Phenoxybenzoic Acid Research Articles

Repeated measurements and mixture effects of urinary bisphenols, parabens, polycyclic aromatic hydrocarbons, and other chemicals on biomarkers of oxidative stress in pre- and postpartum women

The association between oxidative stress and exposure to bisphenols, parabens, phenols, polycyclic aromatic hydrocarbons (PAH), and volatile organic compounds (VOCs) has been investigated by many in vitro and in vivo studies. However, most of these findings are based on cross-sectional studies, as a result of which the combined effects of these compounds have been rarely analyzed. In this study, our objective was to assess urinary bisphenols, parabens, PAHs, and VOCs, in relation to oxidative stress during pre-and postpartum periods, analyze the association between these chemicals and oxidative stress via repeated measurements using a linear mixed model (LMM), and evaluate the combined effects exerted by these chemicals on oxidative stress using Bayesian Kernel Machine Regression (BKMR). A total 529 urine samples were collected from 242 pregnant women during the 1st and 2nd trimesters, as well as postpartum follow-ups. Three bisphenols, four parabens, benzopheone-3 (BP-3), triclosan (TCS), four PAHs, two VOCs, and 3- phenoxy-benzoic acid (3-PBA) were analyzed. We also measured 8-hydroxydeoxyguanosine (8-OHdG) and malondialdehyde (MDA), which serve as oxidative stress biomarkers in maternal urine samples. During this period, 8-OHdG decreased steadily, whereas MDA increased during pregnancy and decreased after childbirth. LMM indicated that Bisphenol A, Prophyl-paraben, BP-3, and 1-hydroxypyrene (1-OHP) showed a significant association with increased MDA levels. The BKMR models revealed that the mixture effect exerted by these 16 chemicals had changed MDA levels, which indicate oxidative stress, and that both Butyl Paraben (BP) and 1-hydroxypyrene (1-OHP) had contributed to such oxidative stress. Mixtures of each subgroup (bisphenols, parabens, and PAHs) were associated with increased MDA levels. These findings suggest that exposure to some phenols and PAHs during pre- and post-partum stages may cause oxidative stress, and that exposure to these chemicals should be minimized during this period.

A New Class of Diaryl Ether Herbicides: Structure-Activity Relationship Studies Enabled by a Rapid Scaffold Hopping Approach.

We report on the development of a novel class of diaryl ether herbicides. After the discovery of a phenoxybenzoic acid with modest herbicidal activity, optimization led to several molecules with improved control of broadleaf and grass weeds. To facilitate this process, we first employed a three-step combinatorial approach, then pivoted to a one-step Ullmann-type coupling that provided faster access to new analogs. After determining that the primary target site of our benchmark diaryl ethers was acetolactate synthase (ALS), we further leveraged this copper-catalyzed methodology to conduct a scaffold hopping campaign in the hope of uncovering an additional mode of action with fewer documented cases of resistance. Our comprehensive and systematic investigation revealed that while the herbicidal activity of this area seems to be exclusively linked to ALS inhibition, our molecules represent a structurally distinct class of Group 2 herbicides. The structure-activity relationships that led us to this conclusion are described herein.

Characterization of multiple pesticide exposure in pregnant women in Brittany, France.

France is one of the biggest users of pesticides in Europe and exposure to pesticides is a current concern, especially when it occurs early in life. The aim of this study was to assess the exposure of pregnant women in Brittany (western France) with high pesticide use. The pesticides were selected according to agricultural practices. Forty pesticides or metabolites were measured in urine samples collected in 2004 from 296 pregnant women in Brittany. The samples were analyzed by ultra-high performance liquid chromatography (UHPLC) coupled to high resolution mass spectrometry (HRMS) after a solid phase extraction (SPE) step. Twenty seven pesticides were detected: the most frequently detected were the metabolites of organophosphate and pyrethroid insecticides (>89%) and several herbicides (phenoxypropionic acid derivatives and fluazifop >60%). Organophosphate and pyrethroid metabolites were also quantified in highest levels with maximum values of 590 μg/l for dimethylphosphate and 5.4 μg/l for 3- phenoxybenzoic acid. For the other parent compounds, such as prochloraz, bromoxynil and procymidone, they were also detected in 10-29% of the samples. Our results are consistent with pesticide use at the time of collection. The median concentrations of organophosphorus and pyrethroids were of the same order of magnitude as those reported in other countries. Herbicides and fungicides (fluazifop-p-butyl, bromoxynil, and prochloraz) were measured for the first time in this biomonitoring study, showing the usefulness of measuring widely used pesticides locally to improve knowledge of exposure. The objective of this study is to assess the exposure of pregnant women in a region of Europe with high pesticide use.

A Tiered Approach for Assessing Individual and Combined Risk of Pyrethroids Using Human Biomonitoring Data.

