Development of new 2-piperidinium-4-styrylcoumarin derivatives with large Stokes shifts as potential fluorescent labels for biomolecules

A series of novel 2-piperidinium-4-styrylcoumarin derivatives, with large Stokes shifts and high fluorescence quantum yields, were synthesized using an efficient and low-cost synthetic strategy as potential fluorescent labels for biomolecules. Density functional theory and time-dependent density functional theory calculations were performed in order to rationalize the observed photophysical properties.

New 2-piperidinium-4-styrylcoumarin derivatives, with large Stokes shifts and high fluorescence quantum yields, as potential fluorescent labels for biomolecules.     

An expeditious synthesis of 6,7-dihydrodibenzo[b,j][4,7] phenanthroline derivatives as fluorescent materials

A rapid and efficient method has been developed for the synthesis of 13,14-dimethyl-6,7-dihydrodibenzo[b,j][4,7]phenanthroline derivatives (3a–d) through the Friedländer condensation of 2-aminoarylketone with 1,4-cyclohexanedione under solvent-free conditions using p-toluenesulphonic acid. The synthetic utility of compounds 3a, 3b, and 3c was demonstrated by synthesizing compounds 6a–kvia Suzuki coupling, 8 by Buchwald–Hartwig amination, and 9a–bvia NBS bromination. Significantly, the emission band corresponding to the π–π* electronic transition of compounds 3a, 6a, 6d, 6f, and 8 showed a redshift with increasing polarity of the solvents. Molar extinction coefficient (ε), Stoke''s shift (Δ ), and quantum yield (Φ_f) were calculated for all these compounds.

A rapid method has been developed for the synthesis of 13,14-dimethyl-6,7-dihydrodibenzo[b,j][4,7]phenanthroline derivatives (3a–d) through the Friedländer condensation of 2-aminoarylketone with 1,4-cyclohexanedione under neat conditions using p-TSA.     

Functionalized quinolizinium-based fluorescent reagents for modification of cysteine-containing peptides and proteins

A series of quinolizinium-based fluorescent reagents were prepared by visible light-mediated gold-catalyzed cis-difunctionalization between quinolinium diazonium salts and electron-deficient alkyne-linked phenylethynyl trimethylsilanes. The electron-deficient alkynyl group of the quinolizinium-based fluorescent reagents underwent nucleophilic addition reaction with the sulfhydryl group on cysteine-containing peptides and proteins. The quinolizinium-based fluorescent reagents were found to function as highly selective reagents for the modification of cysteine-containing peptides and proteins with good to excellent conversions (up to 99%). Moreover, the modified BCArg mutants bearing cationic quinolizinium compounds 1b, 1d, 1e and 1h exhibit comparable activity in enzymatic and cytotoxicity assays to the unmodified one.

New quinolizinium-based fluorescent reagents were made by visible light-mediated gold-catalyzed cis-difunctionalization of quinolinium diazonium salts and trimethylsilyl alkyne derivatives.     

Rhodamine-based cyclic hydrazide derivatives as fluorescent probes for selective and rapid detection of formaldehyde

We describe fluorescent probes to detect formaldehyde (FA) in aqueous solutions and cells. The probes rapidly respond to FA in aqueous solutions and have great selectivity toward FA over other biologically relevant analytes. The results of cell studies reveal that probe 1 can be utilized to monitor endogenous and exogenous FA in live cells.

We developed a fluorescent probe that is useful to monitor endogenous and exogenous formaldehyde in live cells.

