A newly identified algicidal bacterium of Pseudomonas fragi YB2: Algicidal compounds and effects.

Harmful algal bloom (HAB) is an unresolved existing problem worldwide. Here, we reported a novel algicidal bacterium, Pseudomonas fragi YB2, capable of lysing multiple algal species. To Chlorella vulgaris, YB2 exhibited a maximum algicidal rate of 95.02 % at 120 h. The uniqueness of YB2 lies in its ability to self-produce three algicidal compounds: 2-methyl-1, 3-cyclohexanedione (2-MECHD), N-phenyl-2-naphthylamine, and cyclo (Pro-Leu). The algicidal properties of 2-MECHD have not been previously reported. YB2 significantly affected the chloroplast and mitochondrion, thus decreasing in chlorophyll a by 4.74 times for 120 h and succinate dehydrogenase activity by 103 times for 36 h. These physiological damages disrupted reactive oxygen species and Ca2+ homeostasis at the cellular level, increasing cytosolic superoxide dismutase (23 %), catalase (35 %), and Ca2+ influx. Additionally, the disruption of Ca2+ homeostasis rarely reported in algicidal bacteria-algae interaction was observed using the non-invasive micro-test technology. We proposed a putative algicidal mechanism based on the algicidal outcomes and physiological algicidal effects and explored the potential of YB2 through an algicidal simulation test. Overall, this study is the first to report the algicidal bacterium P. fragi and identify a novel algicidal compound, 2-MECHD, providing new insights and a potent microbial resource for the biocontrol of HAB.

Electrocatalytic coupled biofilter for treating cyclohexanone-containing wastewater: Degradation, mechanism and optimization.

Electrocatalytic coupled biofilter (EBF) technology organically integrates the characteristics of electrochemistry and microbial redox, providing ideas for effectively improving biological treatment performance. In this study, an EBF system was developed for enhanced degradation of cyclohexanone in contaminated water. Experimental results show that the system can effectively remove cyclohexanone in contaminated water. Under the optimal parameters, the removal rates of cyclohexanone, TP, NH4+-N and TN were 97.61 ± 1.31%, 76.31 ± 1.67%, 94.14 ± 2.13% and 95.87 ± 1.01% respectively. Degradation kinetics studies found that electrolysis, adsorption, and biodegradation pathways play a major role in the degradation of cyclohexanone. Microbial community analysis indicates that voltage can affect the structure of the microbial community, with the dominant genera shifting from Acidovorax (0 V) to Brevundimonas (0.7 V). Additionally, Acidovorax, Cupriavidus, Ralstonia, and Hydrogenophaga have high abundance in the biofilm and can effectively metabolize cyclohexanone and its intermediates, facilitating the removal of cyclohexanone. In summary, this research can guide the development and construction of highly stable EBF systems and is expected to be used for advanced treatment of industrial wastewater containing cyclohexanone.

[Development of Organocatalytic Reactions for the Synthesis of Natural Products and Pharmaceuticals].

This review describes novel organocatalytic methods for the enantioselective construction of spiroindans and spirochromans and the application of the methods to the total synthesis of natural products. We developed an intramolecular Friedel-Craftstype 1,4-addition in which the substrates were a resorcinol derivative and 2-cyclohexenone linked by an alkyl chain. The reaction proceeded smoothly in the presence of a cinchonidine-based primary amine (30 mol%) with water and p-bromophenol as additives. A variety of spiroindanes were obtained with high enantioselectivity under these conditions. The reaction was applied in the first total synthesis of the unusual proaporphine alkaloid (-)-misramine, which included the key steps of enantioselective spirocyclization and double reductive amination of the keto-aldehyde to form a piperidine ring toward the end of the synthesis. The total synthesis of misrametine was achieved by selective demethylation of the methoxy group from the precursor to misramine. Next, a method for highly enantioselective organocatalytic construction of spirochromans containing a tetrasubstituted stereocenter was developed. An intramolecular oxy-Michael addition was catalyzed by a bifunctional cinchona alkaloid thiourea catalyst. A variety of spirochroman compounds containing a tetrasubstituted stereocenter were obtained with excellent enantioselectivity of up to 99% enantiomeric excess. The reaction was applied to the asymmetric formal synthesis of (-)-(R)-cordiachromene.

Characterization, DFT study and evaluation of antioxidant potentials of mycosporine-like amino acids (MAAs) in the cyanobacterium Anabaenopsis circularis HKAR-22.

