Discovery of a novel class of rosmarinic acid derivatives as antibacterial agents: Synthesis, structure-activity relationship and mechanism of action.

Twenty-seven rosmarinic acid derivatives were synthesized, among which compound RA-N8 exhibited the most potent antibacterial ability. The minimum inhibition concentration of RA-N8 against both S. aureus (ATCC 29213) and MRSA (ATCC BAA41 and ATCC 43300) was found to be 6 µg/mL, and RA-N8 killed E. coli (ATCC 25922) at 3 µg/mL in the presence of polymyxin B nonapeptide (PMBN) which increased the permeability of E. coli. RA-N8 exhibited a weak hemolytic effect at the minimum inhibitory concentration. SYTOX Green assay, SEM, and LIVE/DEAD fluorescence staining assay proved that the mode of action of RA-N8 is targeting bacterial cell membranes. Furthermore, no resistance in wildtype S. aureus developed after incubation with RA-N8 for 20 passages. Cytotoxicity studies further demonstrated that RA-N8 is non-toxic to the human normal cell line (HFF1). RA-N8 also exerted potent inhibitory ability against biofilm formation of S. aureus and even collapsed the shaped biofilm.

Multi-targeting oligopyridiniums: Rational design for biofilm dispersion and bacterial persister eradication.

The development of effective antibacterial drugs to combat bacterial infections, particularly the biofilm-related infections, remains a challenge. There are two important features of bacterial biofilms, which are well-known critical factors causing biofilms hard-to-treat in clinical, including the dense and impermeable extracellular polymeric substances (EPS) and the metabolically repressed dormant and persistent bacterial population embedded. These characteristics largely increase the difficulty for regular antibiotic treatment due to insufficient penetration into EPS. In addition, the dormant bacteria are insensitive to the growth-inhibiting mechanism of traditional antibiotics. Herein, we explore the potential of a series of new oligopyridinium-based oligomers bearing a multi-biomacromolecule targeting function as the potent bacterial biofilm eradication agent. These oligomers were rationally designed to be "charge-on-backbone" that can offer a special alternating amphiphilicity. This novel and unique feature endows high affinity to bacterial membrane lipids, DNAs as well as proteins. Such a broad multi-targeting nature of molecules not only enables its penetration into EPS, but also plays vital roles in the bactericidal mechanism of action that is highly effective against dormant and persistent bacteria. Our in vitro, ex vivo, and in vivo studies demonstrated that OPc3, one of the most effective derivatives, was able to offer excellent antibacterial potency against a variety of bacteria and effectively eliminate biofilms in zebrafish models and mouse wound biofilm infection models.

Rational design of small-molecules to recognize G-quadruplexes of c-MYC promoter and telomere and the evaluation of their in vivo antitumor activity against breast cancer.

DNA G4-structures from human c-MYC promoter and telomere are considered as important drug targets; however, the developing of small-molecule-based fluorescent binding ligands that are highly selective in targeting these G4-structures over other types of nucleic acids is challenging. We herein report a new approach of designing small molecules based on a non-selective thiazole orange scaffold to provide two-directional and multi-site interactions with flanking residues and loops of the G4-motif for better selectivity. The ligands are designed to establish multi-site interactions in the G4-binding pocket. This structural feature may render the molecules higher selectivity toward c-MYC G4s than other structures. The ligand-G4 interaction studied with 1H NMR may suggest a stacking interaction with the terminal G-tetrad. Moreover, the intracellular co-localization study with BG4 and cellular competition experiments with BRACO-19 may suggest that the binding targets of the ligands in cells are most probably G4-structures. Furthermore, the ligands that either preferentially bind to c-MYC promoter or telomeric G4s are able to downregulate markedly the c-MYC and hTERT gene expression in MCF-7 cells, and induce senescence and DNA damage to cancer cells. The in vivo antitumor activity of the ligands in MCF-7 tumor-bearing mice is also demonstrated.

Chemical Biology Approach to Reveal the Importance of Precise Subcellular Targeting for Intracellular Staphylococcus aureus Eradication.

