Self-Assembled Chromogenic Polymeric Nanoparticle-Laden Nanocarrier as a Signal Carrier for Derivative Binary Responsive Virus Detection.

In the current biosensor, the signal generation is limited to single virus detection in the reaction chamber. An adaptive strategy is required to enable the recognition of multiple viruses for diagnostics and surveillance. In this work, a nanocarrier is deployed to bring specific signal amplification into the biosensor, depending on the target viruses. The nanocarrier is designed using pH-sensitive polymeric nanoparticle-laden nanocarriers (PNLNs) prepared by sequential nanoprecipitation. The nanoprecipitation of two chromogens, phenolphthalein (PP) and thymolphthalein (TP), is investigated in three different solvent systems in which PNLNs demonstrate a high loading of the chromogen up to 59.75% in dimethylformamide (DMF)/dimethyl sulfoxide (DMSO)/ethanol attributing to the coprecipitation degree of the chromogens and the polymer. The PP-encapsulated PNLNs (PP@PNLNs) and TP-encapsulated PNLNs (TP@PNLNs) are conjugated to antibodies specific to target viruses, influenza virus A subtype H1N1 (IV/A/H1N1) and H3N2 (IV/A/H3N2), respectively. After the addition of anti-IV/A antibody-conjugated magnetic nanoparticles (MNPs) and magnetic separation, the enriched PNLNs/virus/MNPs sandwich structure is treated in an alkaline solution. It demonstrates a synergy reaction in which the degradation of the polymeric boundary and the pH-induced colorimetric development of the chromogen occurred. The derivative binary biosensor shows feasible detection on IV/A with excellent specificities of PP@PNLNs on IV/A/H1N1 and TP@PNLNs on IV/A/H3N2 with LODs of 27.56 and 28.38 fg mL-1, respectively. It intrigues the distinguished analytical signal in human serum with a variance coefficient of 25.8% and a recovery of 93.6-110.6% for one-step subtype influenza virus detection.

A novel phenolphthalein-based fluorescent sensor for Al3+ sensing in drinking water and herbal tea samples.

In this study, 3,3-bis(4-hydroxy-3-((E)-((4-hydroxyphenyl)imino)methyl) phenyl)isobenzofuran-1(3H)-one (HMBP) was designed as a ''turn-on″ fluorogenic chemosensor to detect Al3+. Studies were performed in C2H5OH-HEPES (v/v, 9/1, pH 7.0) media at λem = 475 nm. The LOD value was found to be 0.113 µM. The stoichiometric ratio of HMBP-Al3+ was determined as 1:2 by Job's plot and ESI-MS as well as 1H NMR titration. The binding constant of chemosensor HMBP with Al3+ from the Benesi-Hildebrand equation was determined to be 1.21 × 108 M-1. The quantum (Φ) yields were obtained as 0.040 and 0.775 for the chemosensor HMBP and HMBP-Al3+, respectively. The response of the chemosensor HMBP towards Al3+ was attributed to the strategies of blocking the photo-induced electron transfer (PET) and CN isomerisation mechanisms. Finally, the sensing of the chemosensor HMBP for the determination of Al3+ in real food samples, drinking waters and herbal teas, were employed.

Colorimetric detection of Staphylococcus aureus using gold nanorods labeled with yolk immunoglobulin and urease, magnetic beads, and a phenolphthalein impregnated test paper.

A colorimetric test is described for the rapid detection of Staphylococcus aureus (SA). Gold nanorods (AuNRs) are first labeled with urease and yolk immunoglobulin (IgY). This probe can specifically bind SA. In the next step, nonspecific magnetic beads and sample are added. This leads to the formation of the AuNR-IgY-SA-nMB immunocomplex which is then magnetically separated. Finally, a solution of urea is added to the supernatant. Ureases catalyzes the decomposition of urea which results in an increase in the pH value. The increase in the pH value is detected by using a phenolphthalein test paper which undergoes a color change from white to pink. The analytical process can be completed within 20 min. The method is highly specific and can detect as little as 476 cfu·mL-1. It was verified by analyzing contaminated Chinese cabbage and beef samples, and 1000 cfu·mL-1 of SA were accurately detected. Graphical abstract Schematic representation of a colorimetric method for the detection of Staphylococcus aureus based on the immunocomplex formed from dual-labeled gold nanorod (AuNR) probe, bacteria and non-specific magnetic bead (nMB). This method can be completed within 20 min.