The physiological parameters such as growth, Chl a content, and photosynthetic performance of the experimental cyanobacterium Anabaenopsis circularis HKAR-22 were estimated to evaluate the cumulative effects of photosynthetically active radiation (PAR) and ultraviolet (UV) radiation. Maximum induction of UV-screening molecules, MAAs, was observed under the treatment condition of PAR + UV-A + UV-B (PAB) radiations. UV/VIS absorption spectroscopy and HPLC-PDA detection primarily confirmed the presence of MAA-shinorine (SN) having absorption maxima (λmax) at 332.3 nm and retention time (RT) of 1.47 min. For further validation of the presence of SN, HRMS, FTIR and NMR were utilized. UV-stress elevated the in vivo ROS scavenging and in vitro enzymatic antioxidant capabilities. SN exhibited substantial and concentration-dependent antioxidant capabilities which was determined utilizing 2,2-diphenyl-1-picryl-hydrazyl (DPPH), 2,2'-azinobis-(3-ethylbenzothiazoline-6-sulfonate (ABTS), ferric reducing power (FRAP) and superoxide radical scavenging assay (SRSA). The density functional theory (DFT) method using B3LYP energy model and 6-311G++(d,p) basis set was implied to perform the quantum chemical calculation to systematically investigate the antioxidant nature of SN. The principal pathways involved in the antioxidant reactions along with the basic molecular descriptors affecting the antioxidant potentials of a compound were also studied. The results favor the potential of SN as an active ingredient to be used in cosmeceutical formulations.

Novel pyrrolidine-alkylamino-substituted dicyanoisophorone derivatives as near-infrared fluorescence probe for imaging ß-amyloid in vitro and in vivo.

BACKGROUND: The formation of amyloid-ß (Aß) plaques is one of the key neuropathological hallmarks of Alzheimer's disease (AD). Near-infrared (NIR) probes show great potential for imaging of Aß plaques in vivo and in vitro. Dicyanoisophorone (DCIP) based Aß probes have attracted considerable attention due to their exceptional properties. However, DCIP probes still has some drawbacks, such as short emission wavelength (<650 nm) and low fluorescence intensity after binding to Aß. It is clear that further modification is needed to improve their luminescence efficiency and sensitivity. RESULTS: We designed and synthesize four novel pyrrolidine-alkylamino-substituted DCIP derivatives (6a-d) as imaging agents for ß-amyloid (Aß) aggregates. Compound 6c responds better to Aß aggregates than the other three compounds (6a, 6b and 6d) and its precursor DCIP. The calculated detection limit is to be as low as 0.23 µM. Compound 6c shows no cytotoxicity in the tested concentration for SH-SY5Y and HL-7702 cells. Additionally, compound 6c is successfully applied to monitor Aß aggregates in live SH-SY5Y cells and APP/PS1 transgenic mice. The retention time in the transgenic mice brain is much longer than that of age-matched wild-type mice. SIGNIFICANCE: The results indicates that compound 6c had an excellent ability to penetrate the blood-brain barrier and it could effectively distinguish APP/PS1 transgenic mice and wide-type mice. This represents its promising applications for Aß detection in basic and biomedical research.

Unraveling the interaction mechanism between orphan drug Nitisinone and bovine serum albumin through spectroscopic and in silico approaches.

The interaction between Nitisinone (NTBC) and bovine serum albumin (BSA) as the transport protein in a circulating system was investigated for the first time utilizing various analytical (UV-Vis spectrophotometry, fluorescence spectroscopy, dynamic light scattering, and differential scanning calorimetry) and computational (molecular docking and molecular dynamics simulations) methods. The BSA fluorescence intensity was quenched upon interaction with NTBC, and the quenching mechanism was observed as static. The interaction between NTBC and BSA was examined at 288 K, 298 K, and 308 K where the binding constants were found to be 1.44 × 105 ± 0.22 M-1, 5.18 × 104 ± 0.20 M-1, and 3.02 × 104 ± 0.22 M-1 respectively, suggesting an intermediate binding affinity between NTBC and BSA. Changes in the microenvironment surrounding tryptophan and tyrosine residues of BSA were elucidated using 3-D fluorescence spectroscopy. Thermodynamic studies revealed the calculated values of ΔH =  - 54.34 ± 5 kJ/mol and ΔS =  - 0.0908 ± 0.24 kJ/mol K-1, indicating the involvement of van der Waals forces and hydrogen bonds in the interaction between NTBC and BSA. Moreover, the interaction's spontaneous nature was evidenced by negative ΔG values across all temperatures. Using dynamic light scattering, it was observed that higher NTBC concentrations led to a gradual rise in hydrodynamic diameter and notable aggregation of the NTBC-BSA complex. Moreover, changing signal values and shifted peaks of BSA, NTBC, and complex in differential scanning calorimetry curves, meant there were molecular interactions between the NTBC and BSA. In silico approaches also elucidated how NTBC binds to active sites on BSA, further supporting other findings. Moreover, molecular docking studies offer a more profound insight into the changing dynamics of hydrophobic, hydrogen, and halogen bonding involved in stabilizing the NTBC-BSA complex.