Reactive carbonyl species (RCS) produced through metabolic processes are highly reactive and, thus, their overproduction causes damage to a variety of organisms.¹ Formaldehyde (FA), the simplest RCS, is a human toxin and carcinogen as a result of its ability to crosslink DNA and proteins.² FA is generated in cells by several metabolic events, including methanol oxidation, histone demethylation and N-methylamine deamination.³ During normal metabolic processes, the concentration of FA is maintained at physiological levels in the range from 100 μM in blood to 200–400 μM in brain,⁴ where it is involved in spatial memory formation and cognition.⁵ However, upregulation of FA-producing enzymes or exposure to exogenous FA (e.g., industrial pollutants, cigarette smoke, and natural products) can lead to abnormal elevation of FA levels up to as much as 800 μM.^4,5 Elevated levels of FA cause memory impairments, cancers, diabetes and neurodegenerative disorders.⁶ Owing to the physiological and pathological significance of FA, selective and sensitive tools to monitor this RCS in cells are in critical demand.Fluorescence imaging is a powerful method to detect intracellular analytes (e.g., ions, reactive species and biomolecules) owing to its advantageous features such as operational simplicity, sensitivity and non-invasive properties.⁷ Several fluorescent probes for detection of FA in cells, which are based on specific chemical reactions including 2-aza-Cope rearrangement, formimine reaction and aminal formation, have been devised thus far.⁸ However, most of these probes have drawbacks such as low selectivities over other aldehydes and/or slow fluorescence responses to FA.To develop FA-responsive fluorescent probes that do not suffer from the limitations described above, we designed rhodamine-based cyclic hydrazide derivatives 1 and 2 (Scheme 1), which should be weakly fluorescent owing to the absence of an appropriate fluorophore. We reasoned that the tethered amine groups in 1 and 2 would react with FA to form iminium ions A, which would then undergo intramolecular addition of the hydrazide NH to generate cyclic aminals B. We also envisaged that rapid opening of spirocyclic moiety in B would take place to generate highly fluorescent xanthenes C.⁹Open in a separate windowScheme 1The proposed mechanism of fluorescence sensing of formaldehyde by rhodamine cyclic hydrazide-based probes 1 and 2.On the basis of this strategy, the new FA-reactive fluorescent probes 1 and 2 were synthesized using reactions of rhodamine B acid chloride with the corresponding amine-appended hydrazines (Schemes S1–S3^†). All new compounds were characterized using standard spectroscopic methods. To assess the design strategy displayed in Scheme 1, we measured time-dependent changes in the intensities of fluorescence arising from the probes following treatment with FA at a physiologically relevant concentration (10 equiv., 100 μM) in PBS buffer (1% DMSO, pH 7.4).⁴ As shown in the spectra and plots (Fig. 1a and S1^†), the secondary amine tethered probe 1 underwent an immediate fluorescence response to FA and the emission intensity reached a maximum within 5 min. In the case of probe 2 containing a primary amine appendage, the fluorescence intensity promoted by treatment with FA reached a plateau after 2 min but a lesser extent than that from 1 (Fig. S2^†). The pseudo-first-order rate constants for the fluorescence-monitored reactions of 1 and 2 with FA were determined to be k = 1.8 × 10⁻² M⁻¹ s⁻¹ and 4.6 × 10⁻² M⁻¹ s⁻¹, respectively (Fig. S3^†).¹⁰ The FA-concentration dependencies of reactions of probes 1 and 2 in aqueous buffer were determined by measuring fluorescence intensities, 10 min after treatment of the probes with 10 equiv. FA. The results showed that 1 and 2 exhibit a respective 15- and 6.5-fold enhancement in fluorescence intensity after addition of 50 equiv. FA (Fig. 1b and S4^†).Open in a separate windowFig. 