Here, we present a straightforward α-trans-selective hydroboration of alkynyl sulfones with NHC-boranes without the need for a catalyst. This reaction is compatible with a wide range of substrates for efficiently producing structurally diverse α-borylated vinyl sulfones in satisfactory yields. The hydride transfer from NHC-borane 2a to alkynyl triflone 1b is studied by density functional theory (DFT) calculations for trans-hydroboration. Moreover, a regiodivergent deuterated semihydrogenation of alkynyl triflones has also been developed using D2O as the deuterium source. A variety of diversity-oriented D-containing vinyl triflones were prepared in good to excellent yields with excellent deuterium incorporation ratios. Synthetic manipulations of the deuterated products are achieved for the conversion into valuable deuterated molecules, indicating the utility of this protocol.
Rhodotorula spp. has been studied as one powerful source for a novel cell factory with fast growth and its high added-value biomolecules. However, its inadequate genome and genomic annotation have hindered its widespread use in cosmetics and food industries. Rhodotorula glutinis QYH-2023, was isolated from rice rhizosphere soil, and the highest quality of the genome of the strain was obtained at chromosome level (18 chromosomes) than ever before in red yeast in this study. Comparative genomics analysis revealed that there are more key gene copies of carotenoids biosynthesis in R. glutinis QYH-2023 than other species of Rhodotorula spp. Integrated transcriptome and metabolome analysis revealed that lipids and carotenoids biosynthesis was significantly enriched during fermentation. Subsequent investigation revealed that the over-expression of the strain three genes related to carotenoids biosynthesis in Komagataella phaffii significantly promoted the carotenoid production. Furthermore, in vitro tests initially confirmed that the longer the fermentation period, the synthesized metabolites controlled by R. glutinis QYH-2023 genome had the stronger anti-inflammatory properties. All of the findings revealed a high-quality reference genome which highlight the potential of R. glutinis strains to be employed as chassis cells for biosynthesizing carotenoids and other active chemicals.
Carotenoids , Genome, Fungal , Rhodotorula , Carotenoids/metabolism , Rhodotorula/genetics , Rhodotorula/metabolism , Anti-Inflammatory Agents/pharmacology , Fermentation , Chromosomes, Fungal/genetics , Genomics/methods , Transcriptome
A gold(I)-catalyzed hydroamination/cycloisomerization cascade reaction was developed to yield indolizino[8,7-b]indole and indolo[2,3-a]-quinolizine derivatives from 2-ethynyltryptamides. The optimal conditions were determined by condition screening, and the functional group tolerances of these reactions were explored based on synthetic substrates. An insight into the explanation on the selectivity of the ring closure was obtained by density functional theory calculations. A plausible mechanism for the cascade reactions was proposed. Derivatization of the indolizino[8,7-b]indole and total synthesis of nauclefidine demonstrated the practicality of this strategy.
Herein, we present a green scheme for the divergent synthesis of two polysubstituted quinolines from a singular substrate via exploiting free-radical duality. Photocatalytically generated imine radicals produce 3,4-disubstituted quinolines via a novel rearrangement in the presence of an inorganic base. Alternatively, they react in the presence of an organic base to furnish 2,3-disubstituted quinolines. Mechanism studies support the hypothesis that the electrophilic/nucleophilic bias of free radicals can be adjusted by altering the reaction conditions.
Antibiotics can cure diseases caused by bacterial infections, but their widespread use can have some side effects, such as probiotic reduction. There is an urgent need for such agents that can not only alleviate the damage caused by antibiotics, but also maintain the balance of the gut microbiota. In this study, we first characterized the nanocrystalline cellulose (NCC) extracted from plant jute (Corchorus olitorius L.) leaves. Next, we evaluated the protective effect of jute NCC and cellulose on human model gut bacteria (Lacticaseibacillus rhamnosus and Escherichia coli) under antibiotic stress by measuring bacterial growth and colony forming units. We found that NCC is more effective than cellulose in adsorbing antibiotics and defending the gut bacteria E. coli. Interestingly, the low-dose jute NCC clearly maintained the balance of key gut bacteria like Snodgrassella alvi and Lactobacillus Firm-4 in bees treated with tetracycline and reduced the toxicity caused by antibiotics. It also showed a more significant protective effect on human gut bacteria, especially L. rhamnosus, than cellulose. This study first demonstrated that low-dose NCC performed satisfactorily as a specific probiotic to mitigate the adverse effects of antibiotics on gut bacteria.