Pyrethroids are a major insecticide class, suitable for biomonitoring in humans. Due to similarities in structure and metabolic pathways, urinary metabolites are common to various active substances. A tiered approach is proposed for risk assessment. Tier I was a conservative screening for overall pyrethroid exposure, based on phenoxybenzoic acid metabolites. Subsequently, probabilistic approaches and more specific metabolites were used for refining the risk estimates. Exposure was based on 95th percentiles from HBM4EU aligned studies (2014–2021) covering children in Belgium, Cyprus, France, Israel, Slovenia, and The Netherlands and adults in France, Germany, Israel, and Switzerland. In all children populations, the 95th percentiles for 3-phenoxybenzoic acid (3-PBA) exceeded the screening value. The probabilistic refinement quantified the risk level of the most exposed population (Belgium) at 2% or between 1–0.1% depending on the assumptions. In the substance specific assessments, the 95th percentiles of urinary concentrations in the aligned studies were well below the respective human biomonitoring guidance values (HBM-GVs). Both information sets were combined for refining the combined risk. Overall, the HBM data suggest a low health concern, at population level, related to pyrethroid exposure for the populations covered by the studies, even though a potential risk for highly exposed children cannot be completely excluded. The proposed tiered approach, including a screening step and several refinement options, seems to be a promising tool of scientific and regulatory value in future.

Effects of 3-PBA on Complete Blood Count (CBC) and Liver Enzyme in Human: The Second Korean National Environmental Health Survey (KONEHS)

Pyrethroid were synthetic analogues insecticides as pyrethrins. They are known to be effective in insects because they are degraded by rapid metabolism in mammals. However, health effects that occur are not clearly known in human. In this study, we evaluated the effect of exposure of low concentrations of insecticide, rather than high concentration exposure, on human health.This study was performed on 5474 adults aged 19 years and older based on the Second Korean National Environmental Health Survey(KoNEHS 2012–2014). We used regression analysis to examine the effects of 3-PBA(phenoxybenzoic acid, as metabolite of pyrethroid) levels in urine on the complete blood count(CBC; white blood cell, red blood cell, hemoglobin, and platelet) and liver enzymes(AST, ALT, Γ-GPT). As clinical laboratory values are different according to sex, they are stratified. Thus, urinary 3-PBA/Cr, liver enzymes were transformed logarithmically due to their skewed distribution.Geometric mean concentrations of urinary 3-PBA were 1.94μg/L/Cr in total, 1.59μg/L/Cr in men, and 2.41μg/L/Cr in female, respectively. Association between log-transformed urinary 3-PBA and liver enzymes were not statistically significant. However, association between log-transformed urinary 3-PBA and RBC and hemoglobin were statistically significant, respectively (adjusted coefficient=-0.018(0.009), p=0.0425;-0.043(0.025) p=0.0791). After stratification, there was a negative association between log-transformed urinary 3-PBA and RBC and hemoglobin only for male group (adjusted coefficient=-0.024(0.035), p=0.0385;-0.097(0.011) p=0.0064).Low concentrations of pyrethroid exposure showed a statistically significant decrease in RBC and hemoglobin in humans. Liver enzymes, however, tended to increase, although not statistically significant. The results of this study need to educate the public about not being exposed to pesticides, and in order to do so, we must try to find these exposure factors in our living environment.

Phytotoxicity of pyrethroid pesticides and its metabolite towards Cucumis sativus

Pyrethroid pesticides residues have been frequently detected in soils and have been recognized to contribute to soil toxicity. The phytotoxic impact of pesticides was evaluated in Cucumis sativus (C. sativus) seeds. Percentage of seed germination, root elongation, shoot length and leaf length were considered as endpoints to assess the possible acute phytotoxicity of soil by the exposure to pyrethroid pesticides (cypermethrin, deltamethrin and cyhalothrin) and its metabolite phenoxybenzoic acid (3-PBA), in a concentration range between 50 and 500μgkg−1. For germination percentage, it was only observed a negative impact when seeds were exposed to the metabolite. Cypermethrin showed impact in the three studied endpoints of seed development, while deltamethrin merely affected the root length. Concerning pigments content, it can be said that chlorophylls and total carotenoids median values increased for cypermethrin and deltamethrin. This increase was more pronounced to deltamethrin in joint effect with the organic solvent dimethyl sulphoxide (DMSO). When exposed to cyhalothrin and 3-PBA, no statistically significant differences were observed for C. sativus seeds to all the assessed endpoints of seed development and the investigated pigments content. This research brings new data concerning the relative sensitivity of C. sativus seeds to pyrethroids pesticides commonly found in agricultural facilities, as well as critical understanding and development of using C. sativus for phytotoxicity assessments efforts for pesticide exposures.