1(a) Time-dependent change of the fluorescence spectra of 1 (10 μM) promoted by addition of 10 equiv. FA in PBS buffer (1% DMSO, pH 7.4) at 37 °C (λ_ex = 520 nm). Inset is a plot corresponding to the time-dependent increase in fluorescence intensity of 1 following addition of FA (λ_ex/λ_em = 520/583 nm). (b) FA concentration-dependent changes of the fluorescence spectra of 1 (10 μM), 10 min after each addition of FA. Inset is a plot corresponding to the FA concentration-dependent increase in fluorescence intensity of 1 (10 μM). (c) Color and fluorescence (FI) images of probe 1 in the absence and presence of FA.The selectivity of fluorescence responses of the probes toward FA was then assessed by individually treating 1 and 2 (10 μM) with various biologically relevant analytes, including reactive carbonyl species (FA, acetaldehyde, benzaldehyde, 4-hydroxybenzaldehyde, ethyl pyruvate, ethyl glyoxalate, propionaldehyde, glucose), reactive oxygen species (H₂O₂, HOCl, NO˙, ¹O₂, O₂˙⁻, ˙OH) and cations (Cu²⁺, Fe²⁺, Fe³⁺, K⁺, Zn²⁺). The results showed that both probes respond to FA but not to the other analytes (Fig. 2 and S5^†). Taken together, the above findings indicate that probes 1 and 2 respond rapidly and selectively to FA in aqueous buffer.Open in a separate windowFig. 2Change of fluorescence intensity of 1 (10 μM) at 583 nm (λ_ex = 520 nm) promoted by addition of each of biologically relevant analytes (10 equiv.) in PBS buffer (1% DMSO, pH 7.4) at 37 °C. Numbering of the analytes in the graph is as follows: 1, acetaldehyde; 2, benzaldehyde; 3, 4-hydroxybenzaldehyde; 4, ethyl pyruvate; 5, ethyl glyoxalate; 6, propionaldehyde; 7, d-glucose (1 mM); 8, H₂O₂; 9, HOCl; 10, NO˙; 11, ¹O₂; 12, O₂˙⁻; 13, ˙OH; 14, Cu²⁺; 15, Fe²⁺; 16, Fe³⁺; 17, K⁺; 18, Zn²⁺; 19, FA.To shed light on the mechanistic basis for the responses of probes to FA, the product generated by reaction of 1 and FA was isolated (see ESI^† for the detailed procedure) and characterized by using spectroscopic methods. Analysis of the ¹H and ¹³C NMR spectra of the isolated product in CDCl₃ suggests that a 1,2,4-triazinane ring system exists, as judged from chemical shifts that correspond to bridging methylene protons (CH₂) and carbon (3.24 ppm (s, 2H) and 72.5 ppm, respectively) (Scheme 2). Also, the spectral analysis suggests that the isolated product contains a spirocyclic ring system because of the presence of a signal at 61.3 ppm in the ¹³C NMR spectrum, which is expected for a quaternary carbon in a spiro ring. Furthermore, analysis of UV-Vis absorption and fluorescence spectra revealed that the product in CH₂Cl₂ displays very weak absorbance at 560 nm as well as very weak fluorescence at 583 nm (Fig. S6^†). These observations led us to conclude that the product in CH₂Cl₂ has the spirocyclic structure represented by 3 (Scheme 2).Open in a separate windowScheme 2Solvent (nonpolar organic solvent versus aqueous buffer) dependence of the equilibrium between ring-closed (3) and open (4) forms of the product generated by reaction of 1 with FA.In contrast, the isolated product in aqueous buffer (1% DMSO, pH 7.4) had a strong absorbance at 560 nm and intense fluorescence at 583 nm (Fig. S7^†), spectral properties that are quite similar to those of the substance generated by treatment of 1 with FA in aqueous buffer. Collectively, the results suggest that while the product of the reaction of 1 with FA exists in the ring-closed form 3 in nonpolar organic solvents, in aqueous buffer it exists in the ring-opened xanthene containing form 4 (Scheme 2). As a consequence, it is reasonable to conclude that the reaction responsible for fluorescence generation when 1 is treated with FA in aqueous buffer involves formation of 4. In addition, extinction coefficients (ε₅₁₄), quantum yields and fluorescence outputs (quantum yield × ε₅₁₄) of 1, 2 and 3 were determined (Table S1^†). Furthermore, the limits of detection of 1 and 2 for FA were calculated to be 1.24 μM and 0.59 μM, respectively (Fig. S8^†).Next, the utility of 1 to image FA in live cells was evaluated. Because 1 displayed a larger increase in fluorescence intensity upon treatment with FA than does 2, 1 was utilized in the cell studies described below. To determine the optimal conditions for cell imaging, HeLa cells (human cervical cancer cells) were incubated with 10 μM 1 for various times and with various concentrations of 1 for 1 h. Analysis of confocal fluorescence microscopy images showed that cells exposed to 10 μM 1 for 0.5–1 h display the intense fluorescence signal (Fig. S9^†). In addition, based on the results of an MTT assay as well as the observation of an intact nucleus morphology, 1 had negligible cell death activity under these treatment conditions (Fig. S10^†).We also probed the FA concentration-dependence of the fluorescence response of 1. For this purpose, HeLa cells were first treated with 10 μM 1 and then incubated with concentrations of FA (0–1.0 mM) that are in a physiologically relevant concentration range (ca. 400 μM in normal cells and up to 700–800 μM in cancer tissues).