A reversible calix[4]arene armed phenolphthalein based fluorescent probe for the detection of Zn2+ and an application in living cells.

A reversible and easy assembled fluorescent sensor based on calix[4]arene and phenolphthalein (C4P) was developed for selective zinc ion (Zn2+ ) sensing in aqueous samples. The probe C4P demonstrated high selective and sensitive detection towards Zn2+ over other competitive metal ions. Interaction of Zn2+ with a solution of C4P resulted in a considerable increment in emission intensity at 440 nm (λex  = 365 nm) due to the suppression of photoinduced electron transfer (PET) process and the restriction of C=N isomerization. The binding constant (Ka ) of C4P with Zn2+ was calculated to be 4.50 × 1011  M-2 and also the limit of detection of C4P for Zn2+ was as low as 0.108 µM (at 10-7  M level). Moreover, the fluorescence imaging in the human colon cancer cells suggested that C4P had great potential to be used to examine Zn2+ in vivo.

A phenolphthalein-based fluorescent probe for the sequential sensing of Al3+ and F- ions in aqueous medium and live cells.

A novel fluorescent probe, phenolphthalein­dialdehyde­(2­pyridyl) hydrazone (L), for sequentially detecting Al3+ and F- in almost 100% aqueous medium was successfully designed and synthesized. The probe offers two binding pockets for Al3+ to form a 1: 2 ligand/metal complex, leading to a significant fluorescence enhancement at 465 nm. Further, the in-situ formed L-Al complex acts as a secondary fluorescent chemosensor for F- by quenching the fluorescence of the complex with high selectivity. The detection limit for Al3+ and F- sensing is 2.28 nM and 0.13 µM, respectively, which are far below the World Health Organization (WHO) acceptable limits (7.41 µM for Al3+ ion and 79 µM for F-) in drinking water. The probe L was successfully applied to the detection of Al3+ and F- in cells using fluorescence microscopy.

Colorimetric Detection of Thiophenol Based on a Phenolphthalein Derivative and Its Application as a Molecular Logic Gate.

A phenolphthalein-based colorimetric probe bearing a dinitrobenzene group is reported as a thiophenol (PhSH)-selective chemodosimeter. PhSH can react with chemodosimeter 1 to afford phenolphthalein. The addition of PhSH to the aqueous solution of 1 followed by a change in pH of the resulting solution to basic induces a selective color change from colorless to pink. Furthermore, using PhSH and base as inputs and color change of 1 by naked eye as an output, leads to the construction of an AND logic gate.

Effect of different carboxylic acids in cyclodextrin functionalization of cellulose nanocrystals for prolonged release of carvacrol.

Current investigations deal with new surface functionalization strategy of nanocrystalline cellulose-based substrates to impart active molecule release properties. In this study, cellulose nanocrystals (CNC) were surface-functionalized with ß-cyclodextrin (ß-CD) using succinic acid (SA) and fumaric acid (FA) as bridging agents. The main objective of this surface modification performed only in aqueous media was to obtain new active materials able to release antibacterial molecules over a prolonged period of time. The reactions were conducted by immersing the CNC film into a solution composed of ß-CD, SA and FA, leading to CNC grafting. The materials were characterized by infrared spectroscopy (FT-IR), Quartz crystal microbalance-dissipation (QCM-D), AFM and phenolphthalein (PhP) was used to determine the efficiency of CNC grafting with ß-CD. The results indicated that ß-CD was successfully attached to the CNC backbone through the formation of ester bonds. Furthermore, carvacrol was entrapped by the attached ß-CD and a prolonged release was confirmed. In particular, CNC grafted to ß-CD in the presence of FA was selected as the best solution. The antibacterial activity and the controlled release were studied for this sample. Considerably longer bacterial activity against B. subtilis was observed for CNC grafted to ß-CD compared to CNC and CNC-FA, confirming the promising impact of the present strategy.