Intracellular bacterial pathogens, such as Staphylococcus aureus, that may hide in intracellular vacuoles represent the most significant manifestation of bacterial persistence. They are critically associated with chronic infections and antibiotic resistance, as conventional antibiotics are ineffective against such intracellular persisters due to permeability issues and mechanistic reasons. Direct subcellular targeting of S. aureus vacuoles suggests an explicit opportunity for the eradication of these persisters, but a comprehensive understanding of the chemical biology nature and significance of precise S. aureus vacuole targeting remains limited. Here, we report an oligoguanidine-based peptidomimetic that effectively targets and eradicates intracellular S. aureus persisters in the phagolysosome lumen, and this oligomer was utilized to reveal the mechanistic insights linking precise targeting to intracellular antimicrobial efficacy. The oligomer has high cellular uptake via a receptor-mediated endocytosis pathway and colocalizes with S. aureus persisters in phagolysosomes as a result of endosome-lysosome interconversion and lysosome-phagosome fusion. Moreover, the observation of a bacterium's altered susceptibility to the oligomer following a modification in its intracellular localization offers direct evidence of the critical importance of precise intracellular targeting. In addition, eradication of intracellular S. aureus persisters was achieved by the oligomer's membrane/DNA dual-targeting mechanism of action; therefore, its effectiveness is not hampered by the hibernation state of the persisters. Such precise subcellular targeting of S. aureus vacuoles also increases the agent's biocompatibility by minimizing its interaction with other organelles, endowing excellent in vivo bacterial targeting and therapeutic efficacy in animal models.

A Cytoplasm-Specific Fluorescent Ligand for Selective Imaging of RNA G-Quadruplexes in Live Cancer Cells.

The development of site-specific, target-selective and biocompatible small molecule ligands as a fluorescent tool for real-time study of cellular functions of RNA G-quadruplexes (G4s), which are associated with human cancers, is of significance in cancer biology. We report a fluorescent ligand that is a cytoplasm-specific and RNA G4-selective fluorescent biosensor in live HeLa cells. The in vitro results show that the ligand is highly selective targeting RNA G4s including VEGF, NRAS, BCL2 and TERRA. These G4s are recognized as human cancer hallmarks. Moreover, intracellular competition studies with BRACO19 and PDS, and the colocalization study with G4-specific antibody (BG4) in HeLa cells may support that the ligand selectively binds to G4s in cellulo. Furthermore, the ligand was demonstrated for the first time in the visualization and monitoring of dynamic resolving process of RNA G4s by the overexpressed RFP-tagged DHX36 helicase in live HeLa cells.

Novel Matrine Derivatives as Potential Larvicidal Agents against Aedes albopictus: Synthesis, Biological Evaluation, and Mechanistic Analysis.

A large number of studies have shown that matrine (MA) possesses various pharmacological activities and is one of the few natural, plant-derived pesticides with the highest prospects for promotion and application. Fifty-eight MA derivatives were prepared, including 10 intermediates and 48 target compounds in 3 series, to develop novel mosquitocidal agents. Compounds 4b, 4e, 4f, 4m, 4n, 6e, 6k, 6m, and 6o showed good larvicidal activity against Aedes albopictus, which is both a highly aggressive mosquito and an important viral vector that can transmit a wide range of pathogens. Dipping methods and a bottle bioassay were used for insecticidal activity evaluation. The LC50 values of 4e, 4m, and 6m reached 147.65, 140.08, and 205.79 µg/mL, respectively, whereas the LC50 value of MA was 659.34 µg/mL. Structure-activity relationship analysis demonstrated that larvicidal activity could be improved by the unsaturated heterocyclic groups introduced into the carboxyl group after opening the D ring. The MA derivatives with oxidized N-1 lost their mosquitocidal activities, indicating that the bareness of N-1 is crucial to maintain their anti-mosquito activity. However, the activity was not greatly influenced by introducing a cyan group at C-6 or a benzene sulfonyl group at N-16. Additionally, compounds 4e and 4m exhibited good inhibitory activities against acetylcholinesterase with inhibitory rates of 59.12% and 54.30%, respectively, at a concentration of 250 µg/mL, whereas the inhibitory rate of MA was 9.88%. Therefore, the structural modification and mosquitocidal activity of MA and its derivatives obtained here pave the way for those seeking strong mosquitocidal agents of plant origin.