^4,11 The results showed that fluorescence signals arising from 1 in cells increase gradually as the FA concentration increases (Fig. 3), indicating the ability of 1 to serve as a probe for FA in live cells.Open in a separate windowFig. 3Detection of FA in cells using probe 1. HeLa cells were incubated with 1 (10 μM) for 1 h followed by treatment with several concentrations of FA for 1 h. Cell images were obtained using confocal fluorescence microscopy (scale bar = 10 μm). The nucleus was stained with Hoechst 33342. The graph shows normalized fluorescence intensity (FI) in the treated cells (mean ± s.d., n = 3).To evaluate the detection of endogenous FA in cells, several cell lines, including HeLa, MRC-5 (human fibroblast cell line derived from normal lung tissue), HaCaT (human keratinocytes), HEK293T (human embryonic kidney cells) and MCF-7 cells (human breast cancer cells), were incubated with 1 for 1 h. Analysis of cell images revealed that whereas the treated HEK293T cells display the low fluorescence intensity,⁸ⁱ the other four cell lines exhibit similarly strong fluorescence (Fig. 4 and S11^†). The findings indicate that while HEK293T cells produce a low level of FA, the other four cells generate high levels of FA.Open in a separate windowFig. 4Detection of endogenous FA in cells using probe 1. MRC-5, HaCaT, HEK293T, HeLa and MCF-7 cells were incubated individually with 1 (10 μM) for 1 h. Cell images were obtained using confocal fluorescence microscopy (scale bar = 10 μm). The nucleus was stained with Hoechst 33342. The graph shows fluorescence intensities in the treated cells (mean ± s.d., n = 3).It is known that FA is generated in cells by the actions of several demethylases and oxidase enzymes.³ The enzyme lysine-specific demethylase 1 (LSD1) catalyzes the removal of one or two methyl groups from modified lysines to produce free lysine and FA.^3,12 Also, it is known that GSK-LSD1 serves as a potent inhibitor of LSD1.¹³ As a result, production of FA by LSD1 in cells was evaluated by incubating MCF-7 cells with 1 in the absence and presence of GSK-LSD1. The results revealed that the intensity of the fluorescence arising from probe 1 in MCF-7 cells is slightly attenuated when GSK-LSD1 is present (Fig. 5 and S12^†).^8b The findings suggest that LSD1-promoted generation of FA in cells does not occur at high levels in comparison to the amounts formed by several other metabolic events. Taken together, the findings demonstrate that the rhodamine-based probe 1 is capable of detecting endogenous and exogenous FA in live cells.Open in a separate windowFig. 5The effect of an inhibitor on LSD1-promoted generation of FA in cells. MCF-7 cells were incubated with 1 μM GSK-LSD1 for 20 h followed by incubation with 1 (10 μM) for 1 h. Cell images were obtained using confocal fluorescence microscopy (scale bar = 10 μm). The nucleus was stained with Hoechst 33342. The graph shows normalized fluorescence intensities in the treated cells (mean ± s.d., n = 3).In conclusion, we have developed novel rhodamine-based cyclic hydrazide derivatives as fluorescent probes for the detection of FA in both aqueous media and live cells. Upon addition of FA to the probes in aqueous buffer, a fluorescence enhancement occurs within a few minutes. In addition, the probes respond to FA but not to other biologically relevant species, indicating that they have a high selectivity toward FA. Furthermore, the results of cell studies demonstrate that probe 1 can be employed to image exogenous and endogenous FA in live cells. As a result, this probe should be useful in efforts aimed at gaining a more detailed understanding of FA-associated biological processes.     

