Surface-enhanced Raman scattering (SERS) by use of noble metal nanoparticles has become a powerful tool to determine a low-concentration target by unique spectral fingerprints, but it is still limited to the Raman-inactive and nonresonant biomolecules such as amine acids, proteins, and hormones. Here, we report an Ehrlich reaction based derivative strategy in combination with gold nanoparticles (Au NPs) hotspots for the selective detection of indole-like plant hormones by SERS spectroscopy. Ehrlich reaction of p-(dimethylamino)benzaldehyde (PDAB) with the indole ring chemically transformed plant hormone indole-3-butyric acid (IBA) into a Raman-active and resonant derivative with an extended π-conjugated system in the form of a cation, which produced a new absorption band at 626 nm. On the other hand, cationic IBA–PDAB highly evoked the aggregation of Au NPs with negative citrate ligands to form the effective Raman hotspots and gave rise to the new absorption ranging from 600 to 800 nm. Significantly, the spectral overlap among IBA–PDAB, aggregated Au NPs, and the exciting laser initiated the multiple optical resonances to generate the ultrahigh Raman scattering with a sensitive limit of 2.0 nM IBA. The IBA in the whole sprouts and various parts of pea, mungbean, soybean, and black bean has been identified and quantified. The reported method opens a novel avenue for the SERS detection of Raman-inactive analyte by a proper derivation.

An investigation of the potential neuroprotective natural product constituents of the rhizomes of Typhonium giganteum led to the isolation of two new cerebrosides, typhonosides E (1) and F (2), along with 11 known analogues (3–13). The structures of compounds 1 and 2 were elucidated by spectroscopic data interpretation. The activity of these compounds against glutamate-induced cell apoptosis was investigated in PC12 cells. All compounds exhibited such activity, which was related to the length of the fatty acyl chain. Among them, longan cerebroside II (11), with the longest fatty acyl chain, showed the most potent protective effect in PC12 cells from glutamate injury, with an EC50 value of 2.5 μM. Moreover, at the molecular level, longan cerebroside II (11) downregulated the expression of caspase-9, caspase-3, and Bax, upregulated the expression of Bcl-2, and decreased the level of cytosolic cytochrome c in a concentration-dependent manner.

•Iminodiacetic acid as a ligand was grafted on the vast surface of mesopores.•Doxorubicin was loaded at surface of PEGylated mesoporous silica nanoparticles via coordinate binding.•Enhanced drug loading, pH-responsive release and prolonged drug circulation time were achieved.To achieve drug targeting and on-demand releasing, surface functionalization plays a critical role in fabricating potential mesoporous silica nanoparticles (MSNs) toward tumor chemotherapy. Here, we prepared a size-controllable ligand-functionalized MSNs delivery system via coordinate bonding, which can release doxorubicin (DOX) in response to pH and prolong the circulation time of drug in vivo. After modifying the external surface of MSNs with polyethylene glycol (PEG), iminodiacetic acid (IDA) as a ligand was mainly grafted on the surface of mesopores to chelate cupric iron and DOX in sequence via coordinate bonds. The modified MSNs exhibited a uniform size of about 72 nm and could be stably dispersed in saline. After DOX loading, the drug loading content and encapsulation efficiency were calculated to be 9.3 ± 0.1% and 92.8 ± 0.6%, respectively. Moreover, the resultant MSNs showed a pH-responsive release property, which could avoid the premature leakage of drug in circulation and achieve on-demand release within the tumor cells. Additionally, the pharmacokinetic study in healthy rats demonstrated that DOX loaded in functionalized MSNs presented the longer circulation time and lower plasma clearance rate compared with DOX solution. These results indicated that PEG/IDA modified MSNs with pH-responsive release capacity possessed great promising as an anticancer drug delivery system.

