Simultaneous detection and removal of 2,4,6-trinitrophenyl phenol and dichromate by metal-organic framework.

2,4,6-trinitrophenyl phenol (TNP) and dichromate (Cr2O72-) have serious toxicological effects on environment. Therefore, it is very important to detect and remove TNP and Cr2O72- in environmental matrix. In this work, a dual-functional UiO type metal-organic framework (Zr-Sti) was synthesized for simultaneous detection and removal of those pollutants in aqueous solution. As for detection, Zr-Sti exhibited sensitive and selective fluorescence response to TNP and Cr2O72- with detection limit below µM level, and possible mechanism behind was proposed and partially supported by experiment data. In addition, adsorption capacity of the prepared Zr-Sti for TNP and Cr2O72- was further investigated to evaluate its performance in pollutant removal from aqueous solution, and the mechanism behinds the obtained high removal efficiency was proposed. These results together with the satisfied recovery for simultaneous detection of TNP and Cr2O72- in real sample, indicate the potential of the prepared Zr-Sti material in the field of environment monitoring and remediation.

Dual-responsive ratiometric fluorescent sensor for tetracyclines detection based on europium-decorated copper nanoclusters.

Development of accurate and efficient TCs residue analysis methods is of great significance for the protection of environment, food safety and public health. Herein, a dual-responsive ratiometric fluorescence sensor being capable of simple and sensitive detection of tetracycline (TC) was presented, which was constructed by immobilizing europium ions (Eu3+) onto the mercaptopropionic acid stabilized copper nanoclusters (MPA-Cu NCs). In the presence of TC, the red fluorescence of Eu3+ was enhanced through antenna effect (AE), while the green fluorescence of MPA-Cu NCs was quenched through internal filter effect (IFE), leading to an obvious fluorescence color evolution from green to red for the probe solution. In addition to successful design of a smartphone-assisted colorimetric analysis platform for portable detection, a logic gate device capable of intelligently monitoring TC concentration is also designed.

Highly selective and sensitive determination of ceftriaxone sodium using nitrogen-rich carbon dots based on ratiometric fluorescence.

Selective and sensitive determination of ceftriaxone sodium (CTR) trace residues is of great importance for food safety and environmental protection. Herein, a determination method based on ratiometric fluorescence and colorimetric method with nitrogen-rich carbon dots as fluorophore is reported. The functional surfaces of indole-derived carbon dots (I-CDs) containing nitrogen and carbon groups can be selectively bound to CTR by electrostatic forces, leading to a hindered conjugation system and deprotonation of the amine on the pyrrole ring, resulting in a distinct variety in fluorescence and absorption wavelength and intensity. With the addition of CTR, the fluorescence at 577 nm can be selectively quenched, accompanied by a new emission peak appeared at 507 nm. The limits of detection (LODs) were estimated to be 19.7 nM and 78.0 nM based on the ratiometric fluorescence method and colorimetric method, respectively. Finally, the in situ visual quantitative determination of CTR using this nanosensor was achieved by combining with the color recognizer of a smartphone, and the method was further validated by spike and recovery test in real water samples including milk, seawater, and tap water.

Conformational transition-induced simultaneous fluorescence enhancement of oxytetracycline and rhodamine B under a single excitation wavelength.

Since the abuse of antibiotic oxytetracycline (OTC) poses a serious threat to the environment and human health, it is of great importance to develop sensitive fluorescent probes for its rapid and in situ detection. Herein, a dual fluorescence response probe based on an aluminum-incorporated metal-organic framework (MOF) was presented for OTC assay. Unlike internal references that demonstrate an independent and stable fluorescence signal intensity in traditional dual-emissive probes, the fluorescence of rhodamine B immobilized in a prepared probe was gradually enhanced at a 585 nm emission wavelength with increasing concentrations of OTC under 405 nm excitation, while OTC also experienced an obvious fluorescence enhancement at a 521 nm emission wavelength due to a molecular conformation transition from the twisted to the extended state, realizing a molecular conformational transition-induced dual fluorescence enhancement for OTC detection under a single excitation wavelength. In addition to the mechanism exploration and double linear range for OTC quantification with nM level detection limits in solution, a paper-based portable test strip was successfully fabricated by loading the probe on glass fiber filter paper with an obvious fluorescence color change from orange to yellow upon increasing the addition of OTC. We expect that the proposed probe in this work would provide an example for the design of organic fluorophore-based sensors exhibiting multiple fluorescence responses under a single excitation.

