•A flexible amine-functionalized triphenylamine derivative was developed.•Significant “light-up” effect was observed when the dye bound with G4 DNAs.•The G4-targeting dye displayed excellent selectivity, sensitivity, and stability.•The cellular application in cancer cells was demonstrated.In this study, a flexible amine-functionalized triphenylamine dye 2 was developed and utilized as a G4 DNA fluorescent probe. The selectivity, sensitivity and binding properties of the dye 2 interacting with G4 DNAs were investigated. The dye 2 illustrated in the fluorescence titration assays were preferentially bound with G4 DNAs with significant “light-up” effect. The detection limit value of 2 for the G4 DNA was below 10 nM in solution. CD spectroscopy analysis revealed that 2 could promote the G-rich sequence to adapt an antiparallel G4 structure. These results indicated the dye 2 showed stronger binding affinity and fluorescence response to G4 DNA than our previous reported triphenylamine-quinolinium scaffold (1b) due to the incorporation of a flexible amine moiety. Therefore, this study gave certain crucial factors on developing of effective fluorescence probes for G4 DNA. The cellular application of 2 in cancer cells HepG2 was also demonstrated.

•A light-up fluorescent probe 1b for HRAS G-quadruplex DNA was developed.•1b could selective discrimination HRAS G-quadruplex structure over other DNA forms.•The detail interactions of BASQ with HRAS were investigated.•The cellular application in living cells was demonstrated.The development of small-molecule G-quadruplex DNA probes has attracted significant attention in recent years. However, G-quadruplexes can display a wide variety of topologies, which process different structures and functions. Therefore, selective discrimination one G-quadruplex structure over another is promising. Herein, we reported the design, synthesis and biological evaluation of a long-chain fatty amine functionalized triphenylamine-quinolinium conjugate 1b. Significant enhancement of the fluorescence intensity (over 180 fold) was observed when 1b bound with HRAS G-quadruplex DNA, while much weaker enhancements were presented in the presence of other G-quadruplexes (45–90-fold) and single/double-stranded DNAs (less than 20-fold), indicating 1b had an excellent selectivity to HRAS. The details of the interactions were investigated by UV–Vis, FID and CD analysis. The results show 1b could interact and stabilize HRAS structure mainly by π-π stacking binding mode. The introduced amine chain of the structure core was found to be better in the terms of inducing selectivity toward G-quadruplex structure. In addition, the application of 1b as a fluorescent agent for living cell imaging was also demonstrated.Download high-res image (65KB)Download full-size image

A series of novel naphthalimide-derived metronidazoles as new type of antimicrobial agents were for the first time designed, synthesized and characterized by NMR, IR and HRMS spectra. Experimental results revealed that most of them displayed moderate to good antibacterial activity towards Gram-positive and negative bacteria. Especially, compound 7b was able to not only exhibit effective inhibition towards the growth of P. vulgaris (MIC = 0.002 μmol/mL) and S. dysenteriae (MIC = 0.01 μmol/mL), but also have rapidly killing effect and prevent the development of bacterial resistance. Further research revealed that the highly active molecule 7b could not only intercalate into calf thymus DNA to form a steady supramolecular complex and thus might block DNA replication to exert the powerful bioactivities, but also be effectively transported by human serum albumin (HSA) via the formation of the 1:1 supramolecular complex, in which hydrogen bonds and hydrophobic effect played important roles in the association of compound 7b with HSA. Molecular docking indicated that the supramolecular interactions between 7b and topoisomerase II were driven by hydrogen bonds.Download high-res image (229KB)Download full-size imageA series of novel naphthalimide-derived metronidazoles as new antibacterial agents were developed. Relational supramolecular interactions with DNA, human serum albumin and topoisomerase II were investigated for the evaluation of antibacterial potentiality.