A catalyst- and solvent-free protocol for the sustainable synthesis of fused 4H-pyran derivatives

An efficient and cost-effective method was developed for the synthesis of two kinds of fused 4H-pyran derivatives, namely, dihydropyrano[2,3-c]pyrazole 4 and pyrano[3,2-c]chromenone 6. The reactions of 3-methyl-1-phenyl-5-pyrazolone/4-hydroxycoumarin with aromatic aldehydes and (E)-N-methyl-1-(methylthio)-2-nitroethenamine (NMSM), involving the Knoevenagel, Michael-addition, O-cyclization and elimination reactions under thermal heating, afforded the desired products. The synthesized compounds were characterized by standard spectroscopic techniques. Further, the structures of pyrazole-fused 4H-pyran 4a and coumarin-fused 4H-pyran 6b were confirmed by single-crystal XRD analysis. The short reaction time, good-to-excellent yields, elimination of the use of expensive, metallic and toxic catalysts or hazardous organic solvents and high atom-economy are some noteworthy features of this protocol.

A practical and greener method for the synthesis of highly functionalized pyrazole and coumarin fused 4H-pyran derivatives by exploring NMSM under neat conditions at 110 °C is described.     

Catalysis as a key technology for the environmentally benign synthesis of amines and amino acids.

The rhodium-catalyzed amination of aromatic olefins and the palladium-catalyzed amidocarbonylation of aldehydes are presented as new atom-efficient methods to yield biologically interesting amines and N-acyl amino acids.     

Phase-trafficking reagents and phase-switching strategies for parallel synthesis.

Strategies for the parallel synthesis of small molecule arrays are reviewed with an emphasis on those approaches that integrate the sciences of organic synthesis and product purification. The use of phase-trafficking reagents (PTRs) and phase-switching strategies are highlighted, which allow the rapid, parallel synthesis of small molecule arrays with built-in purification determinants.     

Lectins as reagents for the differentiation of serum enzymes. Lectins as reagents, I. (author's transl)

Lectins from Canavalia ensiformis, Phaseolus vulgaris, and Triticum vulgare react with arylamidase, alkaline phosphatase, gamma-glutamyltransferase, and cholinesterase of human sera by formation of enzymatically active, mostly insoluble complexes. Arylamidase, alkaline phosphatase, and cholinesterase react more intensely in sera of healthy people than in sera of patients with liver and neoplastic diseases. Arylesterase is bound to a distinct degree only by concanavalin A. The enzymes mentioned above also react slightly with the following lectins in order of decreasing intensity: Ricinus communis, Arachis hypogaea, Helix pomatia, Glycine max, Dolichos biflorus, and Ulex europaeus. Though multiple forms containing less sialic acid are favourably bound, preincubation with neuraminidase does not improve the reaction except with soybean lectin. Since higher concentrations of lectins react also with fast moving fractions of high sialic acid content, no steric hindrance of the binding between lectins and sialoenzymes is supposed, as concluded from determination of the total enzyme activity.     

国产和进口荧光定量PCR试剂检测HBV-DNA的比对分析

目的分析国产和进口实时荧光定量聚合酶链反应(PCR)试剂检测乙型肝炎病毒(HBV)-DNA的相关性,探讨国产和进口试剂在临床应用中的差异。方法使用国产和进口试剂平行检测262例乙型肝炎(乙肝)患者血浆当中的HBV-DNA水平,国产试剂采用手工提取标本,罗氏LightCycler480Ⅱ(LC480Ⅱ)进行核酸扩增;进口试剂则采用罗氏COBAS AmpliPrep(CAP)和COBAS Taqman48(CTM)进行标本提取和扩增;对HBV-DNA病毒载量数据进行对数转换(log10),并将两组数据进行相关分析。结果国产和进口试剂检测结果,经线性拟合,R2=0.814 3。HBV-DNA浓度在10~103 IU/mL的标本,R2=0.300 6;浓度在104~105 IU/mL的标本,R2=0.411 8;浓度在106~108 IU/mL的标本,R2=0.801 7。进口试剂阳性检出率为75.57%(198/262),明显高于国产试剂阳性检出率[65.65%(172/262)]。结论国产试剂和进口试剂相比,相关性良好。HBV-DNA浓度在106~108IU/mL时,相关性最高;浓度在104~105 IU/mL时,相关性一般;浓度在10~103 IU/mL时相关性较差,国产试剂与进口试剂有明显差异,灵敏度有待进一步提高。     