Megastigmane glycosides from the traditional Uighur medicine Cydonia oblonga Mill.

Phytochemical investigation on the fruits of Cydonia oblonga Mill., a traditional Uighur medicine, led to the isolation of seven undescribed and nine known megastigmane glycosides. Their structures including absolute configurations were characterized by an extensive analysis of spectroscopic data including HRESIMS and NMR, combined with ECD calculations. Additionally, compounds 1, 2, 4, and 6-16 exhibited anti-inflammatory activity by inhibiting the secretion of cytokines TNF-α and IL-6 in RAW264.7 cells induced by lipopolysaccharides (LPS) with inhibitory rates of 10.79%-44.58% at 20 µM.

Sorption and mobility assessment of tembotrione in soils of upper, trans and middle Gangetic plain zones of India.

The presence of undesired agrochemicals residues in soil and water poses risks to both human health and the environment. The behavior of pesticides in soil depends both on the physico-chemical properties of pesticides and soil type. This study examined the adsorption-desorption and leaching behavior of the maize herbicide tembotrione in soils of the upper (UGPZ), trans (TGPZ) and middle Gangetic plain zones of India. Soil samples were extracted using acetone followed by partitioning with dichloromethane, whereas liquid-liquid extraction using dichloromethane was used for aqueous samples. Residues of tembotrione and its metabolite TCMBA, {2-chloro-4-(methylsulfonyl)-3-[(2,2,2-trifluoroethoxy) methyl] benzoic acid}, were quantified using liquid chromatography-tandem mass spectrometry. The data revealed that tembotrione adsorption decreased with increasing pH and dissolved organic matter but increased with salinity. The maximum adsorption occurred at pH 4, 0.01 m sodium citrate and 4 g/L NaCl, with corresponding Freundlich constants of 1.83, 2.28 and 3.32, respectively. The hysteresis index <1 indicated faster adsorption than desorption. Leaching studies under different flow conditions revealed least mobility in UGPZ soil and high mobility in TGPZ soil, consistent with groundwater ubiquity scores of 4.27 and 4.81, respectively. Soil amendments decreased tembotrione mobility in the order: unamended > wheat straw ash > wheat straw > farm yard manure > compost. The transformation of tembotrione to TCMBA and its mobility in soil columns were also assessed.

Design, Synthesis, and Biological Activity of Novel Triketone-Containing Phenoxy Nicotinyl Inhibitors of HPPD.

4-Hydroxyphenylpyruvate dioxygenase (HPPD) is a crucial target enzyme in albino herbicides. The inhibition of HPPD activity interferes with the synthesis of carotenoids, blocking photosynthesis and resulting in bleaching and necrosis. To develop herbicides with excellent activity, a series of 3-hydroxy-2-(6-substituted phenoxynicotinoyl)-2-cyclohexen-1-one derivatives were designed via active substructure combination. The title compounds were characterized via infrared spectroscopy, 1H and 13C nuclear magnetic resonance spectroscopies, and high-resolution mass spectrometry. The structure of compound III-17 was confirmed via single-crystal X-ray diffraction. Preliminary tests demonstrated that some compounds had good herbicidal activity. Crop safety tests revealed that compound III-29 was safer than the commercial herbicide mesotrione in wheat and peanuts. Moreover, the compound exhibited the highest inhibitory activity against Arabidopsis thaliana HPPD (AtHPPD), with a half-maximal inhibitory concentration of 0.19 µM, demonstrating superior activity compared with mesotrione (0.28 µM) in vitro. A three-dimensional quantitative structure-activity relationship study revealed that the introduction of smaller groups to the 5-position of cyclohexanedione and negative charges to the 3-position of the benzene ring enhanced the herbicidal activity. A molecular structure comparison demonstrated that compound III-29 was beneficial to plant absorption and conduction. Molecular docking and molecular dynamics simulations further verified the stability of the complex formed by compound III-29 and AtHPPD. Thus, this study may provide insights into the development of green and efficient herbicides.