A series of novel Schiff base-bridged tetrahydroprotoberberine (THPB) triazoles were designed, synthesized and characterized for the first time. Antimicrobial assay showed that some of the prepared compounds exerted stronger antibacterial and antifungal activities than the reference drugs. Especially, THPB triazole 7a gave low MIC values of 0.5, 1 and 2 μg mL−1 against B. yeast, M. luteus and MRSA, respectively. Further experiments indicated that the highly active molecule 7a was able to rapidly kill the MRSA strain and did not trigger the development of bacterial resistance even after 14 passages. The preliminary exploration for the antimicrobial mechanism revealed that compound 7a could effectively intercalate into calf thymus DNA to form a 7a–DNA supramolecular complex, and its Zn2+ complex had the ability to directly cleave pUC19 DNA, which suggested that compound 7a might be a potentially dual-targeting antibacterial molecule. It was also found that compound 7a could be efficiently stored and carried by human serum albumin (HSA), and the hydrophobic interactions and hydrogen bonds played important roles in the transportation of HSA to the active molecule 7a.

•Prepared quinolones gave strong antimicrobial activity and broad spectrum.•Some compounds exhibited strong anti-MRSA activity.•Inducing bacterial resistance by target compound was much slower than clinical drugs.•Molecular modeling with DNA rationalized the high antibacterial activity.•Interactions of compound and DNA indicated a possible interaction mechanism.A series of novel benzimidazole quinolones as potential antimicrobial agents were designed and synthesized. Most of the prepared compounds exhibited good or even stronger antimicrobial activities in comparison with reference drugs. The most potent compound 15m was membrane active and did not trigger the development of resistance in bacteria. It not only inhibited the formation of biofilms but also disrupted the established Staphylococcus aureus and Escherichia coli biofilms. It was able to inhibit the relaxation activity of E. coli topoisomerase IV at 10 μM concentration. Moreover, this compound also showed low toxicity against mammalian cells. Molecular modeling and experimental investigation of compound 15m with DNA suggested that this compound could effectively bind with DNA to form a steady 15m-DNA complex which might further block DNA replication to exert the powerful bioactivities.A novel series of membrane active quinolone benzimidazoles were synthesized and screened for their antimicrobial activities. Molecular modeling and experimental investigation with DNA suggested the possible antibacterial mechanism.

•A hydroxyethyl-functionalized triphenylamine derivative was developed.•Significant ‘light-up’ effect was observed when this probe bound with G4 DNAs.•The G4-targeting probe displayed excellent selectivity, and sensitivity.•The cellular application in cancer cells was demonstrated.G-quadruplex (G4) DNAs have attracted considerable interest because of their important biological functions and medical applications. Searching for highly specific binding molecules is important for the basic research of G4 DNA, as well as the design of novel anticancer drugs. Previous, we have developed a quinolone-substituted triphenylamine probe (TPA-2b) with selectivity to G4 DNAs. Herein, we further designed and synthesized a hydroxyethyl functionalized derivative (TPA-3) and investigated the interactions with G4 DNAs and living cells. TPA-3 was found to express significant fluorescence enhancement upon its interaction with G4 DNAs while shows almost no response to non-quadruplex DNAs. The distinction can even be easily distinguished by the naked eye under UV light. The spectral analysis showed TPA-3 bound to G4 DNAs mainly through intercalative binding mode. CD study results indicated TPA-3 did not disturb the conformation of G4 structure. Cellular uptake assay suggested that TPA-3 could pass through membrane and enter living cells. Our results suggested the side chain of core structure could change the binding affinity to G4 DNAs, as well as the interaction with living cells. Thus, this study gives some clues to design new G4 DNA probes with high selectivity, sensitivity, and biological imaging applications.

The detection of protein/small molecule interactions plays important roles in drug discovery and protein/metabolite interactions in biology. In this work, by coupling the terminal protection of small molecule-linked ssDNA strategy with the unmodified and positively charged gold nanoparticle ((+)AuNP) nanoprobes, we have developed a sensitive and simple colorimetric sensor for the detection of folate receptor, a highly expressed protein in many kinds of malignant tumors. The target folate receptor binds the folate moieties of the folate-linked ssDNA through high affinity interactions and protects the protein-bound ssDNA from digestion by exonuclease I. The protected ssDNA thus adsorbs the ((+)AuNP) through electrostatic interactions, leading to a red-to-blue color change of the sensing solution for sensitive colorimetric detection of folate receptor at the sub-nanomolar level. Besides, this colorimetric sensor shows high selectivity toward folate receptor against other control proteins. The developed sensor avoids the modification/conjugation of the AuNP nanoprobes and the involvement of any expensive instruments for signal transduction in protein detection. Featured with these obvious advantages, the colorimetric sensor strategy demonstrated herein can be easily expanded for sensitive and convenient detection of various protein/small molecule interactions.

