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Rapid and accurate analysis of zinc in seminal fluid is an important tool for male infertility diagnosis and forensic investigation of sexual assault. Among the traditional techniques employed for this purpose, colorimetric solid-state sensors offer a simple and efficient alternative for screening this analyte. Herein, we evaluated the feasibility of using solution blow spinning as a fast, simple, and cost-effective method to develop porous membranes that can be manufactured as low-cost colorimetric solid-state sensing materials. Specifically, we report a one-step approach to prepare blown spun polylactic acid (PLA)/poly(ethylene oxide) (PEO) fibrous membranes modified with 1-(2-pyridylazo)-2-naphthol (PAN) for the quantitative and qualitative screening of Zn 2+ in human seminal fluid. The fibrous membranes were fully characterized and then used to prepare discs and swabs. By digital image colorimetry, a spot-like assay was established using PLA/PEO@PAN membrane discs, which under optimized conditions, exhibited a linear range of up to 15 mg L -1 , a limit of detection of 0.06 mg L -1 and high selectivity in the presence of several interfering species commonly found in seminal fluid. Additionally, the sensor was successfully applied in the detection of Zn 2+ in human semen samples, showing no significant differences compared to the standard method. Furthermore, PLA/PEO@PAN swabs were employed in a naked-eye presumptive test to identify semen stains, showing satisfactory visual response even in the presence of only 0.11 μg of zinc. Moreover, the swabs' color changes were highly unambiguous, revealing a concordance rate of almost 90% in a blind study. This outstanding performance can be ascribed to the high porosity and wettability of the fibrous membrane and the PAN's coordination ability towards Zn 2+ . Overall, the remarkable advantages achieved with our approach lie in the easy production, on-site, and cost-effective analysis of zinc as a biomarker for clinical and forensic applications., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

In an attempt to create models of phosphodiesterases, we previously investigated bis(guanidinium) naphthols. Such metal-free anion receptors cleaved aryl phosphates and also plasmid DNA. Observed reaction rates, however, could not compete with those of highly reactive metal complexes. In the present study, we have replaced the guanidines by ethylene diamine side chains which accelerates the plasmid cleavage by compound 13 significantly (1 mM 13: t1/2=22 h). Further gains in reactivity are achieved by azo coupling of the naphthol unit. The electron accepting azo group decreases the pK a of the hydroxy group. It can also serve as a dye label and a handle for attaching DNA binding moieties. The resulting azo naphthol 17 not only nicks (1 mM 17: t1/2~1 h) but also linearizes pUC19 DNA. Although the high reactivity of 17 seems to result in part from aggregation, in the presence of EDTA azo naphthol 17 obeys first order kinetics (1 mM 17: t1/2=4.8 h), reacts four times faster than naphthol 13 and surpasses by far the former bis(guanidinium) naphthols 4 and 5., (© 2024 The Authors. ChemistryOpen published by Wiley-VCH GmbH.)

The increase in production and innovation of chemicals that humans interface with has enhanced the need for rapid toxicity testing of new and existing chemicals. This need, along with efforts to reduce animal testing, has led to the development of high-throughput bioassays typically conducted in microplates. These bioassays offer time and resource advantages over traditional animal models; however, significant chemical losses can occur in microplates. Current methods for measuring chemical losses in microplates require extensive sample preparation and highly sensitive instruments. We propose the use of fluorescence spectroscopy to measure chemical losses in high-throughput bioassays as a low resource alternative to the existing methods. A fluorescent plate reader was used to develop methods for quantifying the aqueous concentrations of two chemicals, 2-hydroxynaphthalene and acridine, in microwells of a 96-well microplate. A high-throughput, 5 day embryonic zebrafish bioassay was used as the model bioassay for method development. Chemical losses were attributed to a combination of photodegradation, sorption, and uptake by the zebrafish embryos, kinetics of which were derived from a pseudo-first order model. Chemical uptake amount was calculated to be approximately 50% and 21% of the total chemical amount added for 2-hydroxynaphthalene and acridine, respectively. Unexpected cranial deformities were observed in the embryonic zebrafish, suggesting further investigation of potential additive toxicity of the ultraviolet radiation exposure from fluorescence measurements and chemical exposure is needed. Nonetheless, this novel method provides a rapid, low resource approach to measuring chemical losses in microplates that can be extended to a variety of autofluorescent chemicals and microplate-based bioassays.

To develop ultrasensitive and rapid antibiotics residue detection method is crucial for ensuring food safety and protecting human health. Herein, a novel photoelectrochemical (PEC) aptasensor integrated with single-atom ruthenium (Ru) nanozyme-mediated catalytic precipitation as a valuable signal amplification strategy, have been established for ultrasensitive chloramphenicol (CAP) detection. Particularly, the exceptional peroxidase-mimicking activity of single-atom Ru nanozyme is responsible for accelerating the oxidation of 4-chloro-1-naphthol (4-CN) to produce insoluble precipitate on the electrode, which in turn causes a notable reduction in the photocurrent. Whereas, when CAP is present, the aptamer is liberated away the electrode because of its potent affinity with CAP, resulting in an elevation of the photocurrent signal, enhancing the detection sensitivity. Importantly, the signal amplification strategy combines the effective photoactive material of Au nanoparticles/CdS quantum dot/TiO 2 composites, a PEC aptasensor for determination of CAP with an ultralow detection limit of 4.12 pM is achieved in a self-powered mode with great selectivity and accuracy. This work proposes a novel reasonable approach utilizing high-activity single-atom nanozyme to induce signal amplification strategy for the advancement of single-atom nanozyme in ultrasensitive PEC biosensor, and further creates new avenues for ultrasensitive detection beyond antibiotics residue., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: Geosmin (GSM) can compromise the immune systems of aquatic organisms, rendering them more vulnerable to viral and bacterial infections, thereby adversely affecting their growth, reproduction, yield, and quality. Given the relatively low odor thresholds of GSM, there is a critical demand for the development of a highly sensitive and rapid detection method. According to the principle of Surface-enhanced Raman spectroscopy (SERS), localized surface plasmon resonance (LSPR) greatly enhances the Raman signals of adsorbed molecules. To date, no study has reported the application of SERS to detect GSM., Results: Dual-metal nanomaterials with hollow structures have been proven to provide a large surface area and heightened localized surface plasmon resonance, thereby enhancing the sensitivity of Raman signals. In this study, a sample-to-answer platform was constructed by integrating Au@Ag hollow nanoshells (HNSs)-based SERS and a microfluidic chip for the sensitive, fast, and direct determination of GSM. Under 532 nm excitation, GSM exhibit Raman peaks on the SERS-active Au@Ag HNSs, and there is a relationship between the peak intensity and the concentration of GSM. Owing to the integration of the microfluidic chip, only microliters of reagent are required, and the test results can be achieved within 4 min. The constructed sample-to-answer platform showed a good linear response to GSM in the range of 1 ng/L-1 mg/L, with a detection limit of 0.16 ng/L. An optimal calibration model is established by combining stoichiometric algorithms., Significance: This work realized the ultra-highly sensitive and fast determination of GSM based on SERS-active Au@Ag HNSs, which provides new insights and is very promising for the on-site monitoring of earthy odors. Our study makes a significant contribution to the literature because the developed SERS-based detection method does not require labels or biomaterials, providing the possibility of highly sensitive and on-site testing of contaminants in food and the environment., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