Fluorescent colorimetry test papers are promising for the assays of environments, medicines, and foods by the observation of the naked eye on the variations of fluorescence brightness and color. Unlike dye-absorption-based pH test paper, however, the fluorescent test papers with wide color-emissive variations with target dosages for accurate quantification remain unsuccessful even if the multicolorful fluorescent probes are used. Here, we report the dosage-sensitive fluorescent colorimetry test paper with a very wide/consecutive “from red to cyan” response to the presence and amount of arsenic ions, As(III). Red quantum dots (QDs) were modified with glutathione and dithiothreitol to obtain the supersensitivity to As(III) by the quenching of red fluorescence through the formation of dispersive QDs aggregates. A small amount of cyan carbon dots (CDs) with spectral blue-green components as the photostable internal standard were mixed into the QDs solution to produce a composited red fluorescence. Upon the addition of As(III) into the sensory solution, the fluorescence color could gradually be reversed from red to cyan with a detection limit of 1.7 ppb As(III). When the sensory solution was printed onto a piece of filter paper, surprisingly a serial of color evolution from peach to pink to orange to khaki to yellowish to yellow-green to final cyan with the addition of As(III) was displayed and clearly discerned the dosage scale as low as 5 ppb. The methodology reported here opens a novel pathway toward the real applications of fluorescent test papers.

•A single nanofluorophore probe with the dual-emissive intensities was designed.•The ratiometric probe produced the wide/consecutive color variations by analyte.•High-quality fluorescent colorimetric test papers sensitively responded to glucose.•The test papers gave a clear judgment whether blood glucose is at a normal level.Fluorescent test papers are promising for the wide applications in the assays of diagnosis, environments and foods, but unlike classical dye-absorption-based pH test paper, they are usually limited in the qualitative yes/no type of detection by fluorescent brightness, and the colorimetry-based quantification remains a challenging task. Here, we report a single dual-emissive nanofluorophore probe to achieve the consecutive color variations from blue to red for the quantification of blood glucose on its as-prepared test papers. Red quantum dots were embedded into silica nanoparticles as a stable internal standard emission, and blue carbon dots (CDs) were further covalently linked onto the surface of silica, in which the ratiometric fluorescence intensity of blue to red is controlled at 5:1. While the oxidation of glucose induced the formation of Fe3+ ions, the blue emission of CDs was thus quenched by the electron transfer from CDs to Fe3+, displaying a serial of consecutive color variations from blue to red with the dosage of glucose. The high-quality test papers printed by the probe ink exhibited a dosage-sensitive allochromatic capability with the clear differentiations of ~5, 7, 9, 11 mM glucose in human serum (normal: 3–8 mM). The blood glucose determined by the test paper was almost in accordance with that measured by a standard glucometer. The method reported here opens a window to the wide applications of fluorescent test paper in biological assays.

Penicilloic acid (PA) is a degraded byproduct of penicillin and often causes fatal allergies to humans, but its rapid detection in penicillin drugs remains a challenge due to its similarity to the mother structure of penicillin. Here, we reported a ligand-replaced molecularly imprinted monolayer strategy on a surface-enhanced Raman scattering (SERS) substrate for the specific recognition and rapid detection of Raman-inactive PA in penicillin. The bis(phenylenediamine)–Cu2+–PA complex was first synthesized and stabilized onto the surface of silver nanoparticle film that was fabricated by a bromide ion-added silver mirror reaction. A molecularly imprinted monolayer was formed by the further modification of alkanethiol around the stabilized complex on the Ag film substrate, and the imprinted recognition site was then created by the replacement of the complex template with Raman-active probe molecule p-aminothiophenol. When PA rebound into the imprinted site in the alkanethiol monolayer, the SERS signal of p-aminothiophenol exhibited remarkable enhancement with a detection limit of 0.10 nM. The imprinted monolayer can efficiently exclude the interference of penicillin and thus provides a selective determination of 0.10‰ (w/w) PA in penicillin, which is about 1 order of magnitude lower than the prescribed residual amount of 1.0‰. The strategy reported here is simple, rapid and inexpensive compared to the traditional chromatography-based methods.

