being the most studied group. Both direct (e.g., wastewater discharges) and indirect (e.g., human recreational activities) sources contribute to SM presence. Levels of SMs vary greatly among studies with higher levels observed in certain regions, such as sediments in Southeast Asia. Spatial and temporal variations are also evident. The fate of SMs in the environment depends on their physicochemical properties and environmental processes, including bioaccumulation, biodegradation, photodegradation, adsorption, phase exchange, hydro-dilution effects. Biodegradation and photodegradation can decrease SM levels, but may produce more persistent and eco-toxic products. Modelling approaches have been employed to analyse SM fate, especially for indirect processes like photodegradation or long-distance atmospheric transport. Future studies should further investigate the complex fate if SMs and their environmental influence. This review enhances understanding of SM status in the natural environment and supports efforts to control environmental contamination.

Phanogracilins A-C, New Bibenzochromenones of Crinoid Phanogenia gracilis (Hartlaub, 1890).

Three new bibenzochromenones named phanogracilins A-C (1-3) were isolated from the crinoid Phanogenia gracilis. The structure of 1 was established using X-ray crystallography as 5,5',6,6',8,8'-hexahydroxy-2,2'-dipropyl-4H,4'H-[7,9'-bibenzo[g]chromene]-4,4'-dione. This allowed us to assign reliably 2D NMR signals for compound 1 and subsequently for its isomer 2 that differed in the connecting position of two benzochromenone moieties (7,10' instead of 7,9'), and compound for 3 that differed in the length of the aliphatic chain of one of the fragments. Compound 4 was derived from 1 in alkaline conditions, and its structure was elucidated as 5,5',6',8,8'-pentahydroxy-2,2'-dipropyl-4H,4'H-[7,9'-bibenzo[g]chromene]-4,4',6,9-tetraone. Even though compounds 1-4 did not contain stereo centers, they possessed notable optical activity due to sterical hindrances, which limited the internal rotation of two benzochromenone fragments around C(7)-C(9'/10') bonds. Isolated bibenzochromenones 1-4 were tested for their antiradical, neuroprotective and antimicrobial activities. Compounds 1, 3 and 4 demonstrated significant antiradical properties towards ABTS radicals higher than the positive control trolox. Compounds 1 and 4 exhibited moderate neuroprotective activity, increasing the viability of rotenone-treated Neuro-2a cells at a concentration of 1 µM by 9.8% and 11.8%, respectively. Compounds 1 and 3 at concentrations from 25 to 100 µM dose-dependently inhibited the growth of Gram-positive bacteria S. aureus and yeast-like fungi C. albicans, and they also prevented the formation of their biofilms. Compounds 2 and 4 exhibited low antimicrobial activity.

Spiropyran-Based Photoisomerizable α-Amino Acid for Membrane-Active Peptide Modification.

Photoisomerizable peptides are promising drug candidates in photopharmacology. While azobenzene- and diarylethene-containing photoisomerizable peptides have already demonstrated their potential in this regard, reports on the use of spiropyrans to photoregulate bioactive peptides are still scarce. This work focuses on the design and synthesis of a spiropyran-derived amino acid, (S)-2-amino-3-(6'-methoxy-1',3',3'-trimethylspiro-[2H-1-benzopyran-2,2'-indolin-6-yl])propanoic acid, which is suitable for the preparation of photoisomerizable peptides. The utility of this amino acid is demonstrated by incorporating it into the backbone of BP100, a known membrane-active peptide, and by examining the photoregulation of the membrane perturbation by the spiropyran-containing peptides. The toxicity of the peptides (against the plant cell line BY-2), their bacteriotoxicity (E. coli), and actin-auxin oscillator modulation ability were shown to be significantly dependent on the photoisomeric state of the spiropyran unit.

Effect of Maillard reaction based on catechol polymerization on the conversion of food waste to humus.