The residual carbaryl in crops can cause serious damage to the human kidney and nervous system after entering the human body, which may be metabolized to 1-naphthol (1-NAP) and excreted through urine. 1-NAP is often used as the biomarker for carbaryl exposure, so the intake or leakage of carbaryl can be monitored by detecting the concentration of 1-NAP. Herein, Co, N, P ternary co-doped carbon dots (CoNP-CDs) derived from vitamin B12 were synthesized by a facile hydrothermal method. CoNP-CDs exhibited oxidase-like activity and excellent peroxidase-like activity, which was attributed to the Fenton-like reaction of Co 2+ /Co 3+ and the presence of pyrrole N and P elements, which together provided multiple active sites for chromogenic substrates. Due to the dual enzyme-like activity of CoNP-CDs, hydroxyl radicals (OH) and superoxide radicals (O 2 - ) were generated during the catalytic process, which could rapidly oxidize colorless 3,3',5,5'-tetramethyl benzidine (TMB) to blue oxidation products (oxTMB). The α-carbon in 1-NAP can be attacked by OH, and the catalytic oxidation process of TMB can be inhibited by the consumption of OH, so that the blue color of the solution became lighter. Based on this principle, a smartphone-assisted colorimetric sensing platform was constructed for the detection of 1-NAP, and which resulted in a linear range of 1.07-37.3 μM and a visual detection limit of 0.68 μM. Moreover, the colorimetric sensing system showed satisfactory recoveries in the detection of human urine samples. The colorimetric sensing system owned the advantages of fast response, strong selectivity and simple operation, and provided a potential strategy for the on-site detection of 1-NAP., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

In this work a novel method for synthesis of 1,8-dihydroxynaphthalene melanin was presented, as well as the physicochemical properties, molecular structure, and characteristics of the pigment. The proposed synthesis protocol is simple and cost-effective with no enzymes or catalysts needed. The final product is not adsorbed on any surface, since the pigment is the result of autooxidation of 1,8-dihydroxynaphthalene. Performed analyses revealed that the solubility, optical and paramagnetic properties are typical for melanins, and in the EPR spectra an unusual hyperfine structure was observed. The molecular structure of the pigment consists of three different layers forming polar and non-polar surfaces. Additionally, the presence of ether bonds presence was revealed. The developed method creates new opportunities for melanin research and eliminates the need to extract melanins from biological samples, which often lead to structural changes in isolated melanins, which undermines the reliability of analyses of the properties and structure of these polymers. On the other hand, the ubiquity of melanins in living organisms and the diversity of their biological functions have let to the growing interest of researchers in this group of pigments. The analyses carried out show that the obtained synthetic DHN polymer can be considered as a model DHN-melanin in mycological studies and material research., Competing Interests: Declarations. Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

Multimodal biosensors with independent signaling pathways can self-calibrate and improve the reliability of disease biomarker detection. Herein, a colorimetric-fluorescent dual-mode paper-based biosensor with PAN/Fe(III)-CNOs (FPCs) as core components has been developed, which information is recognized by smartphone and naked eye. Using 1-(2-pyridylazo)-2-naphthol (PAN) as a mediator, Fe(III) is enriched on the surface of carbon nano-onions (CNOs), endowing FPCs with excellent mimetic enzyme activity and photothermal conversion ability, which allows it to output amplified colorimetric signals under laser irradiation. In addition, the complexation of PAN with Fe(III) broadens its absorption spectrum, which makes FPCs more suitable to be energy acceptors to quench fluorescence of polymer dots (Pdots), resulting in the changes of output fluorescent signal. Based on the above design, a portable colorimetric-fluorescent dual-mode biosensor is proposed for trypsin detection with Pdots as fluorescence sources and FPCs as fluorescence quenchers and nanoenzymes. This work provides a convenient way for constructing portable visual multimodal biosensors, which is expected to applied in various disease diagnosis., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: Nanozyme is a kind of biomimetic enzyme with unique properties and catalytic function of nanomaterials. Various nanozymes have been applied in the development of visual biosensors because of its excellent stability and availability. Nevertheless, the current applications of nanozymes primarily focus on colorimetric sensing based on color changes, which is susceptible to external factors interference including sample solution color and ambient light. Incorporating a distance-readout strategy with nanozymes presents a promising avenue for the advancement of innovative visual biosensing technologies in the future., Results: A visual electrochemiluminescence (ECL) sensor was developed by combining the distance-readout strategy with nanozymes catalyzing precipitation for the first time. The detection is based on the ECL length change induced by nanozymes. This sensor chip comprises a square detection area and a visual ECL channel area. A peroxidase-mimic, core-shell hollow Fe 3 O 4 @PDA@ZIF-67, was modified in the detection region. The substrate 4-chloro-1-naphthol was rapidly catalyzed by nanozymes to form purple precipitate benzo-4-chlorohexanedione, leading to an increase in impedance within the detection region. Consequently, the detection area's partial voltage rose while the visual channel's dropped, resulting in a shorter ECL length. As a proof-of-concept experiment, the visual distance-readout ECL sensor was utilized for the quantitative detection of H 2 O 2 . The alteration in ECL length exhibited a good linear relationship with H 2 O 2 concentration (logarithm) within the range of 300 nM to 300 μM, with the limit of detection (LOD) of 87 nM., Significance: This work developed a novel approach for the application of nanozymes in analytical chemistry. Compared with common colorimetric sensing, this method is more convenient and intuitive, which can effectively eliminate potential interference from humans and the environment during signal acquisition. Because biocatalytic precipitation can be formed through multiple sensing processes, this strategy holds great promise as a portable and cost-effective tool with diverse applications., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

1'-Hydroxy-4',8,8'-trimethoxy-[2,2'-binaphthalene]-1,4-dione (compound 5 ), a secondary metabolite recently discovered in marine fungi, demonstrates promising cytotoxic and anticancer potential. However, knowledge regarding the anticancer activities and biological mechanisms of its derivatives remains limited. Herein, a series of novel naphthoquinone-naphthol derivatives were designed, synthesised, and evaluated for their anticancer activity against cancer cells of different origins. Among these, Compound 13 , featuring an oxopropyl group at the ortho -position of quinone group, exhibited the most potent inhibitory effects on HCT116, PC9, and A549 cells, with IC 50 values decreasing from 5.27 to 1.18 μM (4.5-fold increase), 6.98 to 0.57 μM (12-fold increase), and 5.88 to 2.25 μM (2.6-fold increase), respectively, compared to compound 5 . Further mechanistic studies revealed that compound 13 significantly induced cell apoptosis by increasing the expression levels of cleaved caspase-3 and reducing Bcl-2 proteins through downregulating the EGFR/PI3K/Akt signalling pathway, leading to the inhibition of proliferation in HCT116 and PC9 cells. The present findings suggest this novel naphthoquinone-naphthol derivative may hold potential as an anticancer therapeutic lead.

The construction, structural identifications along with compositional properties, using TEM, FT-IR, and XPS spectroscopies, of an innovative light-induced multi-arm azobenzenes based Fe 3 O 4 magnetic nanoparticles (Azo-Fe 3 O 4 MNPs) are being reported. Such organic (light-sensitive dendrimers-like structure), inorganic (magnet core), hybrid material has been applied as an efficient recoverable/reusable extractive sorbent for the detection of phthalate plasticizers from acetate buffer solution. The extraction study was controlled within consecutive procedures via UV-light exposure to achieve pore-size control which then further subjected for the evaluation of the analytes' retention, separation, and release as well as the detection of the phthalate pollutants using GCMS-. Various experimental conditions, such as time of extraction, salt concentration, pH, and desorption time, were studied and adjusted. Additionally, the extraction repeatability (RSD from 0.46 % to 6.12%, n = 5) of the studied sorbent was comparable to other published work. The linear range extended from 6.25 to 100 μg L - ¹ and detection limits (LOD) within the range of 41- 150 ng L -1 were achieved, demonstrating good linearity with values ranging from 0.9992 to 0.9892. The inter-batch and intra-batch RSD ranged from 0.46 % to 6.12 %, respectively. Additionally, it provides effective detection of 2-naphthol when used as a SALDI substrate., Competing Interests: Declaration of competing interest There is NO conflict of interest regarding the publication of this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