Nowadays there is growing concern about the adulteration of synthetic anorexics in natural slimming products (NSP) due to the increasing use of weight-reducing aids. Here, we report surface-enhanced Raman spectroscopy (SERS) coupled with chemometrics for rapid discrimination and detection of sibutramine (SIB) and its analogues (mono-desmethylsibutramine, MDS; di-desmethylsibutramine, DDS) in konjac pressed candy (KPC), which is a NSP used in the treatment of obesity. It has been demonstrated that the two characteristic peaks at 1060 cm−1 (in SERS spectrum of SIB) and 1407 cm−1 (in SERS spectrum of MDS) were used to discriminate between SIB, MDS and DDS. Moreover, the two spectra for KPC with MDS and KPC with DDS only exhibited some slight differences. After the second derivative transformation, the differences were much more clear, especially for the peak at 1407 cm−1 in the SERS spectrum of KPC with MDS. Meanwhile, partial least-squares regression was used for quantitative analysis of the samples. The limit of detection for SIB, MDS and DDS was 5.00 × 10−8 M, 5.00 × 10−7 M and 1.00 × 10−6 M, respectively. Compared with previously reported studies, the method is simple (no pretreatment), less time-consuming and inexpensive, and can be applied to rapidly screen SIB and its analogues in NSP.

The adulteration of traditional Chinese medicine (TCM) with synthetic drugs severely harms the TCM effect and public health. Thus, quick detection of synthetic drug found in TCM is crucial. Here, we report surface-enhanced Raman scattering (SERS) coupled with density functional theory (DFT) calculations for the direct identification and detection of aminopyrine (AP) in TCM using silver-coated gold nanoparticles (Au@Ag NPs). It has been demonstrated that the Raman enhancement of Au@Ag NPs to AP was stronger than that of Au, Ag and Ag@Au NPs, and there was a strong dependence of the Raman enhancement on the substrate concentration. Moreover, we obtained the DFT calculation result of AP and found that the calculation result was in good agreement with the experimental one. In addition, the characteristic peak at 999 cm−1, which was the strongest peak in the SERS spectra, was used for a quantitative evaluation of the AP level. The limit of detection (LOD) was 2.50 × 10−7 M (equal to 57.8 ng mL−1) in aqueous solution, which was in the same order of magnitude as that obtained by liquid chromatography-mass spectrometry (LC-MS), and the recovery of AP ranged from 93.9% to 101% in the spiked TCM (Shexiang Fengshi capsule) sample. Each test using the SERS sensor only needed a 10 μL sample solution and the whole test could be accomplished within ∼3 min. The SERS technique can be applied to authenticate and detect trace AP in real herbal products.

•We developed a structure-selective hotspot Raman enhancement strategy to detect PA.•Interparticle hotspot is caused by the interaction of two carboxyls of PA with Au@Ag NPs.•The hotspot can selectively enhance the Raman signals of PA in penicillin matrix.•Rapid monitoring of allergen in penicillin will reduce the occurrence of allergic reaction.Trace penicilloic acid allergen frequently leads to various fatal immune responses to many patients, but it is still a challenge to directly discriminate and detect its residue in penicillin by a chemosensing way. Here, we report that silver-coated gold nanoparticles (Au@Ag NPs) exhibit a structure-selective hot-spot Raman enhancement capability for direct identification and detection of trace penicilloic acid in penicillin. It has been demonstrated that penicilloic acid can very easily link Au@Ag NPs together by its two carboxyl groups, locating itself spontaneously at the interparticle of Au@Ag NPs to form strong Raman hot-spot. At the critical concentration inducing the nanoparticle aggregation, Raman-enhanced effect of penicilloic acid is ~60,000 folds higher than that of penicillin. In particular, the selective Raman enhancement to the two carboxyl groups makes the peak of carboxyl group at C6 of penicilloic acid appear as a new Raman signal due to the opening of β-lactam ring of penicillin. The surface-enhanced Raman scattering (SERS) nanoparticle sensor reaches a sensitive limit lower than the prescribed 1.0‰ penicilloic acid residue in penicillin. The novel strategy to examine allergen is more rapid, convenient and inexpensive than the conventional separation-based assay methods.