Adsorption properties of cross-linked cellulose-epichlorohydrin polymers in aqueous solution.

Cellulose was cross-linked with epichlorohydrin (EP) at variable levels (CLE-0.5, CLE-2 and CLE-4), where CLE-i denotes the cellulose to EP mole ratios. The cross-linked products were characterized by TGA and FT-IR spectroscopy, pH at the point of zero charge (pHpzc), water swelling, and dye-adsorption methods employing two types of dyes [phenolphthalein (phth) and p-nitrophenol (PNP)]. The characterization methods provide evidence of cross-linking of cellulose in accordance with variations in surface area, PZC, available surface hydroxyl groups, and thermal stability when compared against pristine cellulose. The pHpzc of the sorbent materials was ∼ 6.5 indicating a negative surface charge occurs above pHpzc. The cross-linked polymers possess greater swelling properties relative to pristine cellulose. Detailed adsorption studies were carried out at pH 9 for cellulose and CLE-i with five types single component carboxylate anions [2-hexyldecanoic acid (S1), trans-4-pentylcyclohexanecarboxylic acid (S2), 2-dicyclohexylacetic acid (S3), adamantane carboxylic acid (S4), and cyclohexane carboxylic acid (S5)] at 295 K. The uptake properties of PNP with cellulose and CLE-i were also compared at pH 5 and 9, respectively. CLE-2 had the highest uptake of PNP (Qm=1.22 × 10(-1)mmol/g, pH 9) and S1 (Qm=4.27 mg/g) while cellulose and CLE-4 had the strongest binding affinity (1.43 L/mmol and 5.90 × 10(-2)L/mg), respectively. Uptake of PNP by CLE-0.5 at pH 5 (Q m=5.30 × 10(-2)mmol/g) was higher than uptake at pH 9 (Qm=3.11 × 10(-2)mmol/g). Sorption of CLE-4 with S1, S2 and S3 showed that relative uptake of the surrogates had the following order: S3>S2>S1, where S2 had the strongest binding affinity to CLE-i. CLE-2 had the highest sorption capacity towards Si in an equimolar mixture with evidence of molecular selective uptake. At pH 9, low uptake was mainly related to electrostatic repulsion between the negatively charged sorbent surface and the carboxylate head groups of Si.

Cerenkov-specific contrast agents for detection of pH in vivo.