The escalating severity of the menace posed by bacterial resistance has rendered the existing antibiotics less effective, thus necessitating the discovery of new antibacterial agents. The current study reports the exploration of substituted N-pyridinylaminonaphthols produced by a straightforward, one-pot multicomponent reaction process as antibacterial agents. The synthesized derivatives were assessed in vitro for their antibacterial properties against a panel of bacterial pathogens. The analogs 4b, 4g, 4h, 4i, 4j, 4l, 4r, and 4t exhibited potent inhibitory activity with minimum inhibitory concentration (MIC) values of 1-2 µg/mL. Notably, 4b, 4l, and 4t displayed an excellent selectivity index. Additionally, they were active against the multidrug-resistant bacterial strains, with 4l exhibiting the best activity against methicillin-resistant Staphylococcus aureus and vancomycin resistant staphylococcus aureus with a MIC of 1 µg/mL. 4l showed synergism with gentamycin and showed bactericidal property in a concentration-dependent manner. Furthermore, the molecule 4l inhibited the DNA gyrase supercoiling activity. Absorption, distribution, metabolism, excretion/toxicity parameters and pharmacokinetic properties were assessed via in silico techniques, which elucidate the potential mode of action. These findings demonstrate the potential of the N-pyridinylaminonaphthol derivatives as antibacterial agents against multidrug-resistant S. aureus., (© 2024 Deutsche Pharmazeutische Gesellschaft.)

Amino acids are important chiral compounds in the human body, and are important basic components that make up the human body and play an important role in the human body. Among them, different enantiomers of an amino acid may have different roles, and different types of amino acids can be interconverted. However, the content of D-amino acids is much lower than that of L-amino acids, which is difficult to be detected. At present, many of the potential roles of D-amino acids, such as the conversion of D-amino acids to each other, have not yet been fully revealed. Hence, we synthesized fluorescent probe (R)-5 by condensation of 1,1'-Bi-2-naphthol (BINOL) and 2-(Aminomethyl)pyridine with Schiff base, which can recognize both D-arginine and D-glutamic acid at low concentrations. Meanwhile, (R)-5 can be applied to paper-based sensors for the detection of arginine and glutamate in living cells and for food amino acid detection., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

In this work, a new supramolecular solvent (SUPRAS) was prepared for the first time using hexafluorobutanol (HFB) and farnesol (FO). FO acts as an amphiphile and HFB as a coacervation inducer and density regulator. The method of dispersive liquid-liquid microextraction followed by high-performance liquid chromatography, supported by a vortex technique, was established using the prepared SUPRAS for the determination of Sudan dyes in aqueous samples. The extraction parameters, including FO content, HFB content, vortex time, salt addition, and solution pH, were thoroughly investigated and optimized. Under the optimized conditions, the linearity range is 10-750 ng/mL for Sudan I, and 10-1000 ng/mL for Sudan III and Sudan IV, respectively. The limits of detection for Sudan dyes were in the range of 0.8-3.1 ng/mL. The inter- and intra-day relative standard deviations for Sudan dyes were in the range of 1.3%-4.1% and 0.2%-2.6%, respectively. Finally, the proposed method was applied to the determination of Sudan dyes in beverage and river water samples with recoveries ranging from 93.9% to 122.1%. Compared to conventional techniques for the extraction of Sudan dyes in real samples, the proposed method is simpler, faster, and more environmentally friendly., (© 2024 Wiley‐VCH GmbH.)

N -Nitrosamines are contaminants found throughout the environment, including in drinking water, and many nitrosamines are likely potent carcinogens. Correspondingly, there is a need for rapid and cost-effective in-field detection methods that can provide timely information about their contamination levels in water. This study details a colorimetric assay for detecting aqueous N -nitrosodimethylamine (NDMA) by photochemical nitrosation of a commercial naphtholsulfonate, to offer an attractive alternative to traditional laboratory-based analysis. The resulting naphthoquinone-oxime coordinates to aqueous iron(II) ions to form a green complex, allowing for direct visual detection. Characterization via Mössbauer and electron paramagnetic resonance (EPR) spectroscopy, alongside single-crystal structure determination, provides comprehensive structure information on the iron indicator complex. Optimization of detection conditions, including UV irradiation and response times, led to an improved colorimetric detection method with a limit of detection of 0.66 ppm for NDMA. The practical applicability and selectivity of this colorimetric detection scheme make it a promising candidate for the development of field-deployable sensors for NDMA in environmental water samples.

Macrocycles play vital roles in supramolecular chemistry and chromatography. 1,1'-Bi-2-naphthol (BINOL)-based chiral polyimine macrocycles are an emerging class of chiral macrocycles that can be constructed by one-step aldehyde-amine condensation of BINOL derivatives with other building blocks. These macrocycles exhibit good characteristics, such as facile preparation, rigid cyclic structures, multiple chiral centers, and defined molecular cavities, that make them good candidates as new chiral recognition materials for chromatographic enantioseparations. In this study, a BINOL-based [2+2] chiral polyimine macrocycle was synthesized by one-step condensation of enantiopure (S)-2,2'-dihydroxy-[1,1'-binaphthalene]-3,3'-dicarboxaldehyde with (1R,2R)-1,2-diaminocyclohexane. The product was modified with 5-bromo-1-pentene and then attached to thiolated silica using click chemistry to construct a new chiral stationary phase (CSP). The enantioselectivity of the new CSP was explored by separating various racemates under normal phase (NP) and reversed phase (RP) high performance liquid chromatography (HPLC). Thirteen racemates and eight racemates were enantioseparated under the two separation modes, respectively, including chiral alcohols, phenols, esters, ketones, amines, and organic acids. Among them, nine racemates achieved baseline separation under NP-HPLC and seven racemates achieved baseline separation under RP-HPLC. High resolution separation was observed with benzoin (Rs = 5.10), epinephrine (Rs = 4.98), 3-benzyloxy-1,2-propanediol (Rs = 4.42), and 4,4'-dimethylbenzoin (Rs = 4.52) in NP-HPLC, and with 4-methylbenzhydrol (Rs = 4.72), benzoin ethyl ether (Rs = 3.79), 1-phenyl-1-pentanol (Rs = 3.68), and 1-(3-bromophenyl)ethanol (Rs = 3.60) in RP-HPLC. Interestingly, the CSP complemented Chiralcel OD-H, Chiralpak AD-H, and CYCLOBOND I 2000 RSP columns for resolution of these test racemates, separating several racemic compounds that could not be well separated by the three commercially available columns. The influences of injected sample amount on separation were also evaluated. It was found that the column exhibited excellent stability and reproducibility after hundreds of injections, and the relative standard deviations (n = 5) of the retention time and resolution were less than 0.49% and 0.69%, respectively. This study indicates that the BINOL-based chiral macrocycle has great potential for HPLC enantioseparation., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

The present work describes a quick, simple, and efficient method based on the use of layered double hydroxides (LDH) coupled to dispersive solid phase micro-extraction (DSPME) to remove α-naphthol (α-NAP) and β-naphthol (β-NAP) isomers from water samples. Three different LDHs (MgAl-LDH, NiAl-LDH, and CoAl-LDH) were used to study how the interlayer anion and molar ratio affected the removal performance. The critical factors in the DSPME procedure (pH, LDH amount, contact time) were optimized by the univariate method under the optimal conditions: pH, 4-8; LDH amount, 5 mg; and contact time, 2.5 min. The method can be successfully applied in real sample waters, removing NAP isomers even in ultra-trace concentrations. The large volume sample stacking (LVSS-CE) technique provides limits of detections (LODs) of 5.52 µg/L and 6.36 µg/L for α-naphthol and β-naphthol, respectively. The methodology's precision was evaluated on intra- and inter-day repeatability, with %RSD less than 10% in all cases. The MgAl/Cl - -LDH selectivity was tested in the presence of phenol and bisphenol A, with a removal rate of >92.80%. The elution tests suggest that the LDH MgAl/Cl - -LDH could be suitable for pre-concentration of α-naphthol and β-naphthol in future works., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier B.V.)

