Pretreatment for potable reuse: Enhancing the biological removal of 1,4-dioxane from landfill leachate through cometabolism with tetrahydrofuran.

1,4-Dioxane is a probable human carcinogen and a persistent aquatic contaminant. Cometabolic biodegradation of 1,4-dioxane is a promising low-cost and effective treatment technology; however, further demonstration is needed for treating landfill leachate. This technology was tested in two full-scale moving bed biofilm reactors (MBBRs) treating raw landfill leachate with tetrahydrofuran selected as the cometabolite. The raw leachate contained on average 82 µg/L of 1,4-dioxane and before testing the MBBRs removed an average of 38% and 42% of 1,4-dioxane, respectively. First, tetrahydrofuran was added to MBBR 1, and 1,4-dioxane removal was improved to an average of 73%, with the control MBBR removing an average of 37% of 1,4-dioxane. During this period, an optimal dose of 2 mg/L of tetrahydrofuran was identified. Tetrahydrofuran was then fed to both MBBRs, where the 1,4-dioxane removal was on average 73% and 80%. Cometabolic treatment at the landfill significantly reduced the concentration of 1,4-dioxane received from the landfill at a downstream wastewater treatment and indirect potable reuse facility, reducing the load of 1,4-dioxane from 44% to 24% after the study. PRACTITIONER POINTS: Cometabolic degradation of leachate 1,4-dioxane with THF in MBBRs is a feasible treatment technology and a low-cost technique when retrofitting existing biological treatment facilities. The MBBRs can be operated at a range of temperatures, require no operational changes beyond THF addition, and operate best at a mass ratio of THF to 1,4-dioxane of 24. Source control of 1,4-dioxane significantly reduces the concentration of 1,4-dioxane in downstream wastewater treatment plants and potable reuse facilities.

Synthesis and Characterization of Guanidinylated CO-Releasing Micelles Based on Biodegradable Polycarbonate.

As one of the gaseous signals in living cells, carbon monoxide (CO) not only participates in many biological activities but also serves as a therapeutic agent for the treatment of diseases. However, the limited applicability of CO in gas therapy emerges from the inconvenience of direct administration of CO. Here we reported the construction of guanidinylated CO-releasing micelles, which are composed of poly(trimethylene carbonate) (PTMC)-based CO donors. The in vitro studies demonstrated that micelles in the presence of light irradiation can induce cancer death, whereas no obvious toxicity to normal cells was observed. Moreover, the functionalization of guanidine groups imparts improved cellular uptake efficiency to micelles owing to the specific interactions with the surface of cells, which synergistically increase the anticancer capacity of the system. The guanidine-functionalized CO-releasing micelles provide a new strategy for the construction of CO-releasing nanocarriers, which are expected to find applications in gas therapeutics.

CO2-Based Polycarbonates through Ring-Opening Polymerization of Cyclic Carbonates Promoted by a NHC-Based Zinc Complex.

A backbone-substituted N-heterocyclic carbene (NHC) zinc complex, in combination with alcohol initiators, has been shown to be an effective catalyst for the ring-opening polymerization (ROP) of trimethylene carbonate (TMC) to poly(trimethylene carbonate) (PTMC) devoid of oxetane linkages. The ROP of TMC proceeded in solution to give PTMC, possessing controlled molecular mass (2500 < Mn < 10000) and low dispersity (D ∼ 1.2). Changing the alcohol initiators, PTMCs with different end-groups were obtained, included a telechelic polymer. The results of MALDI-ToF and NMR analysis confirmed the controlled/living nature of the present ROP catalytic system, where side reactions, such as inter- and intramolecular transesterifications, were minimized during the polymerization. Solution studies in different solvents demonstrated the polymerization reaction to proceed via a mechanism first order in monomer and in catalyst. The zinc complex was also able to convert substituted cyclic carbonates, which were purposely synthesized from renewable feedstocks such as CO2 and 1,3-diols. For the asymmetric 2-Me TMC monomer, good regioselectivity was observed (Xreg up to 0.92). The excellent control of the polymerization process was finally brought to light through the preparation of polycarbonate/polyether triblock copolymers by using polyethylene glycol (PEG) as a macroinitiator and of well-defined di- and triblock polycarbonate/polylactide copolymers by sequential ROP of TMC and L-LA.

Engineering Biodegradable Polyurethanes with Precisely Controlled Hierarchical Structures to Access Shape Memory Effect and Enhanced Bioactivities.