One-step synthesis of fluorescent graphene quantum dots as an effective fluorescence probe for vanillin detection

This study proposes an easy bottom-up method for the synthesis of photoluminescent (PL) graphene quantum dots (GQDs) using citric acid as the carbon source. The obtained GQDs were characterized by high-resolution transmission electron microscopy (HRTEM), UV-vis absorption spectroscopy, fluorescence spectroscopy, and Fourier transform infrared spectroscopy (FT-IR). The synthesised GQDs have an average diameter of 4.76 ± 0.96 nm, with a lattice spacing of 0.24 nm. The GQDs exhibit excitation-independent PL emission. The surface of the GQDs has a variety of functional groups (hydroxyl, carboxyl, and ether groups etc.) to enhance its stability and water solubility. In this study, a fluorescent “on–off” sensor is developed for the selective detection of vanillin in chocolates using GQDs as a fluorescent probe. Under optimal conditions, fluorescence intensity of the GQDs has a good linear relationship with the vanillin concentration (0.0–2.1 × 10⁻⁵ mol L⁻¹), with a limit of detection of 2.5 × 10⁻⁸ mol L⁻¹. For detection in real samples, the percent recovery of vanillin and the relative standard deviation were 88.0–108.9% and 0.90–5.4%, respectively. Thus, this GQDs-based method has good accuracy and precision and can be used for vanillin detection in practical applications.

This study proposes an easy bottom-up method for the synthesis of photoluminescent (PL) graphene quantum dots (GQDs) using citric acid as the carbon source.     

Evaluating the accuracy and diagnostic value of CFW and a new fluorescent reagents,fluorescent brightener 85, for the diagnosis of vulvovaginal candidiasis

BackgroundVulvovaginal candidiasis (VVC) is a common vaginitis in females. The commonly used diagnostic method, 10% potassium hydroxide (KOH) smear microscopy, makes it not very easy to recognize fungi.MethodsVaginal secretions were collected from clinically suspected VVC patients and divided into four groups and examined using KOH, CFW (Calcofluor White), FB 85(fluorescent brightener 85), and culture. The data were statistically analyzed.ResultsIn total, 110 patients with suspected VVC were recruited. The positive rates of KOH, CFW, FB 85, and the culture method were 68.2%, 64.5%, 61.8%, and 77%, respectively. According to the McNemar test, there was no statistically significant difference between the KOH, CFW, and the FB 85 methods (p > 0.05). However, CFW had a shorter diagnosis time than the KOH method and had a statistically significant difference (p < 0.001). Moreover, CFW has the highest sensitivity, specificity, and accuracy. In morphological recognition, it was easier to recognize fungal structures with CFW and FB 85 than with the KOH.ConclusionsThe fluorescent method is a good method for the diagnosis of VVC. And the fungi can be found more quickly. Similar to CFW, FB 85 is also a potential good fluorescent reagent for the diagnosis of VVC and has potential value for application in clinical fungal infection diseases.     

One-pot synthesis of 2-amino-4H-chromene derivatives by MNPs@Cu as an effective and reusable magnetic nanocatalyst

In this research, MNPs@Cu as an effective and recyclable nanocatalyst was prepared and characterized using different methods including Fourier transform infrared spectroscopy (FT-IR), thermogravimetric analysis (TGA), vibrating sample magnetometry (VSM), scanning electron microscopy (SEM), energy dispersive X-ray spectroscopy (EDX), and X-ray diffraction (XRD). After the characterization of this new nanocatalyst, it was efficiently used for the promotion of the one-pot synthesis of 2-amino-4H-chromene derivatives via one-pot three-component reaction of the enolizable compound, malononitrile, and arylaldehydes under solvent-free conditions at 90 °C. The procedure gave the desired products in high-to-excellent yields in short reaction times. Also this catalyst, because of its magnetic nature, can be simply restored by a permanent magnetic field and comfortably reused several times without any significant loss of its catalytic activity.