•The activity and stability were dependent on the reaction temperature.•Ni/SiO2 catalyst showed the best initial activity at 700 °C.•The thinnest and densest whisker carbon formed at 700 °C.•The catalyst showed the highest catalytic stability at 550 °C.•The proportion of the defective carbon reduced with increased reaction temperature.The activity and stability of Ni/SiO2 catalyst for the decomposition of methane at different temperature were investigated and the types of deposited carbon were also monitored. The catalyst was prepared by impregnation method and characterized by XRD, TG, SEM, Raman, TPH and TPO techniques. The dependence of the morphology, structure, and amount of deposited carbon over the used catalyst on the reaction temperature was studied. The results suggested that the Ni/SiO2 catalyst showed the best initial catalytic activity at 700 °C for the catalytic decomposition of methane, where the carbon whisker was the finest and densest, and the proportion of the well-ordered graphic was enhanced with increased reaction temperature. The largest amount of carbon deposition was observed at 550 °C used catalyst, and at this reaction temperature the Ni/SiO2 catalyst showed relatively the highest stability.Over 550 °C used catalyst, the thick whisker-like deposited carbon formed might keep the surface Ni species exposed, and therefore kept a better stability and activity, thus, the largest amount of carbon deposition was observed.

In this Letter, three triphenylamine-based dyes (TPA-1, TPA-2a and TPA-2b) with donor–bridge–acceptor (D–π–A) structure were designed and synthesized for the purpose of G-quadruplexes recognition. In aqueous conditions, the interactions of the dyes with G-quadruplexes were studied with the aim to establish the influence of the geometry of the dyes on their binding and probing properties. Results indicate that TPA-2b displays significant selective colorimetric and fluorescent changes upon binding of G-quadruplex DNA. More importantly, its distinct color change enables visual detection and differentiation of G-quadruplexes from single and duplex DNA structures. CD titration date reveals that TPA-2b could induce and stabilize the formation of G-quadruplex structure. All these remarkable properties of TPA-2b suggest that it should have promising application in the field of G-quadruplexes research.A colorimetric and fluorescent dual probe with D–π–A structure for G-quadruplexes was successfully developed. Its significant and distinct changes in color enable the label-free and visual detection of and differentiation of G-quadruplexes from single and duplex DNA structures.

•A series of novel cyclen compounds appending different azoles were synthesized.•Dinuclear complexes displayed broad spectrum antimicrobial activities.•The metal ions enhanced the antimicrobial activities in varying degrees.•The in vitro safeties of these promising dinuclear compounds were confirmed.A series of novel compounds containing 1,4,7,10-tetraazacyclododecane and azoles were synthesized and characterized by 1H NMR, MS and elemental analysis. Bioactive assay manifested that some target compounds, such as 11a, 11b and 11d, displayed good and broad spectrum antimicrobial activities with relative low MIC values against most of tested strains. These dinuclear complexes gave comparable or even better antimicrobial efficiencies than the reference drugs Fluconazole and Chloromycin. The result showed that the metal ions were the key factors to enhance the antimicrobial activities for mononuclear or dinuclear complexed in varying degrees. The interaction evaluation of compound 11b with bovine serum albumin (BSA) as an example was tested by fluorescence method. The thermodynamic parameters indicated that the hydrogen bonds and van der waals forces played the major roles in the strong association between dinuclear compound and BSA. The CCK-8 tests also confirmed the safeties of these dinuclear compounds in vitro.11a: the MIC50 of Candida albicans = 0.5 μg mL−1; 11b: the MIC50 of C. albicans = 1 μg mL−1; Fluconazole: the MIC50 of C. albicans = 0.5 μg mL−1. 11a: the MIC50 of Bacillus proteus = 0.5 μg mL−1; 11b: the MIC50 of B. proteus = 1 μg mL−1. Chloromycin: the MIC50 of B. proteus = 2 μg mL−1.