UNLABELLED: We report the design, testing, and in vivo application of pH-sensitive contrast agents designed specifically for Cerenkov imaging. Radioisotopes used for PET emit photons via Cerenkov radiation. The multispectral emission of Cerenkov radiation allows for selective bandwidth quenching, in which a band of photons is quenched by absorption by a functional dye. Under acidic conditions, (18)F-labeled derivatives emit the full spectrum of Cerenkov light. Under basic conditions, the dyes change color and a wavelength-dependent quenching of Cerenkov emission is observed. METHODS: Mono- and di-(18)F-labeled derivatives of phenolsulfonphthalein (phenol red) and meta-cresolsulfonphthalein (cresol purple) were synthesized by electrophilic fluorination. Cerenkov emission was measured at different wavelengths as a function of pH in vitro. Intramolecular response was measured in fluorinated probes and intermolecular quenching by mixing phenolphthalein with (18)F-FDG. Monofluorocresol purple (MFCP) was tested in mice treated with acetazolamide to cause urinary alkalinization, and Cerenkov images were compared with PET images. RESULTS: Fluorinated pH indicators were produced with radiochemical yields of 4%-11% at greater than 90% purity. Selective Cerenkov quenching was observed intramolecularly with difluorophenol red or monofluorocresol purple and intermolecularly in phenolphthalein (18)F-FDG mixtures. The probes were selectively quenched in the bandwidth closest to the indicator's absorption maximum (λmax) at pHs above the indicator pKa (the negative logarithm of the acid dissociation constant). Addition of acid or base to the probes resulted in reversible switching from unquenched to quenched emission. In vivo, the bladders of acetazolamide-treated mice exhibited a wavelength-dependent quenching in Cerenkov emission, with the greatest reduction occurring near the λmax. Ratiometric imaging at 2 wavelengths showed significant decreases in Cerenkov emission at basic pH and allowed the estimation of absolute pH in vivo. CONCLUSION: We have created contrast agents that selectively quench photons emitted during Cerenkov radiation within a given bandwidth. In the presence of a functional dye, such as a pH indicator, this selective quenching allows for a functional determination of pH in vitro and in vivo. This method can be used to obtain functional information from radiolabeled probes using multimodal imaging. This approach allows for the imaging of nonfluorescent chromophores and is generalizable to any functional dye that absorbs at suitable wavelengths.

Screening for multiple weight loss and related drugs in dietary supplement materials by flow injection tandem mass spectrometry and their confirmation by liquid chromatography tandem mass spectrometry.

A new method has been developed using flow injection tandem mass spectrometry to semi-quantitatively screen for weight loss drugs, including sibutramine, N-desmethylsibutramine, N-didesmethylsibutramine, and phenolphthalein in dietary supplements. Positive identification of these drugs in samples was further confirmed and quantified by liquid chromatography tandem mass spectrometry. The degradation products of sibutramine were observed and identified by LC-MS/MS which include N-desmethylsibutramine, N-didesmethylsibutramine, N-formyldesmethylsibutramine, and N-formyldidesmethylsibutramine.

Nanocontainer-based corrosion sensing coating.

The present paper reports on the development of new sensing active coating on the basis of nanocontainers containing pH-indicating agent. The coating is able to detect active corrosion processes on different metallic substrates. The corrosion detection functionality based on the local colour change in active cathodic zones results from the interaction of hydroxide ions with phenolphthalein encapsulated in mesoporous nanocontainers which function as sensing nanoreactors. The mesoporous silica nanocontainers are synthesized and loaded with pH indicator phenolphthalein in a one-stage process. The resulting system is mesoporous, which together with bulkiness of the indicator molecules limits their leaching. At the same time, penetration of water molecules and ions inside the container is still possible, allowing encapsulated phenolphthalein to be sensitive to the pH in the surrounding environment and outperforming systems when an indicator is directly dispersed in the coating layer.The performed tests demonstrate the pH sensitivity of the developed nanocontainers being dispersed in aqueous solutions. The corrosion sensing functionality of the protective coatings with nanocontainers are proven for aluminium- and magnesium-based metallic substrates. As a result, the developed nanocontainers show high potential to be used in a new generation of active protective coatings with corrosion-sensing coatings.

Color indicator for supramolecular polymer chemistry: phenolphthalein-containing thermo- and pH-sensitive N-(Isopropyl)acrylamide copolymers and ß-cyclodextrin complexation.

The copolymerization parameters of N-(isopropyl)acrylamide (1) and N-(2-hydroxy-5-(1-(4-hydroxyphenyl)-3-oxo-1,3-dihydroisobenzofuran-1-yl)benzyl)acrylamide (2) are determined. For both monomers, the homoaddition proceeds slightly faster than the heteroaddition step; however, the polymer formation occurs in a statistic fashion. Copolymers of different compositions are prepared and the cloud points are determined. Thereby, a significant influence of the concentration of monomer 2 and the pH value is found. For the first time, the complexation of polymer attached phenolphthalein by ß-cyclodextrins is shown. Furthermore, it is possible to achieve a decomplexation by the addition of suitable guest molecules. Both procedures can be followed with the naked eye.