Synthetic routes to geosmin and its enantiomer are well established, but the enantioselective synthesis of stereoisomers of geosmin is unknown. Here a stereoselective synthesis of all stereoisomers of geosmin is reported, yielding all compounds in high enantiomeric purity. Furthermore, the stereoselective synthesis of a geosmin derivative isolated from a mangrove associated streptomycete was performed, establishing the absolute configuration of the natural product. Finally, a new side product of the geosmin synthase from Streptomyces ambofaciens was isolated and its structure was elucidated by NMR spectroscopy. The absolute configuration of this new compound was determined through a stereoselective synthesis.

Geosmin, a ubiquitous volatile sesquiterpenoid of microbiological origin, is causative for deteriorating the quality of many foods, beverages, and drinking water, by eliciting an undesirable "earthy/musty" off-flavor. Moreover, and across species from worm to human, geosmin is a volatile, chemosensory trigger of both avoidance and attraction behaviors, suggesting its role as semiochemical. Volatiles typically are detected by chemosensory receptors of the nose, which have evolved to best detect ecologically relevant food-related odorants and semiochemicals. An insect receptor for geosmin was recently identified in flies. A human geosmin-selective receptor, however, has been elusive. Here, we report on the identification and characterization of a human odorant receptor for geosmin, with its function being conserved in orthologs across six mammalian species. Notably, the receptor from the desert-dwelling kangaroo rat showed a more than 100-fold higher sensitivity compared to its human ortholog and detected geosmin at low nmol/L concentrations in extracts from geosmin-producing actinomycetes.

The degree of the carbohydrate antigen 125 (CA-125) level in serum is positively correlated with the severity of ovarian cancer. In this study, a facile photoelectrochemical (PEC) immunoassay was devised for sensitive detection of CA-125 employing enzyme-catalyzed precipitation to weaken the photocurrent of hollow porous In 2 O 3 nanotubes incorporating CdS nanoparticles. Upon the addition of the target analyte, horseradish peroxidase (HRP) enriches as a result of the formation of the sandwich immunocomplex, which can catalyze the conversion of 4-chloro1-naphthol (4-CN) to benzo-4-chlorohexadienone (4-CD) employing H 2 O 2 as a cofactor. The as-produced insoluble precipitate acts as an obstacle to hinder the absorption of visible light by photoactive materials, thereby resulting in a decrease in photocurrent. Moreover, the weakened signal can be easily read out by a digital multimeter (DMM), advancing the convenience of the detection system. The preliminary analysis data indicate that the PEC immunoassay shows an efficient response to CA-125 levels ranging from 0.1 to 100 U mL -1 with a limit of detection (LOD) as low as 0.046 U mL -1 (S/N = 3). Most importantly, the proposed portable method has shown satisfactory performance in terms of selectivity, reproducibility, stability, and analysis in complex biological matrices.

Cysteine (Cys) plays an indispensable role as an antioxidant in the maintenance of bioredox homeostasis. We have constructed an efficient fluorescent probe Mito-Cys based on the binding of indole and naphthol. The acrylic ester group serves as a recognition switch for specific detection of Cys, which undergoes Michael addition and intramolecular cyclization reactions, thereby ensuring the chemical kinetics priority of Cys compared to other biothiols. The probe has good water solubility, large Stokes shift (137 nm), with a detection limit of 21.81 nM. In addition, cell imaging experiments have shown that the probe has excellent mitochondrial targeting ability (R = 0.902). The probe can distinguish between Cys, homocysteine (Hcy) and glutathione (GSH), and can detect Cys specifically and quickly (100 s) to ensure accurate quantitative analysis of Cys changes in cells. More importantly, the probe confirms that ferroptosis inducing factors trigger thiol starvation in mitochondria, which helps to gain a deeper understanding of the physiological and pathological functions related to Cys and ferroptosis., (© 2024. The Author(s), under exclusive licence to the European Photochemistry Association, European Society for Photobiology.)

The precise recognition and sensing of steroids, a type of vital biomolecules, hold immense practical value across various domains. In this study, we introduced corral[4]BINOLs (C[4]BINOLs), a pair of enantiomeric conjugated deep-cavity hosts, as novel synthetic receptors for binding steroids. Due to the strong hydrophobic effect of their deep nonpolar, chiral cavities, the two enantiomers of C[4]BINOLs demonstrated exceptionally high recognition affinities (up to 10 12  M -1 ) for 16 important steroidal compounds as well as good enantioselectiviy (up to 15.5) in aqueous solutions, establishing them as the most potent known steroid receptors. Harnessing their ultrahigh affinity, remarkable enantioselectivity, and fluorescence emission properties, the two C[4]BINOL enantiomers were employed to compose a fluorescent sensor array which achieved discrimination and sensing of 16 structurally similar steroids at low concentrations., (© 2024 Wiley-VCH GmbH.)

CdIn 2 S 4 and zinc tetrakis(4-carboxyphenyl)porphyrin (ZnTCPP) were synthesized by hydrothermal method, and an organic dye-sensitized inorganic semiconductor ZnTCPP/CdIn 2 S 4 type II heterojunction was constructed on a fluorine-doped tin oxide (FTO) substrate electrode. A sandwich immunostructure for signal-attenuation photoelectrochemical (PEC) detection of cardiac troponin I (cTnI) was constructed using the ZnTCPP/CdIn 2 S 4 /FTO photoanode and a horseradish peroxidase (HRP)-ZnFe 2 O 4 -Ab 2 -bovine serum albumin (BSA) immunolabeling complex. The bioenzyme HRP and the HRP-like nanozyme ZnFe 2 O 4 can co-catalyze the oxidation of 4-chloro-1-naphthol (4-CN) by H 2 O 2 to produce an insoluble precipitate on the photoanode, thus notably reducing the anodic photocurrent for quantitative determination of cTnI. Under the optimal conditions, the photocurrent at 0 V vs. SCE in 0.1 M phosphate buffer solution (pH 7.40) containing 0.1 M ascorbic acid was linear with the logarithm of cTnI concentration from 500 fg mL -1 to 50.0 ng mL -1 , and the limit of detection (LOD, S/N = 3) is 0.15 pg mL -1 . Spiked recoveries were 95.1% ~ 104% for assay of cTnI in human serum samples., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Austria, part of Springer Nature.)

Pigments such as anthraquinones (AQs) and melanins are antioxidants, protectants, or virulence factors. AQs from the entomopathogenic bacterium Photorhabdus laumondii are produced by a modular type II polyketide synthase system. A key enzyme involved in AQ biosynthesis is PlAntI, which catalyzes the hydrolysis of the bicyclic-intermediate-loaded acyl carrier protein, polyketide trimming, and assembly of the aromatic AQ scaffold. Here, multiple crystal structures of PlAntI in various conformations and with bound substrate surrogates or inhibitors are reported. Structure-based mutagenesis and activity assays provide experimental insights into the three sequential reaction steps to yield the natural product AQ-256. For comparison, a series of ligand-complex structures of two functionally related hydrolases involved in the biosynthesis of 1,8-dihydroxynaphthalene-melanin in pathogenic fungi is determined. These data provide fundamental insights into the mechanism of polyketide trimming that shapes pigments in pro- and eukaryotes., (© 2024 The Authors. Advanced Science published by Wiley‐VCH GmbH.)