Biodegradable polymers with shape memory effects (SMEs) offer promising solutions for short-term medical interventions, facilitating minimally invasive procedures and subsequent degradation without requiring secondary surgeries. However, achieving a good balance among desirable SMEs, mechanical performance, degradation rate, and bioactivities remains a significant challenge. To address this issue, we established a strategy to develop a versatile biodegradable polyurethane (PPDO-PLC) with tunable hierarchical structures via precise chain segment control. Initial copolymerization of l-lactide and ε-caprolactone sets a tunable Tg close to body temperature, followed by block copolymerization with poly(p-dioxanone) to form a hard domain. This yields a uniform microphase-separation morphology, ensuring robust SME and facilitating the development of roughly porous surface structures in alkaline environments. Cell experiments indicate that these rough surfaces significantly enhance cellular activities, such as adhesion, proliferation, and osteogenic differentiation. Our approach provides a methodology for balancing biodegradability, SMEs, three-dimensional (3D) printability, and bioactivity in materials through hierarchical structure regulation.

Convenient Preparation, Thermal Properties and X-ray Structure Determination of 2,3-Dihydro-5,6,7,8-tetranitro-1,4-benzodioxine (TNBD): A Promising High-Energy-Density Material.

2,3-dihydro-5,6,7,8-tetranitro-1,4-benzodioxine (TNBD), molecular formula = C8H4N4O10, is a completely nitrated aromatic ring 1,4-benzodioxane derivative. The convenient method of TNBD synthesis was developed (yield = 81%). The detailed structure of this compound was investigated by X-ray crystallography. The results of the thermal analysis (TG) obtained with twice re-crystallized material revealed the onset at 240 °C (partial sublimation started) and melting at 286 °C. The investigated material degraded completely at 290-329 °C. The experimental density of 1.85 g/cm3 of TNBD was determined by X-ray crystallography. The spectral properties of TNBD (NMR, FT-IR and Raman) were explored. The detonation properties of TNBD calculated by the EXPLO 5 code were slightly superior in comparison to standard high-energy material-tetryl (detonation velocity of TNBD-7727 m/s; detonation pressure-278 kbar; and tetryl-7570 m/s and 226.4 kbar at 1.614 g/cm3, or 260 kbar at higher density at 1.71 g/cm3. The obtained preliminary results might suggest TNBD can be a potential thermostable high-energy and -density material (HEDM).

Biomimicking covalent organic frameworks nanocomposite coating for integrated enhanced anticorrosion and antifouling properties of a biodegradable magnesium stent.

The utilization of biodegradable magnesium (Mg) alloys in the fabrication of temporary non-vascular stents is an innovative trend in biomedical engineering. However, the heterogeneous degradation profiles of these biomaterials, together with potential bacterial colonization that could precipitate infectious or stenotic complications, are critical obstacles precluding their widespread clinical application. In pursuit of overcoming these limitations, this study applies the principles of biomimicry, particularly the hydrophobic and anti-fouling characteristics of lotus leaves, to pioneer the creation of nanocomposite coatings. These coatings integrate poly-trimethylene carbonate (PTMC) with covalent organic frameworks (COFs), to modify the stent's surface property. The strategic design of the coating's topography, porosity, and self-polishing capabilities collectively aims to decelerate degradation processes and minimize biological adhesion. The protective qualities of the coatings were substantiated through rigorous testing in both in vitro dynamic bile tests and in vivo New Zealand rabbit choledochal models. Empirical findings from these trials confirmed that the implementation of COF-based nanocomposite coatings robustly fortifies Mg implantations, conferring heightened resistance to both biocorrosion and biofouling as well as improved biocompatibility within bodily environments. The outcomes of this research elucidate a comprehensive framework for the multifaceted strategies against stent corrosion and fouling, thereby charting a visionary pathway toward the systematic conception of a new class of reliable COF-derived surface modifications poised to amplify the efficacy of Mg-based stents. STATEMENT OF SIGNIFICANCE: Biodegradable magnesium (Mg) alloys are widely utilized in temporary stents, though their rapid degradation and susceptibility to bacterial infection pose significant challenges. Our research has developed a nanocomposite coating inspired by the lotus, integrating poly-trimethylene carbonate with covalent organic frameworks (COF). The coating achieved self-polishing property and optimal surface energy on the Mg substrate, which decelerates stent degradation and reduces biofilm formation. Comprehensive evaluations utilizing dynamic bile simulations and implantation in New Zealand rabbit choledochal models reveal that the coating improves the durability and longevity of the stent. The implications of these findings suggest the potential COF-based Mg alloy stent surface treatments and a leap forward in advancing stent performance and endurance in clinical applications.