Molecularly imprinted fluorescence sensors operate on the basis of the recognition of imprinted sites to guest and the resultant changes of fluorescence emission have been studied. However, the origin of guest-induced fluorescence enhancement and the function of host molecule are still unclear in theory. In this work, we have first designed three isomers, 2-acrylamidoquinoline, 3-acrylamidoquinoline and 8-acrylamidoquinoline, with weak fluorescence emission, and used them as both functional monomers and signaling units in molecularly imprinted fluorescence sensors. Quantum chemical calculation within the density functional theory (DFT) framework has been introduced to accurately evaluate and predict the hydrogen bonding interaction between these monomers and the analyte melamine. As a result, the as-synthesized 2-acrylamidoquinoline exhibits a highest hydrogen bonding ability and the ideal molar ratio of monomer to template is 3:1 in molecularly imprinted polymers, which can greatly enhance the fluorescence emission of functional monomer after guest-host binding due to the strong hydrogen bonding restriction to the transformation of monomer conformations. The prediction is in good agreement with the experimental observation. Moreover, the imprinted nanoparticles display significant fluorescence enhancement upon titration with different concentrations of melamine in methanol. The fluorescence sensors can be applied to detect the melamine in dairy products with a low limit of quantification of 0.5 μM. The results reported herein supply an excellent model for the design of molecularly imprinted fluorescence sensors and their prediction of chemical sensitivity to nonfluorescent compounds.

Six water-soluble phenylpropanoid compounds obtained from Rhodiola crenulata (R. crenulata) were fractionated by high-speed counter-current chromatography (HSCCC), and purified by semi-preparative high-performance liquid chromatography (Semi-prep HPLC). The purities of the six compounds were all above 98.0% and their structures were identified by spectroscopic methods. Among them, a new compound, 2-(4-hydroxyphenyl)-ethyl-O-β-d-glucopyranosyl-6-O-β-d-glucopyranoside (1), together with two known phenylpropanoids, p-hydroxyphenacyl-β-d-glucopyranoside (3) and picein (4) were isolated from R. crenulata for the first time. Meanwhile, the contents of six isolated ingredients from the crude extract of R. crenulata had been simultaneously detected, with satisfactory results. Furthermore, the antioxidant activities of the six compounds were accessed by measuring the radical scavenging activity against 2,2-diphenyl-1-picrylhydrazy (DPPH), and four compounds exhibited potent antioxidative activity.Highlights► Six water-soluble phenylpropanoids including a new phenylpropanoid (compound 1) were isolated from Rhodiola crenulata. ► Compound 1 was mainly elucidated by its 1D and 2D NMR spectral data and chemical method. ► The contents of six water-soluble phenylpropanoids from the crude extract of R. crenulata were simultaneously analysed by HPLC. ► Free radical scavenging capacities of the six water-soluble phenylpropanoids were first evaluated by DPPH test. ► The four phenylpropanoids from R. crenulata had potentials as natural antioxidants.

This paper reports a surface molecular self-assembly strategy for molecular imprinting on magnetic nanoparticles for selective separation and detection of estrogens in feeds. First, γ-methacryloxypropyltrimethoxysilane (MEMO) was successfully assembled at the surface magnetic nanoparticles through simple free radical polymerization, and subsequently, the copolymerization was further assembled between methacrylic acid (MAA) and ethylene glycol dimethacrylate (EGDMA) in the presence of templates 17β-estradiol (E2). The synthesized magnetic molecularly imprinted polymers for E2 (E2-MMIPs) showed quick separation, large adsorption capacity, high selectivity and fast binding kinetics for E2. Meanwhile, a dispersive solid-phase extraction (DSPE) based on E2-MMIPs has been established for efficient separation and fast enrichment of estrogens from the feeds. The assay exhibited a linear range of 0.1–4 μM for E2 and estriol (E3) with the correlation coefficient above 0.9996 and 0.9994, respectively. Recoveries of E2 from three kinds of feeds spiked at different concentration levels ranged from 92.7% to 97.0% with RSD < 4.7%, and recoveries of E3 ranged from 71.9% to 83.1% with RSD < 4.9%, respectively. The method is simple and sensitive, and can be used as an alternative tool to effectively separate and enrich the trace of estrogens in agricultural products by HPLC–UV.