(-)-Geosmin has high demand in perfumes and cosmetic products for its earthy congenial aroma. The current production of (-)-geosmin is either by distillation of sun-baked soil or by inefficient chemical synthesis because of the presence of multiple chiral centers. Fermentation processes are not viable as the titers of the Streptomyces sp. based processes are low. This work presents an alternative route by the heterologous synthesis of (-)-geosmin in Saccharomyces cerevisiae. The enzyme involved is the bifunctional geosmin synthase that catalyzes the conversion of farnesyl diphosphate to germacradienol and germacradienol to geosmin. This study evaluated the activity of many orthologs of geosmin synthase when expressed heterologously in S. cerevisiae. When the well-characterized CAB41566 from Streptomyces coelicolor origin was tested, germacradienol and germacrene D were detected but no geosmin. Bioinformatic analysis based on high/low identities to N-terminal and C-terminal domains of CAB41566 was carried out to identify different orthologs of geosmin synthase proteins from different bacterial and fungal origins. ADO68918 of Stigmatella aurantiaca origin showed the best activity among the tested orthologs, not only in terms of geosmin production but also an order of magnitude higher total abundance of the products of geosmin synthase as compared to CAB41566. This study successfully demonstrated the production of (-)-geosmin in S. cerevisiae and offers an alternative, sustainable and environment-friendly approach to producing (-)-geosmin., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

This study describes the interaction of human serum albumin (HSA) with the binol derivative (R)-(+)-3,3'-dibromo-1,1'-bi-2-naphthol (R-BrB), which has its optical activity based on the prohibitive energetic barrier for conversion into the enantiomer (S)-(+)-3,3'-dibromo-1,1'-bi-2-naphthol (S-BrB). The objective was to assess the ability of HSA to differentiate axial enantiomers based on their binding efficiency and their impact on the CD spectra. We discovered that both enantiomers were effective ligands, and the CD signal disappeared when equimolar amounts of R-BrB and S-BrB were simultaneously added, indicating no preference for either enantiomer. The complexation resulted in a significant signal increase at 250 nm and a bathochromic effect at 370 nm. Molecular docking simulations were performed, and the lower energy pose of R-BrB was selected for DFT calculations. The theoretical CD spectra of free and complexed R-BrB were obtained and showed alterations corroborating the experimental results. By comparing the difference spectrum (HSA:R-BrB minus HSA) with the spectrum of free RBrB in water or ethyl alcohol, we concluded that the CD signal intensification was due to the increased solubilization of R-BrB upon binding to HSA., (© 2024 Wiley Periodicals LLC.)

Cancer is a disease of mutation and lifestyle modifications. A large number of normal genes can transform normal cells to cancer cells due to their deregulations including overexpression and loss of expression. Signal transduction is a complex signaling process that involves multiple interactions and different functions. C-Jun N-terminal kinases (JNKs) is an important protein involved in signaling process. JNK mediated pathways can detect, integrate, and amplify various external signals that may cause alterations in gene expression, enzyme activities, and different cellular functions that affect cellular behavior like metabolism, proliferation, differentiation, and cell survival. In this study, we performed molecular docking protocol (MOE) to predict the binding interactions of some known anticancer 1-hydroxynaphthalene-2-carboxanilides candidates. A set of 10 active compounds was retrieved after initial screening on the basis of docking scores, binding energies, and number of interactions and was re-docked in the active site of JNK protein. The results were further validated through molecular dynamics simulation and MMPB/GBSA calculations. The active compounds 4p and 5 k were ranked on top. After computationally exploring interactions of 1-hydroxynaphthalene-2-carboxanilides with JNK protein, we believe compounds 4p and 5 k can serve as potential inhibitors of JNK protein. It is believed that the results of current research would help to develop novel and structurally diverse anticancer compounds that will be useful not only treat cancer but also for the medication for the other diseases caused by protein deregulation., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

A requisite to improving the taste and odor attributes of farmed fish is the availability of accurate and practical analytical methods to quantify 2-methylisoborneol (MIB) and geosmin (GSM). Solid-phase microextraction (SPME) enables reliable measurement of nanogram per liter quantities of MIB and GSM in water. In contrast, direct headspace (HS)-SPME of biological matrices with variable proximate compositions can increase bias and uncertainty in off-flavor determinations. Analytical recovery plays a crucial role in the accurate determination of MIB and GSM in fish, and this study investigates strategies to maximize and account for this recovery factor. MIB and GSM values in off-flavor catfish and trout were measured using direct HS-SPME and distillation as sample preparation techniques. Trout samples prepared by distillation yielded 10-fold higher GSM recoveries than those from direct HS-SPME (31% versus 3%). A stable isotope dilution method (SIDM) was implemented by routinely spiking samples with known quantities of deuterium-labeled MIB and GSM, allowing for the correction of sample-to-sample recovery deviations. SIDM-determined GSM values generated recoveries of 106 and 95% for direct HS-SPME and distilled trout, respectively. Aspects of the strategies and techniques presented can be incorporated into existing analytical methods to improve the accuracy and sample throughput. Particularly, routine inclusion of SIDM in the evaluation of MIB and GSM can facilitate identification of reliable practices to control off-flavors in aquaculture.

Selective labeling of the protein of interest (POI) in genetically unmodified live cells is crucial for understanding protein functions and kinetics in their natural habitat. In particular, spatiotemporally controlled installation of the labels on a POI under light control without affecting their original activity is in high demand but is a tremendous challenge. Here, we describe a novel ligand-directed photoclick strategy for spatiotemporally controlled labeling of endogenous proteins in live cells. It was realized with a designer labeling reagent skillfully integrating the photochemistries of 2-nitrophenylpropyloxycarbonyl and 3-hydroxymethyl-2-naphthol with an affinity ligand. Highly electrophilic ortho -naphthoquinone methide was photochemically released and underwent a proximity coupling reaction with nucleophilic amino acid residues on the POI in live cells. With fluorescein as a marker, this photoclick strategy enables time-resolved labeling of carbonic anhydrase subtypes localized either on the cell membrane or in the cytoplasm and a discriminable visualization of their metabolic kinetics. Given the versatility underlined by facilely tethering other functional entities (e.g., biotin, a peptide short chain) via acylation or (in cell) Huisgen cycloaddition, this affinity-driven photoclick chemistry opens up enormous opportunities for discovering dynamic functions and mechanistic interrogation of endogenous proteins in live cells.

Onoceroids are a rare family of triterpenes. One representative onoceroid is ambrein, which is the main component of ambergris used as a traditional medicine. We have previously identified the onoceroid synthase, BmeTC, in Bacillus megaterium and succeeded in creating ambrein synthase by introducing mutations into BmeTC. Owing to the structural similarity of ambrein to vitamin D, a molecule with diverse biological activities, we hypothesized that some of the activities of ambergris may be induced by the binding of ambrein to the vitamin D receptor (VDR). We demonstrated the VDR binding ability of ambrein. By comparing the structure-activity relationships of triterpenes with both the VDR affinity and osteoclastic differentiation-promoting activity, we observed that the activity of ambrein was not induced via the VDR. Therefore, some of the activities of ambergris, but not all, can be attributed to its VDR interaction. Additionally, six unnatural onoceroids were synthesized using the BmeTC reactions, and these compounds exhibited higher VDR affinity than that of ambrein. Enzymatic syntheses of onoceroid libraries will be valuable in creating a variety of bioactive compounds beyond ambergris., (© 2024. The Author(s).)