Meniscal repair with additive manufacture of bioresorbable polymer: From physicochemical characterization to implantation of 3D printed poly (L-co-D, L lactide-co-trimethylene carbonate) with autologous stem cells in rabbits.

Three-dimensional (3D) structures are actually the state-of-the-art technique to create porous scaffolds for tissue engineering. Since regeneration in cartilage tissue is limited due to intrinsic cellular properties this study aims to develop and characterize three-dimensional porous scaffolds of poly (L-co-D, L lactide-co-trimethylene carbonate), PLDLA-TMC, obtained by 3D fiber deposition technique. The PLDLA-TMC terpolymer scaffolds (70:30), were obtained and characterized by scanning electron microscopy, gel permeation chromatography, differential scanning calorimetry, thermal gravimetric analysis, compression mechanical testing and study on in vitro degradation, which showed its amorphous characteristics, cylindrical geometry, and interconnected pores. The in vitro degradation study showed significant loss of mechanical properties compatible with a decrease in molar mass, accompanied by changes in morphology. The histocompatibility association of mesenchymal stem cells from rabbit's bone marrow, and PLDLA-TMC scaffolds, were evaluated in the meniscus regeneration, proving the potential of cell culture at in vivo tissue regeneration. Nine New Zealand rabbits underwent total medial meniscectomy, yielding three treatments: implantation of the seeded PLDLA-TMC scaffold, implantation of the unseeded PLDLA-TMC and negative control (defect without any implant). After 24 weeks, the results revealed the presence of fibrocartilage in the animals treated with polymer. However, the regeneration obtained with the seeded PLDLA-TMC scaffolds with mesenchymal stem cells had become intimal to mature fibrocartilaginous tissue of normal meniscus both macroscopically and histologically. This study demonstrated the effectiveness of the PLDLA-TMC scaffold in meniscus regeneration and the potential of mesenchymal stem cells in tissue engineering, without the use of growth factors. It is concluded that bioresorbable polymers represent a promising alternative for tissue regeneration.

Effect of 1,4-Dioxane Solvent on ß-Glucuronidation Using Methyl 1,2,3,4-Tetra-O-acetyl-ß-D-glucuronate as the Glycosyl Donor.

A facile and selective ß-D-glucuronidation of alcohols, such as (-)-menthol, cholestanol, (+)- and (-)-borneols, and 2-adamantanol, using commercially available methyl 1,2,3,4-tetra-O-acetyl-ß-D-glucuronate as the glycosyl donor and trimethylsilyl bis(trifluoromethanesulfonyl)imide (Tf2NTMS) (0.5 equivalent) as the activator in 1,4-dioxane at 60 °C gave products in moderate yields. The addition of MS4A increased the ß : α ratios of D-glucuronides when cholestanol, (+)-borneol, and 2-adamantanol were used as the acceptor substrate.

Meldrum's Acid Furfural Conjugate MAFC: A New Entry as Chromogenic Sensor for Specific Amine Identification.

Bioactive amines are highly relevant for clinical and industrial application to ensure the metabolic status of a biological process. Apart from this, generally, amine identification is a key step in various bioorganic processes ranging from protein chemistry to biomaterial fabrication. However, many amines have a negative impact on the environment and the excess intake of amines can have tremendous adverse health effects. Thus, easy, fast, sensitive, and reliable sensing methods for amine identification are strongly searched for. In the past few years, Meldrum's acid furfural conjugate (MAFC) has been extensively explored as a starting material for the synthesis of photoswitchable donor-acceptor Stenhouse adducts (DASA). DASA formation hereby results from the rapid reaction of MAFC with primary and secondary amines, which has so far been demonstrated through numerous publications for different applications. The linear form of the MAFC-based DASA exhibits intense pink coloration due to its linear conjugated triene-2-ol conformation, which has inspired researchers to use this easy synthesizable molecule as an optical sensor for primary, secondary, and biogenic amines. Due to its new entry into amine identification, a collection of the literature exclusively on MAFC is demanded. In this mini review, we intend to present the state-of-the-art of MAFC as an optical molecular sensor in hopes to motivate researchers to find even more applications of MAFC-based sensors and methods that pave the way to their usage in medicinal applications.