Preparation of thermoresponsive Fe3O4/P(acrylic acid-methyl methacrylate-N-isopropylacrylamide) magnetic composite microspheres with controlled shell thickness and its releasing property for phenolphthalein.

In this work, Fe3O4/P(acrylic acid-methyl methacrylate-N-isopropylacrylamide) (Fe3O4/P(AA-MMA-NIPAm)) thermoresponsive magnetic composite microspheres have been prepared by controlled radical polymerization in the presence of 1,1-diphenylethene (DPE). The shell thickness of thermosensitive polymer (PNIPAm), which was on the surface of the microspheres, can be controlled by using DPE method. The morphology and thermosensitive properties of the composite microspheres, polymerization mechanism of the shell were characterized by TEM, FTIR, VSM, Laser Particle Sizer, TGA, NMR, and GPC. The microspheres with narrow particle size distribution show high saturation magnetization and superparamagnetism. The thermosensitive properties of the composite microspheres can be adjusted indirectly via controlling the addition amount of monomer (NIPAm) in the second step during controlled radical polymerization. Phenolphthalein was chosen as a model drug to investigate drug release behavior of the thermoresponsive magnetic composite microspheres with different shell thickness. Controlled drug release testing reveals that the release behavior depends on the thickness of polymer on the surface of the microspheres.

A novel eco-friendly technique for efficient control of lime water softening process.

Lime softening is an established type of water treatment used for water softening. The performance of this process is highly dependent on lime dosage. Currently, lime dosage is adjusted manually based on chemical tests, aimed at maintaining the phenolphthalein (P) and total (M) alkalinities within a certain range (2 P - M > or = 5). In this paper, a critical study of the softening process has been presented. It has been shown that the current method is frequently incorrect. Furthermore, electrical conductivity (EC) has been introduced as a novel indicator for effectively characterizing the lime softening process.This novel technique has several advantages over the current alkalinities method. Because no chemical reagents are needed for titration, which is a simple test, there is a considerable reduction in test costs. Additionally, there is a reduction in the treated water hardness and generated sludge during the lime softening process. Therefore, it is highly eco-friendly, and is a very cost effective alternative technique for efficient control of the lime softening process.

Rapid screening of illicit additives in weight loss dietary supplements with desorption corona beam ionisation (DCBI) mass spectrometry.

Desorption corona beam ionisation (DCBI), the relatively novel ambient mass spectrometry (MS) technique, was utilised to screen for illicit additives in weight-loss food. The five usually abused chemicals - fenfluramine, N-di-desmethyl sibutramine, N-mono-desmethyl sibutramine, sibutramine and phenolphthalein - were detected with the proposed DCBI-MS method. Fast single-sample and high-throughput analysis was demonstrated. Semi-quantification was accomplished based on peak areas in the ion chromatograms. Four illicit additives were identified and semi-quantified in commercial samples. As there was no tedious sample pre-treatment compared with conventional HPLC methods, high-throughput analysis was achieved with DCBI. The results proved that DCBI-MS is a powerful tool for the rapid screening of illicit additives in weight-loss dietary supplements.

The preparation and characterization of non-covalently functionalized graphene.

Recently, much work has focused on the exfoliation of graphene through a combination of oxidation and sonication procedures, followed by reduction through chemical methods. We demonstrated that the individual graphene oxide sheets can be readily reduced by using phenolphthalin as both reducing agent and stabilizer. The obtained non-covalently functionalized chemically reduced graphene oxide (CRG) can be dispersed in organic solvents very well, such as alcohol, N,N-dimethylformamide, N,N-Dimethylacetamide, N-methyl-2-pyrrolidone, etc., which can give practical applications in large scale production of oil dispersible graphene and have a potential in polymer nanocomposites fabrication.