Novel quinoline-based derivatives as the PqsR inhibitor against Pseudomonas aeruginosa PAO1.

AIMS: The emerging of drug resistant Pseudomonas aeruginosa is a critical challenge and renders an urgent action to discover innovative antimicrobial interventions. One of these interventions is to disrupt the pseudomonas quinolone signal (pqs) quorum sensing (QS) system, which governs multiple virulence traits and biofilm formation. This study aimed to investigate the QS inhibitory activity of a series of new PqsR inhibitors bearing a quinoline scaffold against Ps. aeruginosa. METHODS AND RESULTS: The results showed that compound 1 suppressed the expression of QS-related genes and showed the best inhibitory activity to the pqs system of wild-type Ps. aeruginosa PAO1 with an IC50 of 20.22 µmol L-1 . The virulence factors including pyocyanin, total protease, elastase and rhamnolipid were significantly suppressed in a concentration-dependent manner with the compound. In addition, compound 1 in combination with tetracycline inhibited synergistically the bacterial growth and suppressed the biofilm formation of PAO1. The molecular docking studies also suggested that compound 1 could potentially interact with the ligand-binding domain of the Lys-R type transcriptional regulator PqsR as a competitive antagonist. CONCLUSIONS: The quinoline-based derivatives were found to interrupt the quorum sensing system via the pqs pathway and thus the production of virulence factors was inhibited and the antimicrobial susceptibility of Ps. aeruginosa was enhanced. SIGNIFICANCE AND IMPACT OF STUDY: The study showed that the quinoline-based derivatives could be used as an anti-virulence agent for treating Ps. aeruginosa infections.

Novel 18ß-glycyrrhetinic acid derivatives as a Two-in-One agent with potent antimicrobial and anti-inflammatory activity.

18ß-glycyrrhetinic acid (GA) is a well-known natural compound of oleanane-type triterpene and is found possessing antimicrobial and anti-inflammatory properties. Nonetheless, its relatively low bioactivity restricts its potential in pharmaceutical applications. To maximize the potential use of this natural herbal compound as antimicrobial and anti-inflammatory agents, the rational modification of GA to enhance its pharmacological activity with low toxicity and to understand the mechanism of action is critically essential. We reported herein the design and synthesis of a series of new GA derivatives. The antimicrobial activities of these new compounds were evaluated by inhibition zone test and minimum inhibitory concentration (MIC) assay. In addition, the anti-inflammatory activity was evaluated by LPS induced BV2 cells inflammation model and 12-O-tetradecanoyl phorbol-13-acetate (TPA) induced ear inflammation mice model. It was found that the derivatives functionalized with a di-substituted phenyl group at the 2-position of GA generally displayed high antimicrobial activity against Gram-positive bacteria (MIC down to 2.5 µM) and potent anti-inflammatory effects (inhibition of NO production up to 55%, comparable to dexamethasone). The in vitro and in vivo results also showed that GA-O-02 and GA-O-06 exert their anti-inflammatory activities through downregulation of NO, pro-inflammatory cytokines and chemokines (IL-1ß, IL-6, IL-12, TNF-α, MCP-1 and MIP-1α) and upregulation of anti-inflammatory cytokines (IL-10). The anti-inflammatory mechanism may involve the inhibition of NF-κB, MAPKs and PI3K/Akt related inflammatory signaling pathways and activation of Nrf2/HO-1 signaling pathway. The results demonstrated that GA-O-02 and GA-O-06 possess great application potential as potent antimicrobial and anti-inflammatory agents.