This paper reports the preparation of metsulfuron-methyl (MSM) imprinted polymer layer-coated silica nanoparticles toward analysis of trace sulfonylurea herbicides in complicated matrices. To induce the selective occurrence of surface polymerization, the polymerizable double bonds were first grafted at the surface of silica nanoparticles by the silylation. Afterwards, the MSM templates were imprinted into the polymer-coating layer through the interaction with functional monomers. The programmed heating led to the formation of uniform MSM-imprinted polymer layer with controllable thickness, and further improved the reproducibility of rebinding capacity. After removal of templates, recognition sites of MSM were exposed in the polymer layers. As a result, the maximum rebinding capacity was achieved with the use of optimal grafting ratio. There was also evidence indicating that the MSM-imprinted polymer nanoparticles compared with nonimprinted polymer nanoparticles had a higher selectivity and affinity to four structure-like sulfonylurea herbicides. Moreover, using the imprinted particles as dispersive solid-phase extraction (DSPE) materials, the recoveries of four sulfonylurea herbicides determined by high-performance liquid chromatography (HPLC) were 80.2–99.5%, 83.8–102.4%, 77.8–93.3%, and 73.8–110.8% in the spiked soil, rice, soybean, and corn samples, respectively. These results show the possibility that the highly selective separation and enrichment of trace sulfonylurea herbicides from soil and crop samples can be achieved by the molecular imprinting modification at the surface of silica nanoparticles.

This paper reports the preparation of high density imprinted layer-coated silica nanoparticles toward selective recognition and fast enrichment of chlorpyrifos (CP) from complicated matrices. The molecularly imprinted polymers (MIPs) were successfully coated at the surface of modified silica through using the chemical immovable vinyl groups at the nanoparticles’ surface, followed by the graft copolymerization of methacrylic acid (MAA) and ethylene glycol dimethacrylate (EGDMA) in the presence of templates CP. It has been demonstrated that the space of end vinyl groups at the surface of silica can be controlled by changing the condition of chemical modification, regulating the thickness of imprinted shells and the density of efficient imprinted sites. After removal of templates by solvent extraction, the recognition sites of CP were created in the polymer coating layer. The CP-imprinted nanoparticles exhibited high recognition selectivity and binding affinity to CP analyte. When the CP-imprinted nanoparticles were used as dispersive solid-phase extraction (dSPE) materials, the high recovery yields of 76.1–93.5% from various spiked samples with only 1 μg/mL analyte were achieved by one-step extraction. These results reported herein provide the possibility for the separation and enrichment of CP from complicated matrices by the molecular imprinting modification at the surface of common silica nanoparticles.

This paper reports the molecularly imprinted layer-coated silica nanoparticles toward highly selective separation of active diosgenin (DG) from the crude extracts of Dioscorea nipponica Makino (DNM). It has been demonstrated that DG templates were efficiently imprinted into the silica layer by the use of thermally cleavable urethane bonds between DG and 3-isocyanatopropyltriethoxysilane (IPTS), which was synchronously coated onto the surface of silica mother nanoparticles through a seed-directing surface condensation reaction between DG-IPTS and tetraethoxysilicane (TEOS). After removal of templates by simple thermal cleavage reaction, a high density of recognition sites of DG were created in the silica-coating layer. Afterwards, the DG-imprinted silica nanoparticles were evaluated by rebinding experiments and showed a higher selectivity and affinity to DG than commercial silica. When the imprinted particles were used as solid-phase extraction (SPE) sorbents, the recovery yield of DG was up to 90% by one-step extraction from the hydrolysate of DNM, and the purity of DG was larger than 98% by HPLC analysis. These results reported herein provide the possibility for the highly selective separation and purification of active DG from DNM by the molecular imprinting modification at the surface of common silica adsorbents.