Liposome solubilization induced by surfactant molecules in a microchip.

The dynamics of liposome solubilization was monitored by dynamic light scattering and optical microscopy. A newly designed Y-shape microchannel connected to a room was incorporated into a microchip and the reaction processes of the liposome suspension and surfactant solution were observed in the room after mixing the two fluids and stopping the flow. By using this microchip, we succeeded in real-time monitoring of liposome solubilization and the following dynamic processes of solubilization were proposed: 1) Deformed liposomes become spherical. 2) The liposome size increases until the surfactant/liposome ratio in the liposome membrane reaches a threshold value. 3) Mixed micelles of surfactants and phospholipids are released and the liposomes collapse.

Use of a pharmaceutically adulterated dietary supplement, Pai You Guo, among Brazilian-born women in the United States.

BACKGROUND: Pai You Guo is a weight loss supplement manufactured in China and adulterated with the banned pharmaceutical products sibutramine and phenolphthalein. The US Food and Drug Administration (FDA) announced a voluntary recall of Pai You Guo in 2009, yet clinicians have noted its continued use among Brazilian-born women in Massachusetts. OBJECTIVE: To assess prevalence of Pai You Guo use, associated side effects, modes of acquisition, and impact of FDA regulatory action on these outcomes. DESIGN: Cross-sectional study using an anonymous questionnaire. PARTICIPANTS: Women ≤60 years of age, born in Brazil who attended one primary care clinic or one of six churches in Massachusetts. MAIN MEASURES: Prevalence of use, how users first heard about the product, location of purchase, associated side effects, patterns of use before and after the FDA recall. KEY RESULTS: Twenty-three percent (130/565) of respondents reported using Pai You Guo. In multivariate analysis, obesity (adj OR 3.7, p-value <0.001) and lack of insurance (adj OR 2.6, p-value 0.005) were associated with use. The majority of users (85%) reported at least one side effect. Dry mouth (59%), anxiety (29%), and insomnia (26%) were most commonly reported adverse effects. Nearly thirty-percent of users (38/130) purchased Pai You Guo from local stores and 9% (11/130) purchased it over the Internet. The majority of respondents (79/130; 61%) purchased Pai You Guo after the FDA recall. No respondent was aware of the FDA recall. CONCLUSIONS: Use of this pharmaceutically adulterated supplement is common among Brazilian-born women in Massachusetts. The FDA alerts and recall did not appear to decrease its use.

A novel approach for determination of free fatty acids in vegetable oils by a flow injection system with manual injection.

A non-aqueous flow injection method for determining free fatty acid (FFA) content in corn and sunflower oil samples was developed. A single-line manifold system was built by modification of an HPLC for flow injection analysis (FIA). Without pre-treatment, oil samples were injected into a n-propanol solution containing KOH and phenolphthalein (PHP). The main parameters, such as flow rate of carrier phase, length, geometry, inner diameters of the coils and reagent concentration were all optimized. The proposed FIA method was validated for precision, accuracy, linear region, limit of detection (LOD) and limit of quantification (LOQ). The intra- and inter-day measurements of the precision of the method were found to be within the limits of acceptance criteria (RSD < 1%), and were rugged when the method was performed by a different analyst. The linear concentration range was calculated as 0.09-1.50 and 0.07-1.40 FFA% for corn and sunflower oils, correspondingly. The LOD and LOQ were found to be 7.53 × 10(-4)-2.28 × 10(-3) oleic acid % and 7.11 × 10(-4)-2.23 × 10(-3) oleic acid % for corn and sunflower oils, respectively. The results were compared with those obtained by the AOCS (Ca-5a-40) method using statistical t and F tests, and a significant difference was not observed between the methods at a 95% confidence level. The proposed method is suitable for quality control of routine applications due to its simplicity, high sample throughput, and economy of solvents and sample, offering considerable promise as a low cost analytical system that needs minimum human intervention over long periods of time.