MNPs@Cu as an effective, recyclable nanocatalyst was prepared and characterized using Fourier transform infrared spectroscopy, thermogravimetric analysis vibrating sample magnetometry, scanning electron microscopy, energy dispersive X-ray spectroscopy and X-ray diffraction.     

DABCO bond cleavage for the synthesis of piperazine derivatives

The applications of DABCO (1,4-diazabicyclo[2.2.2]octane) in the synthesis of piperazine derivatives including biologically active compounds via C–N bond cleavage are investigated in this review. Different reagents such as alkyl halides, aryl(heteroary) halides, carboxylic acids, diaryliodonium salts, tosyl halides, activated alkynes, benzynes etc. were applied for the preparation of the corresponding quaternary ammonium salts of DABCO, which are very good electrophiles for various nucleophiles such as phenols, thiophenols, thiols, alcohols, aliphatic and aromatic amines, sulfinates, phthalimide, indoles, NaN₃, triazole and terazoles, NaCN, enols and enolates, halides, carboxylic acid salts etc. Besides preactivated DABCO salts, the in situ activation of DABCO in multicomponent reactions is also an efficient tactic in synthetic organic chemistry for the diversity oriented synthesis of drug-like piperazine derivatives.

The applications of DABCO (1,4-diazabicyclo[2.2.2]octane) in the synthesis of piperazine derivatives including biologically active compounds via C–N bond cleavage are investigated in this review.     

Novel biotinylated acridinium derivatives: new reagents for fluorescence immunoassays and proteomics

BACKGROUND: The favorable properties of acridinium derivatives over conventional fluorescent probes have attracted considerable interest. These conjugates have found wide utility in tests developed for medical diagnosis providing at least comparable sensitivity to radioimmunoassay (RIA) and enzyme immunoassay (EIA) procedures. METHODS: In this paper we describe the synthesis, luminescent properties and immunoassay applications of two novel biotinylated acridinium derivatives, 9-(2-biotinyl-oxyethyl)-carboxylate-10-methyl-acridinium triflate, BOCMAT and 9-(2-biotinyl-amidoethyl)-carboxylate-10-methyl-acridinium triflate, BACMAT. RESULTS: The chemiluminescence efficiency of the novel reagents is high in polar aprotic solvents and attains detection limits down to 7.28 x 10(-8) M, while the fluorescence efficiency has its maximum in aqueous solutions with detection limits down to 1.94 x 10(-10) M. The above novel compounds were applied in the fluorimetric determination of solid phase-immobilized biotinylated mouse IgG and the detection limit was found to be approximately 1 microg/assay ( approximately 7 pmol/assay). CONCLUSIONS: The new streptavidin-based detection reagents were synthesized can be used for the development of highly sensitive solid-phase fluorescence-based immunoassays and may find important applications in proteomics.     

Facile synthesis of carbon nitride quantum dots as a highly selective and sensitive fluorescent sensor for the tetracycline detection

Enhanced blue fluorescent carbon nitride quantum dots (g-C₃N₄QDs) were synthesized by a simple solvothermal “tailoring” process from bulk g-C₃N₄ and analyzed by various characterization methods. The as-obtained g-C₃N₄QDs were successfully applied in the determination of tetracycline (TC) with a good linear relationship in the range of 0.23–202.70 μM. The proposed fluorescent sensor shows excellent stability, good repeatability, high selectivity and outstanding sensitivity to TC with a low detection limit of 0.19 μM. The fluorescence quenching mechanism of g-C₃N₄QDs with TC was mainly governed by static quenching and the inner filter effect. The method was successfully applied to monitor TC in tap water and milk powder samples.

The g-C₃N₄QDs were synthesized by a simple solvothermal “tailoring” process from bulk g-C₃N₄ which have a “strong quenching” behaviour in the presence of TC. The proposed fluorescent sensor has been successfully applied to detect TC in actual samples.     