Arylidene Meldrum's Acid: A Versatile Structural Motif for the Design of Enzyme-Responsive "Covalent-Assembly" Fluorescent Probes with Tailor-Made Properties.

Latent cyclic carbon-centered nucleophiles (latent C-nucleophiles) are recently proving their value in the field of reaction-based fluorescent probes, far beyond their primary utility in organic synthesis. They are typically used to introduce a Michael acceptor moiety acting as a recognition/reaction site for analyte to be detected or as a kinetic promoter of fluorogenic cascade reactions triggered by a reactive species. C-nucleophiles bearing a further reactive handle offer an additional opportunity for tuning the physicochemical/targeting properties or providing drug-releasing capabilities to these probes, through the covalent attachment of ad hoc chemical moiety. In order to implement such strategy to fluorogenic/chromogenic enzyme substrates based on the "covalent-assembly" principle, we have explored the potential of some functionalized derivatives of barbituric acid, piperidine-2,4-dione and Meldrum's acid. Our investigations based on the rational design and analytical validations of enzyme-responsive caged precursors of fluorescent pyronin dyes and 7-(diethylamino)coumarin-3-carboxylic acid, led to identify a versatile candidate suitable for this late-stage structural optimization approach. This Meldrum's acid derivative enables to either enhance water solubility or achieve the reversible conjugation of a targeting ligand, while promoting in situ formation of fluorophore upon enzymatic activation. This study opens the way to novel multifunctional fluorescence imaging probes and optically modulated small conjugate-based theranostics.

Effects of Chemical Composition on the Shape Memory Property of Poly(dl-lactide-co-trimethylene carbonate) as Self-Morphing Small-Diameter Vascular Scaffolds.

Smart materials have great potential in many biomedical applications, in which biodegradable shape memory polymers (SMPs) can be used as surgical sutures, implants, and stents. Poly(dl-lactide-co-trimethylene carbonate) (PDLLTC) represents one of the promising SMPs and is widely used in biomedical applications. However, the relationship between its shape memory property and chemical structure has not been fully studied and needs further elaboration. In this work, PDLLTC copolymers in different compositions have been synthesized, and their shape memory properties have been investigated. It has been found that the shape memory property is related to the chemical composition and polymeric chain segments. The copolymer with a DLLA/TMC ratio of 75:25 (PDLLTC7525) has been demonstrated with great shape fixation and recovery ratio at human body temperature. Furthermore, PDLLTC7525-based self-morphing small-diameter vascular scaffolds adhered with inner electrospun aligned gelatin/hyaluronic acid (Gel/HA) nanofibers have been constructed, as a merit of its shape memory property. The scaffolds have been demonstrated to facilitate the proliferation and adhesion of endothelial cells on the inner layer. Therefore, PDLLTC with tailorable shape memory properties represents a promising candidate for the development of SMPs, as well as for small-diameter vascular scaffolds construction.

The Reactions of N,N'-Diphenyldithiomalondiamide with Arylmethylidene Meldrum's Acids.

The Michael addition reaction between dithiomalondianilide (N,N'-diphenyldithiomalondiamide) and arylmethylidene Meldrum's acids, accompanied by subsequent heterocyclization, was investigated along with factors affecting the mixture composition of the obtained products. The plausible mechanism includes the formation of stable Michael adducts which, under the studied conditions, undergo further transformations to yield corresponding N-methylmorpholinium 4-aryl-6-oxo-3-(N-phenylthio-carbamoyl)-1,4,5,6-tetrahydropyridin-2-thiolates and their oxidation derivatives, 4,5-dihydro-3H-[1,2]dithiolo[3,4-b]pyridin-6(7H)-ones. The structure of one such product, N-methylmorpholinium 2,2-dimethyl-5-(1-(2-nitrophenyl)-3-(phenylamino)-2-(N-phenylthiocarbamoyl)-3-thioxopropyl)-4-oxo-4H-1,3-dioxin-6-olate, was confirmed via X-ray crystallography.

Effective Ligand Design: Zinc Complexes with Guanidine Hydroquinoline Ligands for Fast Lactide Polymerization and Chemical Recycling.