The pollution and harm of food waste (FW) are increasingly concerned, which has the dual attributes of pollutants and resources. This study aimed to improve the synthesis efficiency of FW humic substances (HS), and investigating the effect of catechol on the formation mechanism and structure of humic acid (HA) and fulvic acid (FA). Results indicated that catechol incorporation could enable to exhibit higher HS yield and more complex structure, especially the maximum particle size of FA reached 4800 nm. This was due to the combination of catechol with multiple nitrogenous compounds, which accelerated molecular condensation. Spectroscopic scans analysis revealed that Maillard reaction occurs first. Subsequently, Maillard reaction products and amino acids were combined with different sites of catechol, which leads to the difference of molecular structure of HS. The structure of FA is characterized by an abundance of carboxyl and hydroxyl groups, whereas HA is rich in benzene and heterocyclic structures. The structural difference was responsible for the disparity in the functional properties of FA and HA. Specifically, the presence of amino, hydroxyl, pyridine, and carboxyl groups in FA contributes significantly to its chelating activity. This research provides an efficient and sustainable unique solution for the high-value of FW conversion, and provides evidence for understanding the structural evolution of HA and FA.

Benzopyran hydrazones with dual PPARα/γ or PPARα/δ agonism and an anti-inflammatory effect on human THP-1 macrophages.

Peroxisome proliferator-activated receptors (PPARs) play a major role in regulating inflammatory processes, and dual or pan-PPAR agonists with PPARγ partial activation have been recognised to be useful to manage both metabolic syndrome and metabolic dysfunction-associated fatty liver disease (MAFLD). Previous works have demonstrated the capacity of 2-prenylated benzopyrans as PPAR ligands. Herein, we have replaced the isoprenoid bond by hydrazone, a highly attractive functional group in medicinal chemistry. In an attempt to discover novel and safety PPAR activators, we efficiently prepared benzopyran hydrazone/hydrazine derivatives containing benzothiazole (series 1) or 5-chloro-3-(trifluoromethyl)-2-pyridine moiety (series 2) with a 3- or 7-carbon side chain at the 2-position of the benzopyran nucleus. Benzopyran hydrazones 4 and 5 showed dual hPPARα/γ agonism, while hydrazone 14 exerted dual hPPARα/δ agonism. These three hydrazones greatly attenuated inflammatory markers such as IL-6 and MCP-1 on the THP-1 macrophages via NF-κB activation. Therefore, we have discovered novel hits (4, 5 and 14), containing a hydrazone framework with dual PPARα/γ or PPARα/δ partial agonism, depending on the length of the side chain. Benzopyran hydrazones emerge as potential lead compounds which could be useful for treating metabolic diseases.

Isocyanide-based multicomponent reactions for the synthesis of benzopyran derivatives with biological scaffolds.

Benzopyrans (BZPs) are among the most privileged and influential small O-heterocycles that form the core of many natural compounds, commercial drugs, biological compositions, agrochemicals, and functional materials. BZPs are divided into six general categories including coumarins, chromans, 2H-chromenes, 4H-chromenes, chromones, and 4-chromanones, each of which is abundant in many plants and foods. These oxygenated heterocyclic compounds are fascinating motifs and have extensive applications in biology and materials science. Hence, numerous efforts have been made to develop innovative approaches for their extraction and synthesis. However, most of them are step-by-step or multi-step strategies that suffer from waste material generation and a tedious extraction process. Isocyanide-based multicomponent reactions (I-MCRs) offer a highly efficient method for overcoming these problems. The I-MCR is a simple and environmentally friendly one-pot domino procedure that does not require intermediate isolation or workup and is generally more efficient in material usage. This review covers all research articles related to I-MCRs for synthesizing BZP derivatives from the beginning to the middle of the year 2023. This strategy will be useful for organic and pharmaceutical chemists to design new drugs and optimize the synthesis steps of biological compounds and commercial drugs with benzopyran cores.

Evolution from basic to advanced structure of fulvic acid and humic acid prepared by food waste.