Induction of Apoptosis via Inactivating PI3K/AKT Pathway in Colorectal Cancer Cells Using Aged Chinese Hakka Stir-Fried Green Tea Extract.

Food extract supplements, with high functional activity and low side effects, play a recognized role in the adjunctive therapy of human colorectal cancer. The present study reported a new functional beverage, which is a type of Chinese Hakka stir-fried green tea (HSGT) aged for several years. The extracts of the lyophilized powder of five HSGT samples with different aging periods were analyzed with high-performance liquid chromatography. The major components of the extract were found to include polyphenols, catechins, amino acids, catechins, gallic acid and caffeine. The tea extracts were also investigated for their therapeutic activity against human colorectal cancer cells, HT-29, an epithelial cell isolated from the primary tumor. The effect of different aging time of the tea on the anticancer potency was compared. Our results showed that, at the cellular level, all the extracts of the aged teas significantly inhibited the proliferation of HT-29 in a concentration-dependent manner. In particular, two samples prepared in 2015 (15Y, aged for 6 years) and 2019 (19Y, aged for 2 years) exhibited the highest inhibition rate for 48 h treatment (cell viability was 50% at 0.2 mg/mL). Further, all the aged tea extracts examined were able to enhance the apoptosis of HT-29 cells (apoptosis rate > 25%) and block the transition of G1/S phase (cell-cycle distribution (CSD) from <20% to >30%) population to G2/M phase (CSD from nearly 30% to nearly 10%) at 0.2 mg/mL for 24 h or 48 h. Western blotting results also showed that the tea extracts inhibited cyclin-dependent kinases 2/4 (CDK2, CDK4) and CylinB1 protein expression, as well as increased poly ADP-ribose polymerase (PRAP) expression and Bcl2-associated X (Bax)/B-cell lymphoma-2 (Bcl2) ratio. In addition, an upstream signal of one of the above proteins, phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT) signalling, was found to be involved in the regulation, as evidenced by the inhibition of phosphorylated PI3K and AKT by the extracts of the aged tea. Therefore, our study reveals that traditional Chinese aged tea (HSGT) may inhibit colon cancer cell proliferation, cell-cycle progression and promoted apoptosis of colon cancer cells by inactivating PI3K/AKT signalling.

The study of 9,10-dihydroacridine derivatives as a new and effective molecular scaffold for antibacterial agent development.

The emergence of worldwide spreading drug-resistant bacteria has been a serious threat to public health during the past decades. The development of new and effective antibacterial agents to address this critical issue is an urgent action. In the present study, we investigated the antibacterial activity of two 9,10-dihydroacridine derivatives and their mechanism. Both compounds were found possessing strong antibacterial activity against some selected Gram-positive bacteria including MRSA, VISA and VRE. The biological study suggests that the compounds promoted FtsZ polymerization and also disrupted Z-ring formation at the dividing site and consequently, the bacterial cell division is interrupted and causing cell death.

The in vitro and in vivo study of oleanolic acid indole derivatives as novel anti-inflammatory agents: Synthesis, biological evaluation, and mechanistic analysis.

Oleanolic acid (OA) is a well-known natural product possessing many important pharmacological activities; however, its weak bioactivities significantly restrict the potential application in drug development. The structural modification of oleanolic acid is an effective mean to enhance its bioactivity with lower toxicity but it is challenging. In the present study, we systematically synthesized a series of new 11-oxooleanolic acid derivatives and evaluated their anti-inflammatory activities with a LPS induced BV2 cells inflammation model and a 12-O-tetradecanoyl phorbol-13-acetate (TPA) induced ear inflammation mice model. It was found that compounds 8 and 9 show more potent anti-inflammatory effects than OA and exhibit a low cytotoxicity. The possible mechanism of action was also investigated. The in vitro and in vivo results revealed that these two new 11-oxooleanolic acid derivatives may exert anti-inflammatory activities through the inhibition of NO, pro-inflammatory cytokines and chemokines (IL-1ß, IL-6, IL-12, TNF-α, MCP-1 and MIP-1α) and upregulation of anti-inflammatory cytokines (IL-10), which may be caused by inhibiting the activation of NF-κB, MAPKs and PI3K/Akt related inflammatory signaling pathways and the activation of Nrf2/HO-1 signaling pathway. The results suggest that these two 11-oxooleanolic acid derivatives may be potential candidates for further anti-inflammatory drug development and our study demonstrated an important and practical strategy for drug discovery through the rational modification of natural products.

