Discovery of novel amide derivatives as potent quorum sensing inhibitors of Pseudomonas aeruginosa.

With the increasing reports of antibiotic resistance in this species, Pseudomonas aeruginosa is a common human pathogen with important implications for public health. Bacterial quorum sensing (QS) systems are potentially broad and versatile targets for developing new antimicrobial compounds. While previous reports have demonstrated that certain amide compounds can inhibit bacterial growth, there are few reports on the specific inhibitory effects of these compounds on bacterial quorum sensing systems. In this study, thirty-one amide derivatives were synthesized. The results of the biological activity assessment indicated that A9 and B6 could significantly inhibit the expression of lasB, rhlA, and pqsA, effectively reducing several virulence factors regulated by the QS systems of PAO1. Additionally, compound A9 attenuated the pathogenicity of PAO1 to Galleria mellonella larvae. Meanwhile, RT-qPCR, SPR, and molecular docking studies were conducted to explore the mechanism of these compounds, which suggests that compound A9 inhibited the QS systems by binding with LasR and PqsR, especially PqsR. In conclusion, amide derivatives A9 and B6 exhibit promising potential for further development as novel QS inhibitors in P. aeruginosa.

Discovery and structural optimization of 3-O-ß-Chacotriosyl betulonic acid saponins as potent fusion inhibitors of Omicron virus infections.

The recent global Omicron epidemics underscore the great need for the development of small molecule therapeutics with appropriate mechanisms. The trimeric spike protein (S) of SARS-CoV-2 plays a pivotal role in mediating viral entry into host cells. We continued our efforts to develop small-molecule SARS-CoV-2 entry inhibitors. In this work, two sets of BA derivatives were designed and synthesized based on the hit BA-1 that was identified as a novel SARS-CoV-2 entry inhibitor. Compound BA-4, the most potent one, showed broad inhibitory activities against pOmicron and other pseudotyped variants with EC50 values ranging 2.73 to 5.19 µM. Moreover, pSARS-CoV-2 assay, SPR analysis, Co-IP assay and the cell-cell fusion assay coupled with docking and mutagenesis studies revealed that BA-4 could stabilize S in the pre-fusion step to interfere with the membrane fusion, thereby displaying promising inhibition against Omicron entry.

Catalytic asymmetric addition of thiols to silyl glyoxylates for synthesis of multi-hetero-atom substituted carbon stereocenters.

A chiral Lewis acid-catalyzed enantioselective addition of thiols to silyl glyoxylates was developed. The reaction proceeds well with a broad range of thiols and acylsilanes, affording the target tertiary chiral α-silyl-α-sulfydryl alcohols with multi-hetero-atom carbon stereocenters in excellent yields (up to 99%) and enantioselectivities (up to 98% ee). A series of control experiments were conducted to elucidate the reaction mechanism.

Novel Quaternary Ammonium-Functionalized Covalent Organic Frameworks/Poly(2,6-dimethyl-1,4-phenylene oxide) Hybrid Anion Exchange Membranes with Enhanced Ion Conductivity and Stability.

Here we report a new hybrid anion exchange membrane with enhanced hydroxide conductivity and excellent chemical and dimensional stability by incorporating quaternary ammonium (QA)-functionalized covalent organic framework into brominated poly(2,6-dimethyl-1,4-phenylene oxide) (BPPO). N,N,N',N' -Tetramethyl-1,6-hexanediamine (TMHDA) was impregnated into the pores of COF-LZU1 via a vacuum-assisted method, followed by reacting with allyl bromide. The generated QA groups were immobilized within the highly ordered pores of COF-LZU1 via in situ polymerization, forming long-range ordered multiple ion channels. The obtained QA@COF-LZU1 was then mixed with QAPPO to construct a hybrid anion exchange membrane for anion exchange membrane fuel cells (AEMFCs). The hydroxide conductivity of QA@COF-LZU1/PPO hybrid membrane increased up to 168.00 mS cm-1 at 80 °C, about 77% higher than that of pristine membrane. In addition, alkaline stability and thermal stability of the hybrid membranes were obviously enhanced. The excellent performance and the outstanding chemical stability render the COF hybrid membrane a good candidate for the application in AEMFCs.

Divergent Synthesis of Enantioenriched ß-Functional Amines via Desymmetrization of meso-Aziridines with Isocyanides.

A highly enantioselective ring-opening desymmetrization of meso-aziridines with isocyanides was achieved in the presence of a chiral N,N'-dioxide/Mg(OTf)2 complex. The in situ generated chiral 1,4-zwitterionic intermediates were successfully trapped by intramolecular oxygen- and carbon-based nucleophiles or exogenous H2O and TMSN3, enabling a collective synthesis of various chiral vicinal amino-oxazoles, spiroindolines, ß-amino amides, and tetrazole derivative in moderate to high yields with excellent enantioselectivities.

A Conjugated Polymer Fluorescent Sensor for Continuous Identification of Copper(II) and Pyrophosphate in Blood Serum and Synovial Fluid.

A novel "on-off-on" super-sensitive conjugated polymer fluorescence sensor (PPE-DPA) was developed and it was applied to realize the continuous recognition of Cu2+ and pyrophosphate (PPi). The fluorescence intensity decreased linearly with the change of Cu2+ from 0.05 to 5.0 µmol L-1 and the limit of detection was 24 nmol L-1. The fluorescence intensity was linearly enhanced with the increase of PPi from 0.5 to 12.0 µmol L-1 and the limit of detection was 230 nmol L-1. In addition, this method was applied to detect PPi in the blood serum and synovial fluid of patients with arthritis and satisfactory results were obtained. Thus, the PPE-DPA is not only an effective tool for detecting Cu2+ and PPi in samples, but also presents a potential way to diagnose arthritis.