Excitation-dependent ratiometric fluorescence response to mercury ion based on single hexagonal boron nitride quantum dots.

Since a vast majority of mercury ion (Hg2+)-responsive fluorescence probes suffer from significant false positive interference in practical applications originating from their fluorescence quenching mechanism, it is still a challenge to develop a fluorescence enhancement sensor for its assay. In this work, single hexagonal boron nitride quantum dots (BNQDs)-based probe was presented for Hg2+ assay in a fluorescence enhancement-based ratiometric manner. When Hg2+ was present, the BNQDs exhibited a new fluorescence emission peak located at 560 nm under 280 nm excitation, while the original blue fluorescence of the probe at 461 nm was quenched, realizing a ratiometric fluorescence response to Hg2+. Furthermore, it is found that fluorescence enhancement at 560 nm was dramatically suppressed under 365 nm excitation, the mechanism behind this phenomenon has been explored by experiments and relevant theories. In addition to high selectivity and detection sensitivity with LOD of 0.7 nM, the prepared probe successfully demonstrated its accuracy in Hg2+ detection in environmental water samples. Moreover, the probe could be adopted for paper sensor design, and an accurate and reliable cell phone-based portable platform was demonstrated for Hg2+ assay with LOD of 1.9 nM, suggesting its potential in point-of-care detection application.

Paper-based device for the selective determination of doxycycline antibiotic based on the turn-on fluorescence of bovine serum albumin-coated copper nanoclusters.

An enhanced ratiometric fluorescence sensor was built for on-site visual detection of doxycycline (DOX) through the interaction with bovine serum albumin on the surface of red emissive copper nanoclusters. Upon the addition of weakly fluorescent DOX, the red fluorescence from copper nanoclusters gradually decreased through the inner-filter effect (IFE), while a green fluorescence appears and significantly increases, forming an interesting fluorescent isosbestic point, which was assigned to DOX due to sensitization effect of bovine serum albumin. On the basis of this ratiometric fluorescence, the system possessed good limit of detection (LOD) of 45 nM and excellent selectivity for DOX over other tetracyclines. Based on these findings, a paper-based sensor has been fabricated for distinct visual detection of trace DOX and combined with smartphone color recognizer for quantitative detection of DOX (LOD = 83 nM). This method shows broad application prospects in environmental monitoring and food safety.

Methyl position affect the fluorescence performance of HBT derivatives for the detection of hypochlorite under alkaline condition.

Five fluorescent derivatives of hydroxyphenyl-benzothiazole (HBT) with different methyl positions at the hydroxyphenyl group were synthesized with good yield. Their reactivity and fluorescent response to hypochlorite were carefully studied. It was found that the HBT derivatives with meta-methyl (3-HBT or 5-HBT) showed the highest reactivity to hypochlorite under basic conditions, accompanied by the most efficient fluorescence quenching, whereas HBT derivatives with ortho or para methyl exhibited the least reactivity to hypochlorite. The LUMO and HOMO of 3-HBT were further verified to explain the fluorescence behavior by density functional theory (DFT) calculation. The excellent selectivity of 3-HBT toward hypochlorite against other reactive oxygen species (ROS) was also evaluated under the same conditions. The compounds emit bright green fluorescence in a solid-state, which is convenient for designing sensing devices for hypochlorite in water samples. Thus, the HBT derivatives with meta methyl (3-HBT) were successfully applied to fabricate paper sensors for the quantification of hypochlorite in tap water. Hence, the fluorescent 3-HBT exhibits great promise as a selective and sensitive hypochlorite probe in chemical and biological applications.

Fluorescent probe visualization for selective detection of cuprous ion.

Cuprous ion is an essential element for human life activities. However, excessive cuprous can cause dysfunction of the human body system. To help explain this evolving biology, we report a fluorescent probe for detecting unstable Cu(I). Cu(I) undergoes a metal complexation reaction with the sulfur element in the probe, resulting in a photoelectron transfer (PET) effect. The probe fluorescence is greatly suppressed, and rapid and selective visual detection of Cu(I) in the inorganic environment is realized. There is also a good linear relationship between the probe fluorescence intensity and the Cu(I) concentration (R2 = 0.992), which can realize the quantitative detection of Cu(I). When the probe concentration is 0.1 µM, the detection limit is 15 nM, and the detection limit of the visual method is as low as 0.1 µM. This work provides a valuable starting point for real-time monitoring of the Cu(I) concentration in a human anaerobic environment based on active probes.