Fulvic acid (FA) and humic acid (HA) are common polyacids in nature. However, the evolutionary process of their basic and advanced structures is still unclear. FA and HA were separated into five molecular weight components to investigate the process of evolution from small to large molecules. The primary structure analysis showed that FA were rich in CN, COOH and OH content, while HA were rich in (CH2)n, NH2 and CC. Moreover, with the molecular weight increasing, the structures could complement each other to maintain the hydrophilic or hydrophobic balance. The 2D-COS spectroscopy demonstrated that during the growth of FA, COOH, NH2 and OH firstly respond. On the other hand, during the growth of HA, NH2 and (CH2)n firstly respond. In addition, advanced structure of FA was affected by intramolecular hydrogen bonds and π - π interaction. HA was affected by hydrophobic interactions due to the abundance of hydrophobic groups, primarily (CH2)n and benzene rings. 3D conformational fitting and particle size characterization confirmed that the interaction forces determine that FA and HA become tightly and loosely molecules respectively. This study is to further explore the geochemical formation and evolution process of FA and HA molecules.

Design, synthesis of novel chromene-based scaffolds targeting hepatocellular carcinoma: Cell cycle arrest, cytotoxic effect against resistant cancer cells, apoptosis induction, and c-Src inhibition.

New chromene derivatives were synthesized based on 4-(3,4-dimethoxy)-4H-chromene scaffold. All target compounds exhibited cytotoxic activity against HepG2 cells (IC50 = 2.40-141.22 µM). Chromens 5 and 9 showed superior cytotoxicity over staurosporine (IC50 = 18.27 µM) and vinblastine (IC50 = 5.20 µM). c-Src kinase inhibition assay of compounds 5 and 9 displayed the dominant c-Src inhibitory activity of 5 (IC50 = 0.184 µM) over 9 (IC50 = 0.288 µM). The safety of the most potent compound 5 against normal WI-38 cells was confirmed via its IC50 of 115.75 µM comparable with 5-FU (IC50 = 16.28 µM). Moreover, the promising chromene 5 displayed potent cytotoxicity against resistant HepG2 cells with IC50 of 26.03 µM comparable with 5-FU (IC50 = 42.68 µM). The most active chromene 5 arrested the HepG2 cell cycle at the S phase and induced a 29-fold increase in the total number of apoptotic cells indicating pre-G1 apoptosis. The ability of compound 5 to induce apoptosis was supported via elevation of caspase-3, caspase-7, caspase-9 and proapoptotic Bax protein levels in addition to downregulation of the antiapoptotic Bcl2 protein. Molecular docking studies of compound 5 showed good binding interaction pattern inside c-Src kinase enzyme active site.

Synthesis and biological evaluations of 8-biaryl-2,2-dimethylbenzopyranamide derivatives against Alzheimer's disease and ischemic stroke.

Alzheimer's disease, the commonest cause of dementia, is a growing global health concern with huge implications for individuals and society. Stroke has still been a significant challenge in clinics for a long time, which is the second leading cause of death in the world, especially ischemic stroke. Both Alzheimer's disease and stroke are closely related to oxidative stress and HIF-1 signaling pathways in nerve cells. Herein, we describe our structure-based design, synthesis, and biological evaluation of a new class of 8-biaryl-2,2-dimethylbenzopyranamide derivatives as natural product derivatives. Our efforts have resulted in the discovery of highly potent neuroprotective agents, as exemplified by compound D13 as a HIF-1α inhibitor, which significant improvement in the behavior of Alzheimer's disease mice and shows great potential improvement of brain infarct volume in pMCAO model rats, improves the increase of blood-brain barrier permeability after cerebral ischemia in rats, neuroprotective effect, reduce the level of apoptotic cells in rats after cerebral ischemia, better than Edaravone.

Synthesis and Characterization of a New Class of Chromene-Azo Sulfonamide Hybrids as Promising Anticancer Candidates with the Exploration of Their EGFR, hCAII, and MMP-2 Inhibitors Based on Molecular Docking Assays.