Fatigue failure, third-party destruction and internal corrosion may easily trigger gas and oil leakage during the operation of submarine multiphase pipelines. In order to analyze the underwater gas-oil plume development and migration law, a 3D model based on coupled Eulerian-Lagrangian numerical approach is proposed. The model is validated by laboratory experiment and the dynamic dispersion process of gas-oil plume in a large scale shallow sea environmental is further explored. Influencing factors such as leak location, leak size and water depth, flow pattern are investigated. The simulated results show that leak location affects the gas-oil plume migration behaviors by influencing the leakage amount. Water depth significantly affects gas-oil migration and the separation of gas plume and oil plume is gradually apparent as water depth increases. This study fills in the gap of ignoring the influence of flow pattern previously and is expected to help build more accurate emergency response guidelines.
Water Pollutants, Chemical , Water Pollutants, Chemical/analysis , Water , Ships
Spiro[indoline-3,3'-pyrrolidine] and spiro[indoline-3,3'-piperidine] derivatives were synthesized in a substitution-controlled manner under the catalysis of cationic gold(I) species in the presence of Hantzsch ester (HEH). The optimal reaction condition was determined by screening, and the functional group tolerances of these two pathways were examined by readily synthetic substrates. The endo and exo selectivities of these cyclizations were elucidated by density functional theory calculations, and a plausible mechanism for these transformations was proposed.
Density functional theory calculations were applied to predict the pathways of gold(I)-catalyzed cycloisomerization of the indole substrates with 1,6-enynes, which were consistent with the ensuing experimental results. The substitution-controlled synthesis led to the formation of 1H-pyrido[4,3-b]indole and spiro[indoline-3,3'-pyridine] derivatives in a tunable way. The reactions had good functional group tolerances, and a possible mechanism was proposed based on the computational and experimental results.
The regioselectivity for gold(I)-catalyzed intramolecular cycloisomerizations of tryptamine-ynamides has long been elusive despite various synthetic examples of similar substrates being available. Computational studies were carried out to provide insight into the mechanisms and the origin of the substrate-dependent regioselectivity of these transformations. Based on the analyses of non-covalent interactions, distortion/interaction, and energy decomposition on the interactions between the terminal substituent of alkynes and the gold(I) catalytic ligand, the electrostatic effect was determined to be the key factor for α-position selectivity while the dispersion effect was determined to be the key factor for ß-position selectivity. Our computational results were consistent with the experimental observations. This study provides useful guidance for understanding other similar gold(I)-catalyzed asymmetric alkyne cyclization reactions.
A visible-light-initiated trifluoromethylation/remote aliphatic C-H alkynylation of α-alkyl-substituted vinyl azides using acetylenic triflones as both the trifluoromethyl and alkyne donors is described. The reaction occurred under environmentally benign and radical initiator-free reaction conditions, affording γ-alkynylated trifluoromethyl ketone derivatives with a broad scope of substituents. Mechanistic studies suggested that the reaction is initiated via a triplet-triplet energy transfer between the 4CzIPN catalyst and acetylenic triflone, followed by fragmentation to generate a trifluoromethyl radical and an alkynyl radical.
Despite the large number of dicarboxylates' receptors, the dual channel ones capable of recognizing and removing of phthalate anion are rare and the task remains challenging. In this paper, a facilely synthesized amphiphilic macrocyclic acylhydrazone dimer (AMAD) can not only detect phthalate anion selectively, through both color changes and turn-on fluorescence in solution as well as in solid state, but is also able to remove it from either water or organic solvents. The current study paves the way for the search of more multiple functional receptors of dicarboxylates anions.
Despite the large number of synthetic macrocycles, the cubarenes, the quadrangular-shaped macrocyclic arenes, remain less investigated, possibly due either to synthetic challenges or to the lack of suitable building blocks. In this paper, a N-embedded cubarene (cub[4]indolocarbazole) is facilely synthesized by FeCl3·6H2O-catalyzed cyclization in dichloromethane. The endo cavity of cub[4]indolocarbazole can bury quaternary ammonium salts in an intramolecular manner, whereas the intermolecular interaction between its exo walls with Cu2+ generates two-dimensional supramolecular tessellation.