Green-emitting carbon quantum dots as a dual-mode fluorescent and colorimetric sensor for hypochlorite.

In this work, green-emitting carbon quantum dots were successfully prepared through a facile one-step solid-state reaction method. The obtained green-emitting carbon dots (G-CDs) showed good fluorescence stability in NaCl aqueous solution and different pH values. Moreover, the G-CDs showed high sensitivity and selectivity for detecting hypochlorite by both fluorometry and colorimetry. Under the optimized condition, a highly sensitive detection of hypochlorite was established in the range of 0.2-100 µM and 10-150 µM for fluorescent and colorimetric methods, respectively. The corresponding limits of detection (LOD) were 0.0781 µM and 1.82 µM, respectively. Therefore, the G-CDs were successfully applied to determinate hypochlorite in actual water samples. In addition, a paper-based sensor loading with the G-CDs was also developed for rapid visual detection of hypochlorite. The results suggested that the G-CDs could be a promising candidate to detect hypochlorite.

Surface enhanced FRET for sensitive and selective detection of doxycycline using organosilicon nanodots as donors.

In order to achieve on-site fluorescent detection of antibiotic doxycycline (DOC) residue, a new kind of fluorescent organosilicon nanodots (OSiNDs) was successfully constructed by a one-pot strategy and used as a novel ratiometric fluorescent probe. This method could enhance the fluorescence of DOC by conformational fixation on the surface of OSiNDs, and subsequently induced fluorescence resonance energy transfer (FRET). Control experimental results showed that phenylamine functional groups on the as-prepared OSiNDs possessed favorable interactions with DOC by hydrogen bond/π-π stacking, leading to both conformational change of DOC molecules and fluorescence resonance energy transfer process from OSiNDs to DOC. This method was then adapted and optimized for visual sensitive and selective detection of DOC based on ratiometric fluorescence signal, displaying a good linear range for DOC in the range of 1-35 µM with an excellent limit detection of ∼80 nM. Other tetracycline derivatives (TCs) and possible interferences have little influence on the determination of DOC using the method. The spike and recovery test of DOC in real water samples demonstrated the feasibility of the OSiNDs for DOC assay in practical samples and a test paper was fabricated with OSiNDs loading, achieving easy and visual detection of DOC by naked eyes.

On-site detection of As(III) based on silver nanoparticles aggregation mediated by phosphates using surface-enhanced Raman scattering (SERS).

A portable and simple method was developed for on-site selective determination of As(III) based on the SERS signal of As(III)-O vibration. The method relies on the synergistic effect of nanoparticles aggregation and analyte adsorption. Experimental results demonstrated that phosphate replaced the ligands of HH@Ag NPs, which in turn facilitated the adsorption of As(III) on the surface of HH@Ag NPs. The phosphate was introduced as an agglomerating agent to improve the detection ability of the method for As(III). The method shows good selectivity and linear relationship between 5 × 10-8 and 0.8 × 10-6 M, with the detection limit of 1.8 × 10-9 M. The method was applied to actual water samples and successfully detected As(III), indicating that the method could have application potential in actual detection scenarios.

Novel Mcl-1/Bcl-2 dual inhibitors created by the structure-based hybridization of drug-divided building blocks and a fragment deconstructed from a known two-face BH3 mimetic.

We have previously reported a small-molecule two-face Bim BH3 mimetic, 2,3-dihydroxy-6-(4-isopropylphenylthio)anthracene-9,10-dione (1). Herein, we linked a polyphenol fragment, which was deconstructed from compound 1, with a drug-derived building block gained from computer-aided molecular design. 2-Phenyl-1H-benzo[d]imidazole as a new scaffold for two-face Bim mimetics was developed; based on this, a series of Mcl-1/Bcl-2 dual inhibitors were obtained. The most potent compound 6d binds to Mcl-1 and Bcl-2 with K(i) values of 127 and 607 nM, respectively, and effectively induces apoptosis in a dose-dependent, mechanism-based manner in multiple cancer cell lines.

Design, synthesis and structure-activity relationship studies of morpholino-1H-phenalene derivatives that antagonize Mcl-1/Bcl-2.