HS-1793 is a novel derivative of resveratrol, a compound known for its numerous beneficial effects, including anticancer activity, anti-inflammatory response, antimicrobial, antiaging, anti-cardiovascular disease activity, neuroprotective activity, etc. Despite its wide and interesting properties, resveratrol suffers from a crucial flaw because it is low bioavailable. For this reason, many other derivatives were explored and among them, HS-1793 has caught the attention of researchers. HS-1793 is a synthetic derivative of resveratrol discovered in 2007 that has been shown to have anti-cancer and anti-inflammatory properties. In addition, the compound showed a positive profile in metabolic processes, with adequate pharmacokinetics and pharmacodynamics. This review highlights current research on HS-1793, evaluating in vitro and in vivo works and lays the foundation for novel explorative trials in human diseases.

An increasing demand for fish products has led to an intensive aquaculture production in Brazil, and cultivation of fish constituted 860 × 10 3 tons in 2022, contributing to the 87% of total fish consumption. Nile tilapia constitutes almost half of the aquaculture production, and most tilapia farms use floating net cages. One of the major constraints of intensive fish production is production of off-flavors. Release of nutrients by the fish leads to deterioration of the water quality and stimulates growth of microorganisms, also including off-flavor producing species. The objective of this study was to determine levels of taste and odor compounds (geosmin, 2-MIB and a selection of volatile compounds) and their impact on the flavor quality of Nile tilapia produced in net cages in reservoirs in São Paulo State, Brazil. GC-MS analysis of fish and water from six different farms showed concentrations of geosmin in the water from 1 to 8 ng/L, while geosmin in fish flesh ranged from 40 to 750 ng/kg. The level of 2-MIB in water was 2 to 25 ng/L, and 0 to 800 ng/kg fish. The GC-MS analysis also revealed presence of more than 100 volatile organic compounds in the fish flesh, consisting of aldehydes, alcohols, benzene derivatives, hydrocarbons, ketones and few other compounds. Geosmin and 2-MIB related flavor notes were detected in all fish by a sensory panel, and a high correlation between the chemical and sensory analyses was found. The potential impact of the volatile organic compounds on the fish flavor is discussed. Analysis of the water quality in the reservoirs indicated that levels of geosmin and 2-MIB levels were highly influenced by the nutrient levels in the water., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Geosmin may be the most familiar volatile compound, as it lends the earthy smell to soil. The compound is a member of the largest family of natural products, the terpenoids. The broad distribution of geosmin among bacteria in both terrestrial and aquatic environments suggests that this compound has an important ecological function, for example, as a signal (attractant or repellent) or as a protective specialized metabolite against biotic and abiotic stresses. While geosmin is part of our everyday life, scientists still do not understand the exact biological function of this omnipresent natural product. This minireview summarizes the current general observations regarding geosmin in prokaryotes and introduces new insights into its biosynthesis and regulation, as well as its biological roles in terrestrial and aquatic environments., (© 2023 The Authors. Environmental Microbiology published by Applied Microbiology International and John Wiley & Sons Ltd.)

Atroposelective cross-coupling is one of the most appealing routes to construct axially chiral binaphthyl molecules due to the modular and succinct nature. Although transition-metal-catalyzed cross-couplings offer reliable synthetic means, alternative reaction modes that could be applied to broader substrate range without their pre-functionalization is highly desirable. Herein we show that the application of chiral Brønsted acid catalyst as organocatalyst could accomplish cross-coupling of 1-azonaphthalenes and 2-naphthols with high efficiency, exclusive C4-selectivity as well as excellent enantioselectivity and functional group compatibility. The identification of acylimidazolinone auxiliary for azo activating group, effective remote catalyst control and arene resonance effect synergistically play key roles in the development of this method. The utility is further demonstrated by transformations of the products into other binaphthyl compounds with perfectly retained axial chirality., (© 2023 Wiley-VCH GmbH.)

The bacterial geosmin synthase is a fascinating bifunctional enzyme that has been discovered almost two decades ago. Several aspects of the cyclisation mechanism from FPP to geosmin are known, but a detailed picture of the stereochemical course of this reaction is unknown. This article reports on a deep investigation of the mechanism of geosmin synthase through isotopic labelling experiments. Furthermore, the effects of divalent cations on geosmin synthase catalysis were investigated. The addition of cyclodextrin to enzymatic reactions, a molecule that can capture terpenes, suggests that the biosynthetic intermediate (1(10)E,5E)-germacradien-11-ol produced by the N-terminal domain is passed to the C-terminal domain not through a tunnel, but rather through release into the medium and uptake by the C-terminal domain., (© 2023 The Authors. ChemBioChem published by Wiley-VCH GmbH.)

8-hydroxyquinoline (oxine) is a widely known and frequently used chelating agent, and the pharmacological effects of the core molecule and its derivatives have been studied since the 19th century. There are several synthetic methods to modify this core. The Mannich reaction is one of the most easily implementable examples, which requires mild reaction conditions and simple chemical reagents. The three components of the Mannich reaction are a primary or secondary amine, an aldehyde and a compound having a hydrogen with pronounced activity. In the modified Mannich reaction, naphthol or a nitrogen-containing naphthol analogue (e.g., 8-hydroxyquinoline) is utilised as the active hydrogen provider compound, thus affording the formation of aminoalkylated products. The amine component can be ammonia and primary or secondary amines. The aldehyde component is highly variable, including aliphatic and aromatic aldehydes. Based on the pharmacological relevance of aminomethylated 8-hydroxyquinolines, this review summarises their syntheses via the modified Mannich reaction starting from 8-hydroxyquinoline, formaldehyde and various amines.

Naphthol hydrazone derivatives are recognized as efficient chelating agents for both qualitative and quantitative detection of metal ions. Here we design a naphthol hydrazine-based chemosensor with covalently linking a strong electron-withdrawing benzothiadiazole group to modulate the molecular electronic structure, nominated as NtHzBtd. The fluorescent probe performs excellent selectivity and sensitivity towards Fe 3+ with 1:1 binding stoichiometry, while exhibiting a quick response at 55 s with a relatively low limit of detection of 0.036 µM. A series of spectroscopic measurements in tandem with theoretical calculations suggest that the probe undergoes both intramolecular charge transfer (ICT) and chelation enhanced quenching (CHEQ) processes. Successful color rendering of paper strips and bioimaging in PC3 cells demonstrate the promising applicability of NtHzBtd for portable Fe 3+ detection in real samples and biosystems., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Hydrophobic ion pairing (HIP) can successfully increase the drug loading and control the release kinetics of ionizable hydrophilic drugs, addressing challenges that prevent these molecules from reaching the clinic. Nevertheless, polymeric nanoparticle (PNP) formulation development requires trial-and-error experimentation to meet the target product profile, which is laborious and costly. Herein, we design a preformulation framework (solid-state screening, computational approach, and solubility in PNP-forming emulsion) to understand counterion-drug-polymer interactions and accelerate the PNP formulation development for HIP systems. The HIP interactions between a small hydrophilic molecule, AZD2811, and counterions with different molecular structures were investigated. Cyclic counterions formed amorphous ion pairs with AZD2811; the 0.7 pamoic acid/1.0 AZD2811 complex had the highest glass transition temperature ( T g ; 162 °C) and the greatest drug loading (22%) and remained as phase-separated amorphous nanosized domains inside the polymer matrix. Palmitic acid (linear counterion) showed negligible interactions with AZD2811 (crystalline-free drug/counterion forms), leading to a significantly lower drug loading despite having similar log P and p K a with pamoic acid. Computational calculations illustrated that cyclic counterions interact more strongly with AZD2811 than linear counterions through dispersive interactions (offset π-π interactions). Solubility data indicated that the pamoic acid/AZD2811 complex has a lower organic phase solubility than AZD2811-free base; hence, it may be expected to precipitate more rapidly in the nanodroplets, thus increasing drug loading. Our work provides a generalizable preformulation framework, complementing traditional performance-indicating parameters, to identify optimal counterions rapidly and accelerate the development of hydrophilic drug PNP formulations while achieving high drug loading without laborious trial-and-error experimentation.