In this study, novel selective antitumor compounds were synthesized based on their fundamental pharmacophoric prerequisites associated with EGFR inhibitors. A molecular hybridization approach was employed to design and prepare a range of 4H-chromene-3-carboxylates 7a-g, 8, and 11a-e derivatives, each incorporating a sulfonamide moiety. The structures of these hybrid molecules were verified using comprehensive analytical and spectroscopic techniques. During the assessment of the newly synthesized compounds for their anticancer properties against three tumor cell lines (HepG-2, MCF-7, and HCT-116), compounds 7f and 7g displayed remarkable antitumor activity against all tested cell lines, outperforming the reference drug Cisplatin in terms of efficacy. Consequently, these promising candidates were selected for further investigation of their anti-EGFR, hCAII, and MMP-2 potential, which exhibited remarkable effectiveness against EGFR and MMP2 when compared to Sorafenib. Additionally, docking investigations regarding the EGFR binding site were implemented for the targeted derivatives in order to attain better comprehension with respect to the pattern in which binding mechanics occur between the investigated molecules and the active site, which illustrated a higher binding efficacy in comparison with Sorafenib.

Synthesis of 3-sulfenylindole derivatives from 4-hydroxy-2H-chromene-2-thione and indole using oxidative cross-dehydrogenative coupling reaction and anti-proliferative activity study of some of their sulfone derivatives.

The synthesis of hitherto unreported 3-sulfenylindole derivatives is achieved from 4-hydroxy-2H-chromene-2-thione (1) and indole (2) by employing an oxidative cross-dehydrogenative coupling reaction using a combination of 10 mol% of molecular iodine and 1 equivalent of TBHP in DMSO at room temperature. Then, the 3-sulfenylindole derivatives 3a, 3b, 3d, 3f, 3 h, and 3 k were converted into their corresponding sulfone derivatives because of lead likeness properties. Subsequently, a target prediction and docking study of six sulfone derivatives (5a-f) was performed, and four sulfones, namely 5a, 5d, 5e, and 5f, were selected for further in-vitro studies. The four sulfones mentioned above exhibited prominent anti-proliferative activity on breast cancer (MCF7) cell lines. In addition, this reaction was exergonic through quantum chemical analysis of the mechanistic steps. The salient features of this reaction are mild reaction conditions, good yields, and broad substrate scope.

Molecular design and synthesis of methoxy-substitued spiropyrans with photomodulated NIR-fluorescence.

This study focuses on the molecular design and synthesis of salt spiropyrans with near-IR fluorescence. The structure of the obtained compounds was confirmed by NMR, IR and mass spectroscopy. In the course of studying the spectral and photoluminescent characteristics, it was possible to reveal the effect of some substituents in various positions on the properties of spiropyran dyes. Due to the structural similarity of one of the isomers to cyanine dyes, the obtained compounds are of interest as potential fluorescent probes for bioimagimg, in particular, for DNA studies. To reveal their ability of binding to DNA molecules molecular docking was carried out. Toxic effects of compounds demonstrating NIR fluorescence were studied on biofilms, as well as using bacterial lux-biosensors.

Light-Modulated Morphological Transformation of Spiropyran Derivative from Nanosphere to Nanorod.

The construction of tunable morphological systems has important implications for understanding the mechanism of molecular self-assembly. In this study, a spiropyran derivative M1 is reported with light-responsive assembly morphology, which can be tuned from nanosphere to nanorod by ultraviolet light irradiation. The absorption spectra show that M1 molecules are transformed from closed-ring (SP) isomers into open-ring (MC) isomers and start to form H-aggregates with increasing irradiation time. Density functional theory calculations indicate that MC-MC isomers possess stronger binding energy than SP-SP isomers. The MC isomers may thus facilitate the dissociation of the SP-SP aggregates and promote the change of self-assembled morphology with the aid of stronger π-π stackings and dipole-dipole interactions. The research gives an effective method for modulating the morphology of assemblies, with great potential for applications in smart materials.

Rigidity and Flexibility: Unraveling the Role of Fulvic Acid in Uranyl Sorption on Graphene Oxide Using Molecular Dynamics Simulations.