We report herein characteristic studies of Mcl-1 and Bcl-2 dual inhibitors. It was found that a protruding carbonyl group forming hydrogen bond with R263 plays a predominant role compared with the hydrophobic group that occupies the p2 pocket. A series of dual inhibitors representing different parts of the morpholino-1H-phenalene were designed, synthesized and evaluated.

Two-face, two-turn α-helix mimetics based on a cross-acridine scaffold: analogues of the Bim BH3 domain.

The design of a cross-acridine scaffold mimicking the i, i+3, i+5, and i+7 residues distributed over a two-face, two-turn α-helix is described. Docking studies and 2D (1)H, (15)N HSQC NMR spectroscopy provide compelling evidence that compound 3 d accurately reproduces the arrangement of four hotspots in the Bim BH3 peptide to permit binding to the Mcl-1 and Bcl-2 proteins (Ki 0.079 and 0.056 µM, respectively). Furthermore, the hotspot mutation could also be mimicked by individual or multiple deletions of side chains on the scaffold.

Design, synthesis and structure­activity relationship studies of morpholino-1H-phenalene derivatives that antagonize Mcl-1/Bcl-2.

We report herein characteristic studies of Mcl-1 and Bcl-2 dual inhibitors. It was found that a protruding carbonyl group forming hydrogen bond with R263 plays a predominant role compared with the hydrophobic group that occupies the p2 pocket. A series of dual inhibitors representing different parts of the morpholino-1H-phenalene were designed, synthesized and evaluated.

Study of binding thermodynamics in the optimization of BH3 mimetics.

The use of small molecule B-cell lymphoma 2 homology domain 3 mimetics to neutralize the B-cell lymphoma 2 protein is an attractive strategy for cancer treatment due to its ability to cause targeted cell apoptosis. We have previously reported the design and optimization of a series of B-cell lymphoma 2 homology domain 3-mimetics, called compounds 1-6. In this study, we evaluated the optimization of B-cell lymphoma 2 homology domain 3-mimetics from a thermodynamic perspective. Understanding the thermodynamic parameters of B-cell lymphoma 2 homology domain 3-mimetics plays a critical role in the development of B-cell lymphoma 2 small-molecule inhibitors. The thermodynamic parameters for the interactions of these compounds with the myeloid cell leukemia sequence 1 protein were obtained using isothermal titration calorimetry. Owing to compounds 1-6 overcoming enthalpy-entropy compensation, the affinities of them improved gradually. Toward binding to the myeloid cell leukemia sequence 1 protein, compound 6 was deemed optimal with an obtained Kd value of 238 nm, which is a 10(4) -fold improvement compared with 1. Analysis of the enthalpy and -TΔS efficiencies showed that ligand efficiencies with respect to molecular size are correlated with the enthalpic efficiencies. Notably, an enthalpy gain of 4.65 kcal/mol identified that an additional hydrogen bond is formed by 2 with myeloid cell leukemia sequence 1 compared with compound 1. For the first time, hydrogen bonding between a small-molecule inhibitor of B-cell lymphoma 2 was demonstrated experimentally.

3-Thiomorpholin-8-oxo-8H-acenaphtho [1,2-b] pyrrole-9-carbonitrile (S1) derivatives as pan-Bcl-2-inhibitors of Bcl-2, Bcl-xL and Mcl-1.

Based on the binding mode of our previously discovered dual inhibitor of Bcl-2 and Mcl-1, 3-thiomorpholin-8-oxo-8H-acenaphtho[1,2-b]pyrrole-9-carbonitrile (3, S1), a library of 9-substituted 3 derivatives was synthesized to further probe the p4 pocket of the two targets. By NMR, structure-activity relationship study, and site-directed mutation, compound 6d (3-(4-aminophenylthio)-8-oxo-8H-acenaphtho[1,2-b]pyrrole-9-3-phenyl)propylamine) was identified to span p2-p4 pockets of Mcl-1, Bcl-2 and Bcl-x(L), and then exhibited 9- to 35-fold better affinity to the three targets than 3 (IC(50)=10, 20 and 18 nM, respectively), which led to greater activity in induction of apoptosis in multiple cancer cell lines. Different contribution of p4 pocket to binding Bcl-2 and Mcl-1 was also investigated by plotting the potency and the HAC of the derivatives.