A facile synthesis of 1,3,6,8-pyrenesulfonic acid tetrasodium salt as a hydrosoluble fluorescent ink for anti-counterfeiting applications

In this work, 1,3,6,8-pyrenesulfonic acid sodium salt (PTSA) was successfully synthesized via a one-step sulfonating reaction. This method is more convenient, effective and eco-friendly than the traditional one. The as-prepared PTSA exhibits pure blue fluorescence under UV light. Due to its excellent fluorescent properties and water solubility, PTSA was used to prepare water-soluble invisible inks based on hydroxyethyl cellulose (HEC) aqueous solution. Notably, the resulting inks possessed acceptable stability after being stored for 30 days. Besides, the red/green/blue fluorescent inks were obtained by adding extra pigments, all of which exhibited excellent rheology and thixotropy properties. Subsequently, various patterns, including a QR code, the logo of Wuhan University, Chinese characters and so on, were printed on non-background paper through ink-jet and screen printing, and the as-prepared materials exhibited good water solubility and outstanding fluorescence performances, indicating that the fluorescent PTSA material is a promising candidate for anti-counterfeiting applications.

In this work, 1,3,6,8-pyrenesulfonic acid sodium salt (PTSA) was successfully synthesized via a one-step sulfonating reaction and exhibited the potential in anti-counterfeiting.     

3-Hydroxyflavone derivatives: promising scaffolds for fluorescent imaging in cells

As a typical class of excited-state intramolecular proton transfer (ESIPT) molecules, 3-hydroxyflavone derivatives (3HF, also known as flavonols) have received much attention recently. Thereinto, the role of hydrophobic microenvironment is significant importance in promoting the process and effects of ESIPT, which can be regulated by the solvents, the existence of metal ions and proteins rich with α-helix structures or the advanced DNA structures. Considering that plenty of biological macromolecules offer cellular hydrophobic microenvironment, enhancing the ESIPT effects and resulting in dual emission, 3HF could be a promising scaffold for the development of fluorescent imaging in cells. Furthermore, as the widespread occurance of compounds with biological activity in plants, 3HF derivatives are much more secure to be cellular diagnosis and treatment integrated fluorescent probes. In this review, multiple regulatory strategies for the fluorescence emission of 3HF derivatives have been collectively and comprehensively analyzed, including the solvent effects, metal chelation, interaction with proteins or DNAs, which would be beneficial for ESIPT-promoting or ESIPT-blocking processes and then enhance or control the fluorescence emission of 3HF effectively. We expect that this review would provide a new perspective to develop novel 3HF-based fluorescent sensors for imaging in cells and plants.

Considering that biological macromolecules offer hydrophobic microenvironment, 3HF is a promising scaffold for the development of fluorescent imaging in cells.     

Zr@IL-Fe3O4 MNPs as an efficient and green heterogeneous magnetic nanocatalyst for the one-pot three-component synthesis of highly substituted pyran derivatives under solvent-free conditions

The present study was conducted to synthesize Zr@IL-Fe₃O₄ MNPs as a new magnetically recoverable heterogeneous catalyst, which was then characterized by Fourier transform infrared (FT-IR) spectroscopy, energy dispersive X-ray spectroscopy (EDX), vibrating sample magnetometry (VSM), X-ray diffraction (XRD), thermogravimetric analysis (TGA), scanning electron microscopy (SEM), and transmission electron microscopy (TEM) techniques. The catalytic behavior of the Zr@IL-Fe₃O₄ MNPs was efficiently used for the synthesis of highly substituted pyran derivatives via a one-pot three-component condensation of 4-hydroxycoumarin/dimedone, malononitrile, and arylaldehydes under solvent-free conditions. This new methodology demonstrated some important features, including short reaction times, excellent yields, lower loading of the catalyst, easy work-up, and recyclability of the catalyst for a minimum of six times without any noticeable decrease in catalytic activity.

Synthesis of highly substituted pyran derivatives using Zr@IL-Fe₃O₄ MNPs.