Fluorescence chemical sensor for determining trace levels of nitroaromatic explosives in water based on conjugated polymer with guanidinium side groups.

A novel fluorescent conjugated polymer (poly(2-amino-N-(2-((4-ethynylphenyl) ethynyl) phenyl)-5-guanidinopentanamide)-1,4-phenylethynylene-1,4-phenyleneethynylene, PPE-Arg) was synthesized in this paper. We found that PPE-Arg could be quenched by picric acid (PA). Photoinduced electron transfer (PET) mechanism can be used to describe the fluorescence quenching of PPE-Arg. It could be speculated that the photo-induced electrons may be transferred from PPE-Arg to nitroaromatic explosives. In this paper, the experiment conditions and detection performance of PPE-Arg were systematically studied. The experiment results demonstrate PPE-Arg as a sensor for PA has a good linear range from 5 × 10-7 to 6 × 10-5 mol L-1 with the calculated limit of detection (LOD) to be 1.0 × 10-7 mol L-1. Meanwhile, reaction time between PPE-Arg and PA is less than 1 min. This proposed sensor was applied to rapidly detect nitroaromatic explosives in environmental water samples and satisfactory results were obtained.

Residue analysis of tetracyclines in milk by HPLC coupled with hollow fiber membranes-based dynamic liquid-liquid micro-extraction.

A novel hollow fiber membranes-based dynamic liquid-liquid micro-extraction (HF-DLLME) coupled with HPLC-UV detection has been developed for the residue analysis of tetracyclines in milk samples without deproteinization and degreasing. The influences of experimental parameters were investigated and optimized. The method showed a good performance. The limits of detection (LOD) are in the range of 0.95-3.6µg/L. The recoveries in spiked samples range from 92.38 to 107.3%. The relative standard deviations (RSDs) are lower than 8.66%. The advantages of this method are simple operation, high efficiency, absence of sample carryover and low cost.

Conjugated polymer with carboxylate groups-Hg2+ system as a turn-on fluorescence probe for label-free detection of cysteine-containing compounds.

In this work, a turn on fluorescent sensor, based on Hg2+ coordination conjugated polymer, was developed to detect cysteine-containing compounds. The fluorescence of conjugated polymer (poly(2,5-bis (sodium 4-oxybutyrate) -1,4 - phenylethynylene-alt-1,4-phenyleneethynylene; PPE-OBS) would be quenched by Hg2+ because of the coordination-induced aggregation and electron transfers of PPE-OBS toward Hg2+. When there were some cysteine-containing compounds in PPE-OBS-Hg2+ system, the fluorescence of PPE-OBS would be recovered. It indicated that the PPE-OBS-Hg2+ system could be used to detect cysteine-containing compounds. Under the optimized conditions, the experiment results showed that there were particularly linear range, high sensitivity and selectivity over other amino acids. The limit of detection (LOD) of cysteine (Cys), homocysteine (Hcy) and glutathione (GSH) were 0.725µmolL-1, 0.982µmolL-1 and 1.21µmolL-1 by using this sensor. In addition, Cys standard recovery in several green tea drink and honey samples was also demonstrated. The recovery of Cys was range from 96.3 to 105.0% and RSD was less than 3.25%. The satisfactory results demonstrated that the proposed method could be as a potential fluorescent method for determining cysteine-containing compounds in real samples.

Study of Fluorescent Imaging of Se (IV) in Living Cells Using a Turn-on Fluorescent Probe Based on a Rhodamine Spirolactame Derivative.

A highly selective fluorescent probe 2-(2-(2-aminoethylamino)ethyl)-3',6'-bis(ethylamino)-2',7'-dimethylspiro[isoindoline-1,9'-xanthen]-3-one (ABDO) for Se (IV) had been synthesized in our earlier report. In this study, this fluorescent sensor is applied on analysis fluorescent imaging of Se (IV) in Hela cells. The experiment conditions, such as the MTT assay, different concentration of saline, incubated time of Hela cells with ABDO and Se (IV), and intracellular action position of Se (IV), are investigated. Through a series of experiments, the fluorescent image of Se (IV) in Hela cells can be observed when the cells cultured by 2 µM ABDO and 2 µM Se (IV) for 210 min. And the intracellular action position of Se (IV) is verified after the co-localization experiments are done. It is mitochondria. These experimental results show that ABDO will be an eagerly anticipated sensor for fluorescent imaging analysis of selenium ion in living cells. Besides, we also can use the complexes of ABDO-Se to observe morphology and distribution of mitochondria in cells like JG-B.

Highly Sensitive Fluorescence Detection of Hg2+ Based on a Water-soluble Conjugated Polymer with Carboxylate Groups.

A label-free, highly selective, and highly sensitive fluorescent sensor to detect Hg2+ was developed using a water-soluble conjugated polymer with carboxylate groups (poly(2,5-bis(sodium 4-oxybutyrate)-1,4-phenylethynylene-alt-1,4-phenyleneethynylene, PPE-OBS) in this work. The fluorescence of PPE-OBS would be quenched because of the effect among the unique coordination-induced aggregation and electron transfers of PPE-OBS toward Hg2+. The linear relationship between the fluorescence intensity and concentration of Hg2+ was observed within the range from 6 × 10-8 to 8 × 10-5 mol L-1 (R2 = 0.9985), and the limit of detection was 2.10 × 10-9 mol L-1. The proposed method was applied to detect Hg2+ in environmental water samples, and satisfactory results were obtained.