In this study, the synthesis of two new guanidine hydroquinoline ligands served as basis for six new zinc guanidine complexes. Two of these complexes showed very high activity in the lactide polymerization under industrial conditions. The lactide polymerization was demonstrated in solution and melt conditions observing high activity and molar masses up to 90 000 g mol-1 . Density functional theory studies elucidated the high activity of the complexes associated with the influence of the ligand backbone and the use of triflate counterions. On the way towards a circular economy, polymerization and depolymerization go hand in hand. So far, guanidine complexes have only shown their good activity in the ring opening polymerization of esters, and guanidine complexes with pure N donors have not been tested in recycling processes. Herein, the excellent ability of zinc guanidine complexes to catalyze both polymerization and depolymerization was demonstrated. The two most promising zinc complexes efficiently mediated the methanolysis of polylactide into methyl lactate under mild reaction conditions.

Sucralose as an oxidative-attenuation tracer for characterizing the application of in situ chemical oxidation for the treatment of 1,4-dioxane.

In situ chemical oxidation (ISCO) has become a widely used soil and groundwater remediation method. Oxidative-attenuation tracers can be used to provide real-time, explicit delineation of contaminant mass-transfer and transformation behavior during an ISCO remediation project. The objective of this study was to evaluate the potential of employing sucralose, a widely used artificial sweetener, as an oxidative-attenuation tracer to characterize the remediation efficiency of 1,4-dioxane (dioxane) by persulfate-based ISCO. Batch and miscible-displacement experiments were conducted to examine the degradation rate and transport behavior of sucralose compared to that of dioxane. Comparable magnitudes and rates of degradation were observed for sucralose and dioxane in batch-reactor experiments with soil and persulfate. The breakthrough curves of sucralose and dioxane transport in a soil-packed column were coincident. The retardation factors were 1.1 for both compounds, indicating limited sorption for both sucralose and dioxane by the soil. Limited degradation was observed in the miscible-displacement experiments, consistent with the short residence time compared to the half-lives of sucralose and dioxane. Persulfate transport and decomposition behavior in the soil-packed columns was similar in the presence of sucralose or dioxane. A simulated tracer test was conducted to illustrate the application of sucralose as an oxidative-attenuation tracer at the pilot scale. These results demonstrate the potential of sucralose as an oxidative-attenuation tracer to support the robust design of ISCO applications for dioxane. The oxidative-attenuation tracer test method is anticipated to be an effective approach for characterizing mass-removal behavior of other emerging contaminants with appropriate selection of tracer.

"Like Recycles Like": Selective Ring-Closing Depolymerization of Poly(L-Lactic Acid) to L-Lactide.

Chemical recycling of poly(L-lactic acid) to the cyclic monomer L-lactide is hampered by low selectivity and by epimerization and elimination reactions, impeding its use on a large scale. The high number of side reactions originates from the high ceiling temperature (Tc ) of L-lactide, which necessitates high temperatures or multistep reactions to achieve recycling to L-lactide. To circumvent this issue, we utilized the impact of solvent interactions on the monomer-polymer equilibrium to decrease the Tc of L-lactide. Analyzing the observed Tc in different solvents in relation to their Hildebrand solubility parameter revealed a "like recycles like" relationship. The decreased Tc , obtained by selecting solvents that interact strongly with the monomer (dimethyl formamide or the green solvent γ-valerolactone), allowed chemical recycling of high-molecular-weight poly(L-lactic acid) directly to L-lactide, within 1-4 h at 140 °C, with >95 % conversion and 98-99 % selectivity. Recycled L-lactide was isolated and repolymerized with high control over molecular weight and dispersity, closing the polymer loop.

Electrochemically Controlled Switchable Copolymerization of Lactide, Carbon Dioxide, and Epoxides.

Electrochemical redox-control is an emerging strategy for the regulation of polymerization process without the addition of external oxidants and reductants, which enables the control over composition, microstructure and properties of the polymer products. In this paper, based on the chemical selectivity of heterometallic Salen-Co-Mn complexes of different valences, an electrochemically switchable strategy was developed for the copolymerization of lactide (LA), CO2 and epoxides. The switchable redox reactions endowed this system with the capability to easily synthesize a multi-block copolymer of polylactide (PLA) and polycarbonate (PC). Moreover, the multi-block copolymer could be further modified by introducing various monomers with different microstructures and functional groups.

A Comprehensive Investigation of the Structural, Thermal, and Biological Properties of Fully Randomized Biomedical Polyesters Synthesized with a Nontoxic Bismuth(III) Catalyst.