A novel isophorone-based NIR fluorescent and colormetric probe for Al3+ sensing and its application for living cells and plants imaging.

In this paper, an isophorone-based NIR fluorescent and colormetric probe BDDH for Al3+ was synthesized and characterized, it showed highly selectivity and sensitivity through significant fluorescence enhancement and visible color change towards Al3+. The job plot confirmed that the binding ratio of BDDH with Al3+ was 1:1. Furthermore, the limit of detection (LOD) of Al3+ was determined to be 4.01 × 10-8 M. Moreover, BDDH was successfully applicated in identification of Al3+ in the different water samples, cell imaging in alive MCF-7 cells and plant imaging in soybean roots.

Crystal structure of HPPD inhibitor sensitive protein from Oryza sativa.

4-hydroxyphenylpyruvate dioxygenase (HPPD) Inhibitor Sensitive 1 (HIS1) is an endogenous gene of rice, conferring broad-spectrum resistance to ß-triketone herbicides. Similar genes, known as HIS1-like genes (HSLs), exhibit analogous functions and can complement the herbicide-resistant characteristics endowed by HIS1. The identification of HIS1 and HSLs represents a valuable asset, as the intentional pairing of herbicides with resistance genes emerges as an effective strategy for crop breeding. Encoded by HIS1 is a Fe(II)/2-oxoglutarate-dependent oxygenase responsible for detoxifying ß-triketone herbicides through hydroxylation. However, the precise structure supporting this function remains unclear. This work, which determined the crystal structure of HIS1, reveals a conserved core motif of Fe(II)/2-oxoglutarate-dependent oxygenase and pinpoints the crucial residue dictating substrate preference between HIS1 and HSL.

A Multicomponent Mannich Reaction Catalyzed by Hydrolases Immobilized on Titanate Nanotubes.

This study presents an innovative method for synthesizing ß-amino carbonylated compounds, specifically 2-[phenyl(phenylamino)methyl] cyclohexanone, achieving high conversions and diastereomeric ratios. Using trypsin or α-chymotrypsin in both free and immobilized forms on titanate nanotubes (NtsTi), synthesized through alkaline hydrothermal methods, successful immobilization yields were attained. Notably, α-chymotrypsin, when free, displayed a diastereoselective synthesis of the anti-isomer with 97 % conversion and 16 : 84 (syn : anti) diastereomeric ratio, which slightly decreased upon immobilization on NtsTi. Trypsin, in its free form, exhibited diastereoselective recognition of the syn-isomer, while immobilization on NtsTi (trypsin/NtsTi) led to an inversion of diastereomeric ratio. Both trypsin/NtsTi and α-chymotrypsin/NtsTi demonstrated significant catalytic efficiency over five cycles. In conclusion, NtsTi serves as an effective support for trypsin and α-chymotrypsin immobilization, presenting promising prospects for diastereoselective synthesis and potential industrial applications. Furthermore, it offers promising prospects for the diastereoselective synthesis of 2-[phenyl(phenylamino)methyl] cyclohexanone through multicomponent Mannich reaction and future industrial application.

Glutathione kinetically outcompetes reactions between dimedone and a cyclic sulfenamide or physiological sulfenic acids.

Dimedone and its derivates are used as selective probes for the nucleophilic detection of sulfenic acids in biological samples. Qualitative analyses suggested that dimedone also reacts with cyclic sulfenamides. Furthermore, under physiological conditions, dimedone must compete with the highly concentrated nucleophile glutathione. We therefore quantified the reaction kinetics for a cyclic sulfenamide model peptide and the sulfenic acids of glutathione and a model peroxiredoxin in the presence or absence of dimedone and glutathione. We show that the cyclic sulfenamide is stabilized at lower pH and that it reacts with dimedone. While reactions between dimedone and sulfenic acids or the cyclic sulfenamide have similar rate constants, glutathione kinetically outcompetes dimedone as a nucleophile by several orders of magnitude. Our comparative in vitro and intracellular analyses challenge the selectivity of dimedone. Consequently, the dimedone labeling of cysteinyl residues inside living cells points towards unidentified reaction pathways or unknown, kinetically competitive redox species.

Cyclohexenone Derivative and Drimane Sesquiterpenes from the Seagrass-Derived Fungus Aspergillus insuetus.