Using molecular dynamics simulations, this work targets a molecular understanding on the rigidity and flexibility of fulvic acid (FA) in uranyl sorption on graphene oxide (GO). The simulations demonstrated that both rigid Wang's FA (WFA) and flexible Suwannee River FA (SRFA) can provide multiple sites to cooperate with GO for uranyl sorption and act as "bridges" to connect uranyl and GO to form GO-FA-U (type B) ternary surface complexes. The presence of flexible SRFA was more beneficial to uranyl sorption on GO. The interactions of WFA and SRFA with uranyl were primarily driven by electrostatics, and the electrostatic interaction of SRFA-uranyl was significantly stronger owing to the formation of more complexes. The flexible SRFA could markedly enhance the bonding strength of uranyl with GO by folding itself to provide more sites to coordinate with uranyl. The rigid WFAs tended to be adsorbed on the GO surface in parallel due to π-π interactions, whereas the flexible SRFAs took more slant configurations resulting from intermolecular hydrogen bonds. This work provides new insights into the sorption dynamics, structure, and mechanism and addresses the effect of molecular rigidity and flexibility, with great significance for FA-based remediation strategies of uranium-contaminated sites.

Simple Strategy for Benzo[g]chromene Synthesis via a Photochemical Intramolecular Cyclization Reaction.

Photochemical reactions are often a desirable strategy for organic synthesis because they do not require toxic and expensive reagents and produce less waste than thermal reactions. Herein, a facile photochemical strategy is described to synthesize benzo[g]chromene derivatives. This strategy utilizes the photoredox reaction of quinones, which allows C-H bond oxidation in the vicinity of the photoexcited quinone carbonyl group. The reaction mechanism was investigated using 1H NMR analysis. The intramolecular cyclization reaction proceeded via the formation of 1,3-dioxole compounds as intermediates by the photoredox reaction of p-quinone, followed by re-cyclization. The synthesized benzo[g]chromene derivatives are important heterocyclic skeletons with useful biological and pharmacological properties.

Enhanced degradation of few-layer black phosphorus by fulvic acid: Processes and mechanisms.

The oxidation of the emerging nanomaterial black phosphorus (BP) affected by pH and oxygen has been carefully documented. However, in natural waters, there is a large amount of chemically reactive organic matters like fulvic acid (FA), whose impacts on degradation and stability of few-layer BP or BP nanosheets (BPNS) are scarcely disclosed. Hence, we investigated the kinetics of BPNS degradation products (H2PO2-, HPO32-, and PO43-) in the presence of FA. The results showed that the apparent reaction rate constants of BPNS were 0.026, 0.050, and 0.060 d-1 under oxygen-and-light condition and 0.005, 0.016, and 0.023 d-1 under hypoxia-and-darkness condition at FA gradients of 0, 2.5, and 5 mgC/L, respectively. Microscopic observations, simple molecular simulation experiment, and density functional theory computation explained that FA significantly enhanced the degradation of P atoms on the BPNS surface through the indirect pathway of reducing the energy barrier of O2 dissociative adsorption and the direct pathway of chemical adsorption, which caused the P-P bond on the BPNS surface to break down and formed P-O bonds or C-P bonds. This study revealed for the first time the degradation mechanism of BPNS in the presence of FA, which is a chemical mechanism of the BPNS transformation behavior. It helps to make a more scientific risk assessment of BP in natural waters.

Isolation of new compounds related to xyloketals biosynthesis implies an alternative pathway for furan-fused-chromene formation.

In fungi, there is a rare group of natural products harboring the 2,3,3a,9a-tetrahydro-4H-furo[2,3-b]chromene skeleton, represented by xyloketal B, which display a wide range of biological activities and have drawn significant attention. In this work, four new analogues simpliketals A-D (1-4), as well as two other new compounds simplilactones A and B (5 and 6), were isolated from Simplicillium sp. AHK071-01. Their structures were elucidated by extensive NMR spectroscopic methods, 13C NMR calculation, single-crystal X-ray diffraction, and ECD calculation. In addition, five known compounds (7-11) including alboatrin (7) were also obtained. Based on the structural similarity of the above compounds, we inferred that compounds 5, 6, and 8-11 might be biosynthetically related with 1-4 and 7, which allowed us to propose an alternative biosynthetic route to generate the furan-fused chromene skeleton of this class of compounds, instead of a previously presumed polyketide-terpenoid hybrid pathway. Finally, cytotoxicity assays showed that 1-4 exhibited weak inhibitory activity on PANC-1 cells and that 2 and 3 possessed moderate activity against SH-SY5Y cells.