Well-known Betti bases are the products obtained by the one-pot multicomponent reaction of 1-naphthol/2-naphthol, aliphatic/aromatic aldehydes, and secondary amines, and this reaction is known as the Betti reaction. During recent years, due to the unveiling of the pharmacological and synthetic potential of Betti bases, a tremendous increase in the studies reporting novel synthetic methods for the efficient synthesis of Betti bases was observed. This review presents the recent key developments in the green synthesis of the Betti bases and accounts for the significant number of the literature reported during 2019-2022. Both catalyst free as well as the catalyst promoted synthesis (nanocatalyst, biocatalyst, transition metal catalyst, etc.) along with the synthetic applications (catalyst, ligands/chiral auxiliaries, and valuable synthons), optoelectronic applications (fluorescence sensors for phosgene gas, Hg 2+ , and Cr 3+ detection, quasi-reversible redox potential) and biological properties (anticancer agents, antioxidant, anti-inflammatory agents, antitubercular agents, pesticidal agents, anti-Alzheimer agents, Topoisomerase I inhibitors, YAP-TEAD interaction inhibitors, and DNA binding and cleavage activity) are discussed. There is a surge of interest for the development of the green and efficient Betti reaction for the construction of C-C and C-N bond in a single-step reaction accessing Betti bases as products. Along with key methodological developments for the green synthesis of Betti bases, their applications in synthetic organic chemistry, optoelectronic sensors, advanced materials synthesis, agrochemicals and pharmaceutically active scaffolds, during the period of 2019-2022, have been considered., (© 2022. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

A chiral small molecule gelator ( R )-H 3 L based on 1,1'-bi-2,2'-naphthol (BINOL)-phosphoric acid was designed and prepared, which spontaneously forms a stable water-induced gel. The gelation mechanism was revealed by single crystal X-ray diffraction analysis and a number of spectroscopic methods. Addition of Cu 2+ improved the gelation ability, and the resultant metal organic gel realized visual enantioselective and chemoselective recognition toward L-histidine from enantiomers of 19 amino acids via gel collapse. The gel showed a highly sensitive response to L-histidine, and as low as 0.01 equiv. of L-histidine relative to the critical gelation concentration of ( R )-H 3 L-Cu caused the gel to collapse. This strategy of regulating the assembly behavior through the interaction of amino acids and metal ions not only provides a simple and direct way to distinguish enantiomers, but also provides insight into how metal ions regulate the organization of biological supramolecular systems.

The enantioselective aza-Friedel-Crafts reaction is one of the most straightforward and efficient strategies for constructing a new carbon-carbon bond bearing quaternary stereocenter in organic synthesis, but the catalytic asymmetric aza-Friedel-Crafts reaction of naphthols/phenols with cyclic-ketimines attached to a neutral functional group remains still relatively unexplored. Herein, a highly enantioselective aza-Friedel-Crafts reaction of cyclic-ketimines and naphthols/phenols has been realized using a chiral phosphoric acid catalyst. A variety of chiral aminonaphthols (chiral indolin-3-ones) containing a quaternary stereocenter at the C2 position were obtained with excellent outcomes (up to 97% yield, 98% ee). Moreover, the synthetic utility of the enantiomerically enriched chiral aminonaphthols was demonstrated in some efficient transformations. According to the experimental results, a possible transition state model has been proposed to rationalize the origin of asymmetric induction.

Chiral lithium binaphtholates prepared from the corresponding binaphthols and lithium tert-butoxide effectively catalyze the asymmetric Michael additions of ketones to poorly reactive acrylamides. The lithium binaphtholate catalyst mediates ketone deprotonation and enantioselective carbon-carbon bond formation to the acrylamide to deliver the Michael adduct in good yield and enantioselectivity. A small excess of lithium tert-butoxide relative to the binaphthol successfully enolizes the ketone in the initial stage of the reaction to promote the Michael reaction. Computational analysis of the transition state suggested that the 3- and 3'-phenyl groups of the binaphtholate catalyst regulate the orientation of the lithium enolate and the subsequent approach of the acrylamide, leading to superior enantioselectivity.

The growing importance of axially chiral architectures in different scientific domains has unveiled shortcomings in terms of efficient synthetic access and skeletal variety. This account describes our strategies in answering these challenges within the organocatalytic context where the emergence of bifunctional catalysts such as chiral phosphoric acids (CPAs) has proven invaluable in controlling the sense of axial chirality. The wide occurrence of bi(hetero)aryl skeletons in privileged structures constitutes a strong motivation to devise more effective arylation methods. Our design revolves around modulating the intrinsic nucleophilicity of aromatic amines and alcohols. The first approach involves the design of an electron-withdrawing activating group which could associate with the catalyst for reactivity enhancement and selectivity control. The resonance of arenes offers the unique mechanistic possibility to select between activating sites. C2-Azo- and nitroso-substituted naphthalenes undergo atroposelective ortho C - or N -arylation with (hetero)aromatic nucleophiles. For monocyclic benzenes, programmable charge localization leads to regioselective activation by catalytic control alone or aided by substrate design. For instance, selective addition to nitroso nitrogen enables successive annulation initiated by the amine to yield axially chiral N -arylbenzimidazoles. In a biomimetic manner, a finely tuned catalyst could direct a para -selective nucleophilic approach in the atroposelective arylation of azobenzenes. The second strategy employs electrophilic arene precursors for arylation which occurs via rearomatization with central-to-axial chirality transfer. This enabled the arylation of (imino)quinones with indoles to access phenylindole atropisomers. By adapting this chemistry with an additional oxidation event to liberate the carbonyl functionalities, aryl- o -naphthoquinone and aryl- p -quinone atropisomers were attained. Along with the development of new arylation strategies, deriving new axially chiral structures has been another consistent theme of our research program. The atroposelective functionalization of alkynes provides broad entry to atropisomeric alkenes. The monofunctionalization of alkynes through the interception of an electrophilic vinylidene-quinone-methide (VQM) intermediate with 2-naphthols yielded the new EBINOL scaffolds. By designing an internal directing group, the atroposelective dihalogenation of alkynes was realized using abundant alkali halides despite their weak nucleophilicities and poor solubilities. The atroposelective N -alkylation of alkenes was pursued to prepare multifunctionalized alkene atropisomers that could be converted into 2-arylpyrroles with chirality transfer. The synthesis of B -aryl-1,2-azaborines containing a C-B chiral axis was accomplished where the CPA catalyst effects the desymmetrization and defines the configuration of the distal C-B bond. Inspired by the axially chiral scaffold of allenes, we leveraged the developed arene activation strategy to achieve para -addition and dearomatization of judiciously designed azobenzenes, which led to structurally novel cyclohexadienylidene-based hydrazones. To complement these structures, axially chiral cyclohexadienyl oxime ethers were also attained through CPA-catalyzed condensation between hydroxylamines and spiro[4.5]trienones.