The study of citrus-derived flavonoids as effective bitter taste inhibitors.

BACKGROUND: The pericarp of citrus in rutaceae is rich in flavonoids that may possess diverse biological activities. Some citrus flavonoids have been used as natural bitterness inhibitors; however, many citrus flavonoid analogues that possess merit taste amelioration functions have not been reported with respect to utilization in food industry. RESULTS: The effects of 12 citrus flavonoids on the inhibition of the bitter taste of naringin, quinine hydrochloride and stevioside were evaluated both by a sensory panel and electronic tongue analysis. Among the flavonoid compounds evaluated, both neohesperidin dihydrochalcone (NHDC) and neodiosmin were identified to show an excellent bitterness inhibition effect on all three bitterness vehicles tested. The results of the electronic tongue evaluation also showed that the addition of neodiosmin, NHDC or hesperidin dihydrochalcone-7-o-glucoside (HDC-7-G) was able to reduce significantly the bitterness response value of quinine hydrochloride, which is consistent with the sensory panel evaluation. Structure-activity relationship analysis found that the 7-linked neohesperidosyloxy group in the A-ring of the citrus flavonoid skeleton has the best bitterness inhibition effect. In addition, a ternary mixture of NHDC, neodiosmin and naringin, and neodiosmin/ß-cyclodextrin was formulated and it demonstrated, for the first time in the flavor improvement of citrus fruit wine, an enhancement of sweetness and a reduction of bitter taste. CONCLUSION: Twelve citrus flavonoids were found to inhibit the bitter taste of naringin, quinine hydrochloride and stevioside. With respect to the structure-activity relationship analysis, it was found that the 7-linked neohesperidosyloxy group in the A-ring of the citrus flavonoid skeleton possessed the best bitterness inhibition effect. © 2021 Society of Chemical Industry.

Synthesis of fluorescent G-quadruplex DNA binding ligands for the comparison of terminal group effects in molecular interaction: Phenol versus methoxybenzene.

A number of new fluorescent nucleic acid binding ligands were synthesized by utilizing the non-specific thiazole orange dye as the basic scaffold for molecular design. Under simple synthetic conditions, the molecular scaffold of thiazole orange bridged with a terminal side-group (phenol or methoxybenzene) becomes more flexible because the newly added ethylene bridge is relatively less rigid than the methylene of thiazole orange. It was found that these molecules showed better selectivity towards G-quadruplex DNA structure in molecular interactions with different type of nucleic acids. The difference in terms of induced DNA-ligand interaction signal, selectivity, and binding affinity of the ligands with the representative nucleic acids including single-stranded DNA, double-stranded DNA, telomere and promoter G4-DNA and ribosomal RNA were investigated. The position of the terminal methoxyl groups was found showing strong influence both on binding affinity and fluorescent discrimination among 19 nucleic acids tested. The ligand with a methoxyl group substituted at the meta-position of the styryl moiety exhibited the best fluorescent recognition performance towards telo21 G4-DNA. A good linear relationship between the induced fluorescent binding signal and the concentration of telo21 was obtained. The comparison of ligand-DNA interaction properties including equilibrium binding constants, molecular docking, G4-conformation change and stabilization ability for G4-structures was also conducted. Two cancer cell lines (human prostate cancer cell (PC3) and human hepatoma cell (hepG2)) were selected to explore the inhibitory effect of the ligands on the cancer cell growth. The IC50 values obtained in the MTT assay for the two cancer cells were found in the range of 3.4-10.8 µM.

Hydrophobic substituents on isatin derivatives enhance their inhibition against bacterial peptidoglycan glycosyltransferase activity.