In this study, we designed and synthesized a new class of aggregation-induced emission luminogens, which was inspired and developed from the structure of tetraphenyl-1,3-butadienes derivative (TPB-1) through the minus strategy by removing one of the phenyl groups. Among them, L1 and L4 exhibited an aggregation-induced emission effect and multistimuli-responsive chromic behavior. Moreover, two types of single crystals of L1 were obtained, and their different emission behaviors were elucidated clearly by analyzing the single-crystal data.
Development of new mechanochromic luminescent (MCL) materials from aggregation-induced emission luminogens (AIEgens) has attracted wide attention due to their potential application in multiple areas. However, rational design and crafting of new MCL materials from the simple AIEgens skeleton is still a big challenge because of the undesirable concentration quenching effect. In this study, we have constructed a new class of MCL materials by adding one phenyl as a new rotator and incorporating one pair of electron donor (D) and acceptor (A) into the system of rofecoxib skeleton. This strategy endowed the compounds (Y1-Y8) with tunable emission behavior and some of them with the AIE effect and reversible MCL behavior. These properties may be caused by the highly twisted conformation and loosely molecular packing modes, which were elucidated clearly by analyzing the data of single-crystal X-ray diffraction, powder X-ray diffraction, and differential scanning calorimetry. Further investigation revealed that Y7 displayed acidochromic property due to the protonation of the nitrogen atom. Moreover, Y7, as a typical compound, showed its potential applications in the area of anticounterfeiting, pH sensor, and LD-specific bioimaging.
Fluorescent Dyes , Luminescence , Fluorescent Dyes/chemistry , Lactones , Sulfones
The development of aggregation-induced emission luminogens (AIEgens) has attracted increasing attention due to their potential applications in various areas in recent years. In this study, a facile conversion from aggregation-caused quenching (ACQ) to aggregation-induced emission (AIE) was achieved by an efficient regioisomerization strategy based on the rofecoxib scaffold. Two compounds, named PYR2 and PYR4, were identified as regioisomers of rofecoxib derivatives to show dramatically different fluorescent properties. Compound PYR2 with an ortho-substituted piperidine group showed typical AIE activity while compound PYR4 with a para-piperidine group exhibited typical ACQ behavior. Notably, compound PYR2 showed polymorphism with two forms of crystals. It was also endowed with reversible mechanochromic luminescence and acidochromic properties. The different fluorescent properties were elucidated by UV/Vis absorption spectroscopy, powder X-ray diffraction, differential scanning calorimetry, and thermogravimetric analyses. Its application as a security ink and in lipid droplets imaging have been demonstrated.
Fluorescent Dyes , Sulfones , Fluorescent Dyes/chemistry , Lactones , Luminescence
A Ag(I)/PPh3-catalyzed chelation-controlled cycloisomerization of tryptamine-ynamide was developed to access the spiro[indole-3,4'-piperidine] scaffold in a racemic and diastereoselective manner. The diastereoselective products were achieved by a chiron approach. Density functional theory (DFT) calculations indicated that strong non-covalent effects between the substrate and catalyst/ligand complex stabilized the spiroindoleninium intermediate via cation-π-π interactions.
Glioma, especially the most aggressive type glioblastoma multiforme, is a malignant cancer of the central nervous system with a poor prognosis. Traditional treatments are mainly surgery combined with radiotherapy and chemotherapy, which is still far from satisfactory. Therefore, it is of great clinical significance to find new therapeutic agents. Serving as an inhibitor of differentiation, protein ID2 (inhibitor of DNA binding 2) plays an important role in neurogenesis, neovascularization and malignant development of gliomas. It has been shown that ID2 affects the malignant progression of gliomas through different mechanisms. In this study, a pharmacophore-based virtual screening was carried out and 16 hit compounds were purchased for pharmacological evaluations on their ID2 inhibitory activities. Based on the cytotoxicity of these small-molecule compounds, two compounds were shown to effectively inhibit the viability of glioma cells in the micromolar range. Among them, AK-778-XXMU was chosen for further study due to its better solubility in water. A SPR (Surface Plasma Resonance) assay proved the high affinity between AK-778-XXMU and ID2 protein with the KD value as 129 nM. The plausible binding mode of ID2 was studied by molecular docking and it was found to match AGX51 very well in the same binding site. Subsequently, the cancer-suppressing potency of the compound was characterized both in vitro and in vivo. The data demonstrated that compound AK-778-XXMU is a potent ID2 antagonist which has the potential to be developed as a therapeutic agent against glioma.