Axially chiral compounds with rotationally constrained σ-bonds that exhibit atropisomerism are lucrative synthetic targets because of their ubiquity in functional materials and natural products. The metal complex-catalyzed enantioselective fabrication of axially chiral scaffolds has been widely investigated, and thus far, considerable progress has been made. Over the past two decades, we have developed a highly efficient strategy for constructing axially chiral biarenol derivatives using chiral mono- and dinuclear vanadium complexes. These complexes are readily prepared from vanadium(IV) salts and Schiff base ligands (generated from the condensation of ( S )- tert -leucine and di- or monoformyl-( R )-1,1'-bi-2-naphthol (BINOL) derivatives) under O 2 and act as highly active catalysts for highly stereoselective C-C bond formation. In particular, the vanadium complex-catalyzed enantioselective oxidative coupling of 2-naphthols 1 under oxygen or in air, which is a green oxidant, affords the desired axially chiral molecules in high yields and high stereoselectivity (up to quantitative yield and 97% ee), along with water as the sole coproduct. This coupling reaction tolerated various functional groups (such as halogens, alkoxys, and boryls) and avoided overoxidation of coupling products.The key feature of dinuclear vanadium(V) catalysts such as ( R a , S , S )- 5a is an outstanding mode of the homocoupling reaction, in which a single molecule of the catalyst activates two molecules of the starting material (e.g., 2-naphthols) simultaneously. With this "dual activation" mechanism, the oxidative coupling promoted by the dinuclear catalyst proceeds in an intramolecular manner. The homocoupling rate using 5 mol % of the dinuclear vanadium(V) complex ( R a ,S,S )- 5a was measured to be 111 times faster than that of the mononuclear vanadium(IV) complex ( S )- 4a bearing a half motif of the dinuclear vanadium complex.In the case of the heterocoupling reaction utilizing two different kinds of arenol derivatives, only a starting arenol having lower oxidation potential seems to be activated by the mononuclear vanadium complex. The reaction rate of the heterocoupling using either mono- or dinuclear vanadium complexes showed no difference to give the coupling product in high yields but with a different enantioselective manner; chiral mononuclear vanadium(V) complexes showed better enantioselectivites than that of the dinuclear vanadium(V) complexes. A competing heterocoupling study and a linear correlation between the ee of the mononucaler vanadium catalyst and ee of the heterocoupling suggested that the heterocoupling involves an intermolecular radical-anion coupling pathway.In this Account, we summarize the recent advances in vanadium-catalyzed coupling reactions that produced important chiral molecules, such as biresorcinols, polycyclic biphenols, oxa[9]helicenes, bihydroxycarbazoles, and C 1 -symmetrical biarenols, and their coupling reaction mechanisms. By pursuing vanadium catalysis, we believe numerous additional transformations as well as a renewed interest in catalytic and chemo-, regio-, and enantioselective aryl-aryl bond constructions will be manifested.

The synthesis of 2,4-disubstituted-1-naphthols has been developed employing photomediated C-C bond cleavage (UV-LED 390 nm) of cyclopropane fused-indanones generated in situ from the reaction between indenones and trimethylsulfoxonium chloride under basic conditions at room temperature. Seventeen substrates were examined in this study. The results showed that indenone precursors containing aryl substituents could smoothly provide the desired products in up to 81% yield.

The synthesis of arylamines from renewable resources under mild reaction conditions is highly desired for the sustainability of the chemical industry, where the production of hazardous waste is a prime concern. However, to date, there are very few tools in chemists' toolboxes that are able to produce arylamines in a sustainable manner. Herein, a robust one-pot approach for constructing bio-based arylamines via a combined photooxidative dearomatization-rearomatization strategy is presented. The developed methodology enables the synthesis of structurally complex amines in moderate-to-good isolated yields using biomass-derived phenols, natural α-amino acids, and naphthols under remarkably mild reaction conditions. For the photooxygenation of phenols, a novel chrysazine-based catalyst system was introduced, demonstrating its efficiency for the synthesis of natural products - hallerone, rengyolone, and the pharmaceutically relevant prodrug DHED., (© 2022 Wiley-VCH GmbH.)

This study utilized a facile one-pot protocol to synthesize Ni-cobalt zeolitic imidazolate framework (Ni-ZIF-67) nanocomposite, which was then characterized by Fourier transform infrared spectroscopy, X-ray diffraction, energy dispersive X-ray spectroscopy and scanning electron microscopy. The Ni-ZIF-67 nanocomposite was subsequently applied to modify a screen-printed electrode (SPE) as a durable sensor for detection of Sudan I concomitantly with bisphenol A (BPA), with remarkably increased electrochemical response when comparing with a bare SPE. The results showed the calibration plot to be linear in the concentration range between 0.03 μM and 535.0 μM, with a narrow limit of detection of 9.0 nM (S/N = 3). Our proposed protocol was successful in detecting target analytes in real tap water and food specimens., (Copyright © 2022. Published by Elsevier Ltd.)

A novel oxygen-containing heterocyclic linked 1H-benzo[f]chromene moieties (4a-g) and (6a-g) with anti-proliferative activity against cancer cell lines was designed, synthesized, and established on the basis of spectral data. All the prepared compounds were evaluated in vitro for their anti-proliferative activity against MCF-7, HCT-116, HepG-2 cell lines and normal cell lines HFL-1, WI-38. Compounds 4a, 4b, and 6e exhibited good activity against MCF-7, HCT-116, and HepG-2 cell lines, comparable to that of Vinblastine and Doxorubicin, and weak active against normal cell lines. Moreover, the potential mechanisms of the cytotoxic activity of the promising compounds 4a, 4b, and 6e on the more sensitive cell line MCF-7 were studied. We found that compounds 4a, 4b, and 6e induce cell cycle arrest at G2/M phases for MCF-7 treated cells compared to untreated cells, which causes apoptosis and inhibits both the topoisomerase I and II enzymes. In addition, compounds 4a and 4b exhibited comparable inhibitory activity on tyrosine kinase receptors EGFR and VEGFR-2 kinases to that of the reference protein kinases inhibitor Sorafenib. The in silico molecular docking of the most active compounds into the active sites of EGFR kinase and Topo I & II enzymes provides us with a reasonable clarification of the interpreted biological data., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Five new sesquiterpenoids, citreobenzofuran D-F ( 1 - 3 ) and phomenone A-B ( 4 - 5 ), along with one known compound, xylarenone A ( 6 ), were isolated from the culture of the mangrove-derived fungus Penicillium sp. HDN13-494. Their structures were deduced from extensive spectroscopic data, high-resolution electrospray ionization mass spectrometry (HRESIMS), and electronic circular dichroism (ECD) calculations. Furthermore, the absolute structures of 1 were determined by single-crystal X-ray diffraction analysis. Citreobenzofuran E-F ( 2 - 3 ) are eremophilane-type sesquiterpenoids with rare benzofuran frameworks, while phomenone A ( 4 ) contains a rare thiomethyl group, which is the first report of this kind of sesquiterpene with sulfur elements in the skeleton. All the compounds were tested for their antimicrobial and antitumor activity, and phomenone B ( 5 ) showed moderate activity against Bacillus subtilis, with an MIC value of 6.25 μM.

Sirtuins (SIRTs), which are nicotinamide adenine dinucleotide-dependent class III histone deacetylases, regulate cell division, survival, and senescence. Although sirtinol, a synthetic SIRT inhibitor, is known to exhibit antitumor effects, its mechanism of action is not well understood. Therefore, we aimed to assess the anticancer effects and underlying mechanism of MHY2245, a derivative of sirtinol, in HCT116 human colorectal cancer cells in vitro. Treatment with MHY2245 decreased SIRT1 activity and caused DNA damage, leading to the upregulation of p53 acetylation, and increased levels of p53, phosphorylation of H2A histone family member X, ataxia telangiectasia and Rad3-related kinase, checkpoint kinase 1 (Chk1), and Chk2. The level of the breast cancer type 1 susceptibility protein was also found to decrease. MHY2245 induced G2/M phase cell cycle arrest via the downregulation of cyclin B1, cell division cycle protein 2 (Cdc2), and Cdc25c. Further, MHY2245 induced HCT116 cell death via apoptosis, which was accompanied by internucleosomal DNA fragmentation, decreased B-cell lymphoma 2 (Bcl-2) levels, increased Bcl-2-asscociated X protein levels, cleavage of poly(ADP-ribose) polymerase, and activation of caspases -3, -8, and -9. Overall, MHY2245 induces cell cycle arrest, triggers apoptosis through caspase activation, and exhibits DNA damage response-associated anticancer effects.