Moenomycin A, the well-known natural product inhibitor of peptidoglycan glycosyltransferase (PGT), is a large amphiphilic molecule of molecular mass of 1583 g/mol and its bioavailablity as a drug is relatively poor. In searching for small-molecule ligands with high inhibition ability targeting the enzyme, we found that the addition of hydrophobic groups to an isatin-based inhibitor of bacterial PGT significantly improves its inhibition against the enzyme, as well as its antibacterial activity. The improvement in enzymatic inhibition can be attributed to a better binding of the small molecule inhibitor to the hydrophobic region of the membrane-bound bacterial cell wall synthesis enzyme and the plasma membrane. In the present study, a total of 20 new amphiphilic compounds were systematically designed and the relationship between molecular hydrophobicity and the antibacterial activity by targeting at PGT was demonstrated. The in vitro lipid II transglycosylation inhibitory effects (IC50) against E. coli PBP1b and MICs of the compounds were investigated. Optimized results including MIC values of 6 µg/mL for MSSA, MRSA, B. subtilis and 12 µg/mL for E. coli were obtained with an isatin derivative 5m which has a molecular mass of 335 g/mol.

In situ deposition of MOF-74(Cu) nanosheet arrays onto carbon cloth to fabricate a sensitive and selective electrocatalytic biosensor and its application for the determination of glucose in human serum.

A new electrocatalytic biosensor (MOF-74(Cu) NS-CC) based on the in situ deposition of MOF-74(Cu) nanosheet on carbon cloth via a bottom-up synthetic approach in a glass tube was developed. The electrocatalytic activity of the deposited MOF-74(Cu) NS was demonstrated in the oxidation of glucose to gluconate under alkaline conditions. The results revealed that the proposed method of in situ formation of MOF-74(Cu) NS onto a carbon cloth surface in a multi-layer solution is capable to generate a stable MOF-74(Cu) NS-CC electrode with excellent sensing performance. When the as-synthesized MOF-74(Cu) NS-CC was applied directly as the working electrode for glucose sensing, it showed much higher conductivity and redox activity than MOF-74(Cu) NS-GCE. With the potential applied at 0.55 V (vs. Ag/AgCl), this new electrocatalytic biosensor exhibits an excellent linear relationship between current density and concentration of glucose. Moreover, a wide linear range of detection (1.0 to 1000 µM) was observed. The limit of detection was found to be 0.41 µM (S/N = 3). The response sensitivity is 3.35 mA mM-1 cm-2 when the concentration of glucose is in the range 1-100 µM and 3.81 mA mM-1 cm-2 for the 100-1000 µM concentration range. This study provides a low-cost, easy to prepare, and reproducible methodology for the synthesis of highly redox-active nanomaterials based on the in situ formation of two-dimensional MOF-74(Cu) NS for the development of new electrocatalytic biosensors. Graphical abstract.

Antibacterial activity of indolyl-quinolinium derivatives and study their mode of action.

Filamenting temperature-sensitive mutant Z (FtsZ) is recognized as a promising target for new antibiotics development because of its high conservatism and pivotal role in the bacteria cell division. The aromatic heterocyclic scaffold of indole is known showing merit medical functions in antiviral and antimicrobial. In the present study, a series of 1-methylquinolinium derivatives, which were integrated with an indole fragment at its 2-position and a variety of amino groups (cyclic or linear, mono- or di-amine) at the 4-position were synthesized and their antibacterial activities were evaluated. The results of antibacterial study show that the representative compounds can effectively inhibit the growth of testing strains including MRSA and VRE, with MIC values of 1-4 µg/mL by bactericidal mode. The mode of action assays revealed that c2 can effectively disrupt the rate of GTP hydrolysis and dynamic polymerization of FtsZ, and thus inhibits bacterial cell division and then causes bacterial cell death. In addition, the result of resistance generation experiment reveals that c2 is not likely to induce resistance in S. aureus.

Probing the benzofuroquinolinium derivative as a potent antibacterial agent through the inhibition of FtsZ activity.