Molecularly imprinted hydrogel (MIH) as drug delivery system has been studied. It still remains a challenge to construct the stimuli-responsive MIH. Here, we report a coordinate bond strategy for imprinting doxorubicin (Dox) in hydrogel capable of pH-responsive and sustained drug delivery. The imprinting condition such as template–monomer interactions induced by metal ion was carefully investigated by spectroscopic methods. The obtained Dox–MIH was evaluated by absorption and in vitro release experiments. It has been demonstrated that the cupric ion mediated interaction between Dox and 4-vinyl pyridine via coordination and the optimal coordinate ratio of Dox/Cu2+ was 2:1. The rebinding amount of MIH to Dox was 2.7-fold that of nonimprinted hydrogel and the Dox-loaded MIH showed a pH-responsive release property. Not more than 10% of loaded drug was released from Dox–MIH at pH 7.2 during a time course of 7 days. However, near to 60% of loaded drug was sustainedly released at pH 5.0 during the same period. These results indicated that Dox–MIH with pH-responsive behavior possessed great promising as sustained-release delivery system of anticancer drug.

The adulteration of traditional Chinese medicine (TCM) with synthetic drugs severely harms the TCM effect and public health. Thus, quick detection of synthetic drug found in TCM is crucial. Here, we report surface-enhanced Raman scattering (SERS) coupled with density functional theory (DFT) calculations for the direct identification and detection of aminopyrine (AP) in TCM using silver-coated gold nanoparticles (Au@Ag NPs). It has been demonstrated that the Raman enhancement of Au@Ag NPs to AP was stronger than that of Au, Ag and Ag@Au NPs, and there was a strong dependence of the Raman enhancement on the substrate concentration. Moreover, we obtained the DFT calculation result of AP and found that the calculation result was in good agreement with the experimental one. In addition, the characteristic peak at 999 cm−1, which was the strongest peak in the SERS spectra, was used for a quantitative evaluation of the AP level. The limit of detection (LOD) was 2.50 × 10−7 M (equal to 57.8 ng mL−1) in aqueous solution, which was in the same order of magnitude as that obtained by liquid chromatography-mass spectrometry (LC-MS), and the recovery of AP ranged from 93.9% to 101% in the spiked TCM (Shexiang Fengshi capsule) sample. Each test using the SERS sensor only needed a 10 μL sample solution and the whole test could be accomplished within ∼3 min. The SERS technique can be applied to authenticate and detect trace AP in real herbal products.

Molecularly imprinted fluorescence sensors operate on the basis of the recognition of imprinted sites to guest and the resultant changes of fluorescence emission have been studied. However, the origin of guest-induced fluorescence enhancement and the function of host molecule are still unclear in theory. In this work, we have first designed three isomers, 2-acrylamidoquinoline, 3-acrylamidoquinoline and 8-acrylamidoquinoline, with weak fluorescence emission, and used them as both functional monomers and signaling units in molecularly imprinted fluorescence sensors. Quantum chemical calculation within the density functional theory (DFT) framework has been introduced to accurately evaluate and predict the hydrogen bonding interaction between these monomers and the analyte melamine. As a result, the as-synthesized 2-acrylamidoquinoline exhibits a highest hydrogen bonding ability and the ideal molar ratio of monomer to template is 3:1 in molecularly imprinted polymers, which can greatly enhance the fluorescence emission of functional monomer after guest-host binding due to the strong hydrogen bonding restriction to the transformation of monomer conformations. The prediction is in good agreement with the experimental observation. Moreover, the imprinted nanoparticles display significant fluorescence enhancement upon titration with different concentrations of melamine in methanol. The fluorescence sensors can be applied to detect the melamine in dairy products with a low limit of quantification of 0.5 μM. The results reported herein supply an excellent model for the design of molecularly imprinted fluorescence sensors and their prediction of chemical sensitivity to nonfluorescent compounds.