One new cyclohexenone derivative (1), and two undescribed drimane sesquiterpenes (2 and 3), together with another seven known drimane sesquiterpenes were isolated from a seagrass-derived fungus Aspergillus insuetus SYSU6925. Structures of these metabolites were elucidated by comprehensive spectroscopic analysis, including NMR analysis, mass spectrometry, and ECD calculations. Compounds 1-3, 5 and 7 displayed weak to moderate antifungal activities towards four phytopathogenic fungi, with Minimum inhibition concentration (MIC) values range from 50 to 200 µg/mL. Compound 1, a rare cyclohexenone derivative with n-propyl group exhibited more potent inhibitory activities (MIC, 50 µg/mL) against F. oxysporum than positive control (Triadimefon). Compounds 2 and 3 also exhibit potent anti-inflammatory activities by inhibiting the production of nitric oxide (NO) in RAW264.7 cells with IC50 values of 21.5±1.1 and 32.6±1.16 µM, respectively.

Dual Photochemical H-Atom Transfer and Cobalt Catalysis for the Desaturative Synthesis of Phenols from Cyclohexanones.

Phenols are integral aromatic molecules widely encountered in the structure of natural products and routinely utilised for the synthesis of high-value materials. Accessing highly substituted derivatives can often be difficult, especially when their functionalization pattern does not match the intrinsic reactivity leveraged by electrophilic aromatic substitution (SE Ar) chemistry. Here, we provide an alternative and mechanistically distinct approach for phenol synthesis using saturated cyclohexanone precursors. This process operates at ambient temperature, under simple purple light irradiation, and features a dual catalytic manifold carrying four sequential H-atom transfer processes.

Two ambuic acid dimers derived from homo-endo Diels-Alder reaction from Pestalotiopsis versicolor.

Two new dimers of ambuic acid, pestaloversicoloric acids A (1) and B (2), and a known derivative, 13(S)-hydroxyambuic acid (3), were isolated from the static fermentation product of Pestalotiopsis versicolor. The structural identification was accomplished via analyses on the data of HR-MS, 1 D and 2 D NMR, and ECD. Different from the well-known exo-type dimer, torreyanic acid, compounds 1 and 2 represent the first example of endo-type product derived from the intermolecular Diels-Alder reaction of two molecules of ambuic acid derivative with the identical absolute stereochemistry.

Intrinsic Nature of the Ultrafast Deexcitation Pathway of Mycosporine-like Amino Acid Porphyra-334.

Porphyra-334 is a member of natural UV-screening compounds named mycosporine-like amino acids found in several marine organisms. The UV excited porphyra-334 has been identified to deexcite quickly by puckering the intramolecular cyclohexenimine ring; however, the reason for such a ring-puckering occurrence is yet unclear. In this study, we show the ring-puckering to be the relaxation pathway of the UV excited π electron which shifts from the in-ring bond to the out-of-ring bond. The ring-puckering is characterized by the torsion among the in-ring and out-of-ring bonds. Since the π electron shift is possible in two different directions at the Franck-Condon UV excited state, it enables two ring-puckering pathways: the previously reported pathway and another one newly identified at present. We also examine the ring-unpuckering pathways which are an analogy of cis/trans photoisomerization, and we find them to be not suited for the π electron shift character of the UV excited state and thus not related to the deexcitation pathway. The present study provides insight into how porphyra-334 exerts the UV-screening ability based on its cyclohexenimine ring structure.

Characterization of Antioxidant Activity of Heated Mycosporine-like Amino Acids from Red Alga Dulse Palmaria palmata in Japan.

We recently demonstrated the monthly variation and antioxidant activity of mycosporine-like amino acids (MAAs) from red alga dulse in Japan. The antioxidant activity of MAAs in acidic conditions was low compared to that in neutral and alkali conditions, but we found strong antioxidant activity from the heated crude MAA fraction in acidic conditions. In this study, we identified and characterized the key compounds involved in the antioxidant activity of this fraction. We first isolated two MAAs, palythine, and porphyra-334, from the fraction and evaluated the activities of the two MAAs when heated. MAAs possess absorption maxima at around 330 nm, while the heated MAAs lost this absorption. The heated MAAs showed a high ABTS radical scavenging activity at pH 5.8-8.0. We then determined the structure of heated palythine via ESI-MS and NMR analyses and speculated about the putative antioxidant mechanism. Finally, a suitable production condition of the heated compounds was determined at 120 °C for 30 min at pH 8.0. We revealed compounds from red algae with antioxidant activities at a wide range of pH values, and this information will be useful for the functional processing of food.