A benzofuroquinolinium derivative that exhibits excellent cell division inhibitory effect was discovered through cell-based screening approach. This compound possesses potent antimicrobial activity against both Gram-positive and Gram-negative bacteria including the drug-resistant strains. In addition, this compound is able to restore MRSA susceptibility to beta-lactam antibiotics. The biochemical results suggest that the compound inhibits bacterial cell division through the disruption of GTPase activity and the polymerization of FtsZ, which is probably the mechanism of antibacterial activity.

Combined Chemical Activation and Fenton Degradation to Convert Waste Polyethylene into High-Value Fine Chemicals.

Plastic waste is a valuable organic resource. However, proper technologies to recover usable materials from plastic are still very rare. Although the conversion/cracking/degradation of certain plastics into chemicals has drawn much attention, effective and selective cracking of the major waste plastic polyethylene is extremely difficult, with degradation of C-C/C-H bonds identified as the bottleneck. Pyrolysis, for example, is a nonselective degradation method used to crack plastics, but it requires a very high energy input. To solve the current plastic pollution crisis, more effective technologies are needed for converting plastic waste into useful substances that can be fed into the energy cycle or used to produce fine chemicals for industry. In this study, we demonstrate a new and effective chemical approach by using the Fenton reaction to convert polyethylene plastic waste into carboxylic acids under ambient conditions. Understanding the fundamentals of this new chemical process provides a possible protocol to solve global plastic-waste problems.

A Multifunctional Bimetallic Molecular Device for Ultrasensitive Detection, Naked-Eye Recognition, and Elimination of Cyanide Ions.

A new bimetallic Fe(II) -Cu(II) complex was synthesized, characterized, and applied as a selective and sensitive sensor for cyanide detection in water. This complex is the first multifunctional device that can simultaneously detect cyanide ions in real water samples, amplify the colorimetric signal upon detection for naked-eye recognition at the parts-per-million (ppb) level, and convert the toxic cyanide ion into the much safer cyanate ion in situ. The mechanism of the bimetallic complex for high-selectivity recognition and signaling toward cyanide ions was investigated through a series of binding kinetics of the complex with different analytes, including CN(-) , SO4 (2-) , HCO3 (-) , HPO4 (2-) , N3 (-) , CH3 COO(-) , NCS(-) , NO3 (-) , and Cl(-) ions. In addition, the use of the indicator/catalyst displacement assay (ICDA) is demonstrated in the present system in which one metal center acts as a receptor and inhibitor and is bridged to another metal center that is responsible for signal transduction and catalysis, thus showing a versatile approach to the design of new multifunctional devices.

Sensitive and selective detection of uracil-DNA glycosylase activity with a new pyridinium luminescent switch-on molecular probe.

Uracil-deoxyribonucleic acid glycosylase (UDG) is known to function as an important base-excision repair enzyme and eliminate uracil from DNA molecules to maintain genomic integrity. A new small organic molecule (DID-VP) with interesting structural properties was synthesized as a G-quadruplex selective ligand and was demonstrated to be a sensitive luminescent switch-on probe in a convenient luminescent assay specifically for UDG detection in fetal bovine serum samples under rapid and simple conditions. This newly developed analytical method is based on the UDG enzymatic activity to unwind a duplex DNA substrate, and comprises a G-quadruplex-forming sequence (ON1) and uracil-containing DNA strand (ON2) to generate a remarkable fluorescence signal through the specific interaction of DID-VP with ON1. This luminescent switch-on assay is able to achieve high sensitivity and specificity for UDG over other enzymes. The application range of the present analytical system is found to be 0.05 to 1.00 U mL(-1) UDG with a very low detection limit of 0.005 U mL(-1). The recovery study of UDG in real samples gave a very good performance with 75.05%-102.7% recovery. In addition, an extended application of the assay in screening of UDG inhibitors is demonstrated. A good dose-dependence of the luminescence response with respect to the concentration of UDG inhibitors in samples was observed.