Aliphatic polyesters are the most common type of biodegradable synthetic polymer used in many pharmaceutical applications nowadays. This report describes the ring-opening polymerization (ROP) of l-lactide (L-LA), ε-caprolactone (CL) and glycolide (Gly) in the presence of a simple, inexpensive and convenient PEG200-BiOct3 catalytic system. The chemical structures of the obtained copolymers were characterized by 1H- or 13C-NMR. GPC was used to estimate the average molecular weight of the resulting polyesters, whereas TGA and DSC were employed to determine the thermal properties of polymeric products. The effects of temperature, reaction time, and catalyst content on the polymerization process were investigated. Importantly, the obtained polyesters were not cyto- or genotoxic, which is significant in terms of the potential for medical applications (e.g., for drug delivery systems). As a result of transesterification, the copolymers obtained had a random distribution of comonomer units along the polymer chain. The thermal analysis indicated an amorphous nature of poly(l-lactide-co-ε-caprolactone) (PLACL) and a low degree of crystallinity of poly(ε-caprolactone-co-glycolide) (PCLGA, Xc = 15.1%), in accordance with the microstructures with random distributions and short sequences of comonomer units (l = 1.02-2.82). Significant differences in reactivity were observed among comonomers, confirming preferential ring opening of L-LA during the copolymerization process.

Amine-substituent induced highly selective and rapid "turn-on" detection of carcinogenic 1,4-dioxane from purely aqueous and vapour phase with novel post-synthetically modified d10-MOFs.

Herein, an amine decorated Cd(II) metal-organic framework (MOF) with a uninodal 6-c topology was synthesized as a suitable platform for facile post-synthetic modification (PSM). The as-synthesized parent d10-MOF (1) with free -NH2 centers, when functionalized with two different carbonyl substituents (1-naphthaldehyde and benzophenone) of varying conjugation, produces two novel luminescent MOFs (LMOFs) viz.PSM-1 and PSM-2. The judicious incorporation of carbonyl substituents into the skeleton of 1 was rationalized via ESI-MS, 1H-NMR, FT-IR and PXRD analyses. Interestingly, both PSM-1 and PSM-2 show 'turn-on' luminescent behaviour in the presence of 1,4-dioxane with the limit of detection (LOD) as 1.079 ppm and 2.487 ppm, respectively, with prompt response time (∼55 s & ∼58 s, respectively). The inhibition of PET is comprehended to be the prime reason for luminescence enhancement upon interaction with the targeted analyte which was further validated from DFT calculations. In continuation, the PSM-MOFs were equally responsive towards 1,4-dioxane in several complex environmental matrices and cosmetic products. Additionally, vapor phase detection of 1,4-dioxane using PSM-MOFs has also been demonstrated as an additional advantage ensuring propagation of future research endeavour.

Construction and activity evaluation of novel benzodioxane derivatives as dual-target antifungal inhibitors.

Ergosterol exert the important function in maintaining the fluidity and osmotic pressure of fungal cells, and its key biosynthesis enzymes (Squalene epoxidase, SE; 14 α-demethylase, CYP51) displayed the obvious synergistic effects. Therefore, we expected to discover the novel antifungal compounds with dual-target (SE/CYP51) inhibitory activity. In the progress, we screened the different kinds of potent fragments based on the dual-target (CYP51, SE) features, and the method of fragment-based drug discovery (FBDD) was used to guide the construction of three different series of benzodioxane compounds. Subsequently, their chemical structures were synthesized and evaluated. These compounds displayed the obvious biological activity against the pathogenic fungal strains. Notably, target compounds 10a-2 and 22a-2 possessed the excellent broad-spectrum anti-fungal activity (MIC50, 0.125-2.0 µg/mL) and the activity against drug-resistant strains (MIC50, 0.5-2.0 µg/mL). Preliminary mechanism studies have confirmed that these compounds effectively inhibited the dual-target (SE/CYP51) activity, they could cause fungal rupture and death by blocking the bio-synthetic pathway of ergosterol. Further experiments discovered that compounds 10a-2 and 22a-2 also maintained a certain of anti-fungal effect in vivo. In summary, this study not only provided the new dual-target drug design strategy and method, but also discover the potential antifungal compounds.

Reverse orientation in the ultrasound-assisted [3 + 2]-cycloaddition reaction of nitrile imines with 3-formylchromone-Meldrum's acid adducts.

The [3 + 2]-cycloaddition reaction of nitrile imines with 2,2-dimethyl-5-[(4-oxo-4H-chromen-3-yl)methylene]-1,3-dioxane-4,6-dione tends to form the reverse-orientation products under ultrasound irradiation in EtOH in the presence of Et3N. Evidence for the structure of product 5b was obtained from single-crystal X-ray analysis.