Antineoplastic Agents/pharmacology , Brain Neoplasms/drug therapy , Drug Discovery , Glioma/drug therapy , Inhibitor of Differentiation Protein 2/antagonists & inhibitors , Small Molecule Libraries/pharmacology , Antineoplastic Agents/chemical synthesis , Antineoplastic Agents/chemistry , Brain Neoplasms/metabolism , Brain Neoplasms/pathology , Cell Proliferation/drug effects , Dose-Response Relationship, Drug , Drug Evaluation, Preclinical , Drug Screening Assays, Antitumor , Glioma/metabolism , Glioma/pathology , Humans , Inhibitor of Differentiation Protein 2/metabolism , Models, Molecular , Molecular Structure , Small Molecule Libraries/chemical synthesis , Small Molecule Libraries/chemistry , Structure-Activity Relationship , Tumor Cells, Cultured
Aggregation-induced emission (AIE) has attracted much attention in the past 2 decades. To develop novel AIE-active materials, ACQ-to-AIE transformation via regioisomerization is one of the most straightforward method. However, most of the reported ACQ-to-AIE transformations are achieved by migrating bulky units. In this work, a facile conversion was realized by migrating a small pyrrolidinyl group from para- to ortho-position on the rofecoxib scaffold. As a result, a pair of new isomers named MOX2 and MOX4 exhibited AIE behavior and ACQ activity, respectively. Moreover, MOX2 also showed solvatochromic, mechanochromic, and acidochromic properties with reversible multi-stimulus behavior. Single crystal X-ray analysis of MOX2 revealed that the molecular conformation and its packing mode were responsible for the AIE emission behavior. Further investigation indicated that MOX2 showed high lipid droplets staining selectivity. Taken together, the current work not only provides a new design philosophy for achieving ACQ-to-AIE conversion by migrating a small pyrrolidinyl group but also presents a promising candidate MOX2 for potential applications such as in security ink, optical recording and biological applications.
In this work, we synthesized a pair of positional isomers by attaching a small electron-donating pyrrolidinyl group at ortho- and para-positions of a conjugated core. These isomers exhibited totally different fluorescent properties. PDB2 exhibited obvious aggregation-induced emission properties. In contrast, PDB4 showed the traditional aggregation-caused quenching effect. Their different fluorescent properties were investigated by absorption spectroscopy, fluorescence spectroscopy, density functional theory calculations and single-crystal structural analysis. These results indicated that the substituent position of the pyrrolidinyl groups affects the twisted degree of the isomers, which further induces different molecular packing modes, thus resulting in different fluorescent properties of these two isomers. This molecular design concept provided a new accurate strategy for designing new aggregation-induced emission luminogens.
During early periods of salt stress, reduced stomatal opening can prevent water loss and wilting. Abscisic acid (ABA) signal plays an important role in this process. Here, we show that cucumber grafted onto pumpkin exhibits rapid stomatal closure, which helps plants to adapt to osmotic stress caused by salinity. Increased ABA contents in the roots, xylem sap, and leaves were evaluated in two grafting combinations (self-grafted cucumber and cucumber grafted onto pumpkin rootstock). The expression levels of ABA biosynthetic or signaling related genes NCED2 (9-cis-epoxycarotenoid dioxygenase gene 2), ABCG22 (ATP-binding cassette transporter genes 22), PP2C (type-2C protein phosphatases), and SnRK2.1 (sucrose non-fermenting 1-related protein kinases 2) were investigated. Results showed that a root-sourced ABA signal led to decreased stomatal opening and transpiration in the plants grafted onto pumpkin. Furthermore, plants grafted onto pumpkin had increased sensitivity to ABA, compared with self-grafted cucumbers. The inhibition of ABA biosynthesis with fluridon in roots increased the transpiration rate (Tr) and stomatal conductance (Gs) in the leaves. Our study demonstrated that the roots of pumpkin increases the sensitivity of the scion to ABA delivered from the roots to the shoots, and enhances osmotic tolerance under NaCl stress. Such a mechanism can be greatly exploited to benefit vegetable production particularly in semiarid saline regions.