Isolation of broad-specificity domain antibody from phage library for development of pyrethroid immunoassay

An antibody to phenoxybenzoic acid (PBA), the conserved chemical region of pyrethroids, was developed using a domain antibody (DAB) library to enable pyrethroid detection in agricultural products. The DAB library, constructed without animal immunization and based on a human VH framework, displayed repertoires on filamentous bacteriophage. After four rounds of panning, we obtained five domain antibodies that are capable of binding to PBA. Antibody A3 has strong identification capability to cypermethrin, β-cypermethrin, and fenvalerate. The antibody A3 was used to develop an enzyme-linked immunosorbent assay (ELISA). The IC50 values were 2.586, 1.814, and 2.251 μg/ml for cypermethrin, β-cypermethrin, and fenvalerate, respectively. The assay shows weak competition with flucythrinate but shows no competition with fenpropathrin, deltamethrin, and permethrin. The developed ELISA process was successfully applied to fortified Chinese cabbage samples, with the recoveries of cypermethrin, β-cypermethrin, and fenvalerate ranging from 84.4 to 112.3%. We developed an immunoassay to detect pyrethroids depending on the domain antibody library, which overcomes the limitation of requiring protein antigen to immunize animals raising antibody.

Isolation and characterization of fenvalerate degrading strain and optimization of degradation conditions

Bacterial strain BFE-023 with high ability to degrade fenvalerate was isolated from garden soil which contaminated by pyrethroid pesticides. According to physiological and biochemical characteristics and 16 S r DNA sequence,the bacterial strain was identified as Bacillus licheniformis. The main factors influencing fenvalerate degradation were confirmed by using Plackett-Burman design,and the degradation condition was optimized with response surface method. Under the optimal conditions,the degradation of fenvalerate and the generation of 3- phenoxy benzoic acid( 3- PBA) were researched. The results showed that fenvalerate concentration,incubation time and ferric chloride content were the major factors which influencing fenvalerate degradation. In addition,the degradation rate of fenvalerate under the optimized conditions in 60 h reached88.71%,which was similar to predictive value from response surface model(88.78%). The concentration of 3-PBA in the degradation system of fenvalerate was increased obviously at first and then decreased gradually. It was proved that the strain BFE-023 could degrade the intermediate 3-PBA.

Relationship between Urinary Pesticide Residue Levels and Neurotoxic Symptoms among Women on Farms in the Western Cape, South Africa.

Background: This cross-sectional study aimed to investigate the relationship between urinary pesticide residue levels and neurotoxic symptoms amongst women working on Western Cape farms in South Africa. Method: A total of 211 women were recruited from farms (n = 121) and neighbouring towns (n = 90). Participant assessment was via a Q16 questionnaire, reporting on pesticide exposures and measurement of urinary OP metabolite concentrations of dialkyl phosphates (DAP) and chlorpyriphos, 3,5,6-trichloropyridinol (TCPY) and of pyrethroid (PYR) metabolite concentrations (3- phenoxybenzoic acid (3PBA), 4-fluoro-3-phenoxybenzoic acid (4F3PBA), cis-2,2-dibromovinyl-2,2-dimethylcyclopropane-1-carboxylic acid (DBCA), and the cis- and trans isomers of 2,2-dichlorovinyl-2,2-dimethylcyclopropane-1-carboxylic acid. Results: Median urinary pesticide metabolites were slightly (6%–49%) elevated in the farm group compared to the town group, with 2 metabolites significantly higher and some lower in the farm group. The prevalence of all Q16 symptoms was higher amongst farm women compared to town women. Three Q16 symptoms (problems with buttoning, reading and notes) were significantly positively associated with three pyrethroid metabolites (cis- and trans-DCCA and DBCA), although associations may due to chance as multiple comparisons were made. The strongest association for a pyrethroid metabolite was between problems with buttoning and DBCA (odds ratio (OR) = 8.93, 95% confidence interval (CI):1.71–46.5. There was no association between Q16 symptoms and OP metabolites. Conclusions: Women farm residents and rural women from neighbouring towns in the Western Cape are exposed to OP and PYR pesticides. The study did not provide strong evidence that pesticides are associated with neurotoxic symptoms but associations found could be explored further.

Identification and characterisation of Aedes aegypti aldehyde dehydrogenases involved in pyrethroid metabolism.

BackgroundPyrethroid insecticides, especially permethrin and deltamethrin, have been used extensively worldwide for mosquito control. However, insecticide resistance can spread through a population very rapidly under strong selection pressure from insecticide use. The upregulation of aldehyde dehydrogenase (ALDH) has been reported upon pyrethroid treatment. In Aedes aegypti, the increase in ALDH activity against the hydrolytic product of pyrethroid has been observed in DDT/permethrin-resistant strains. The objective of this study was to identify the role of individual ALDHs involved in pyrethroid metabolism.Methodology/Principal FindingsThree ALDHs were identified; two of these, ALDH9948 and ALDH14080, were upregulated in terms of both mRNA and protein levels in a DDT/pyrethroid-resistant strain of Ae. aegypti. Recombinant ALDH9948 and ALDH14080 exhibited oxidase activities to catalyse the oxidation of a permethrin intermediate, phenoxybenzyl aldehyde (PBald), to phenoxybenzoic acid (PBacid).Conclusions/SignificanceALDHs have been identified in association with permethrin resistance in Ae. aegypti. Characterisation of recombinant ALDHs confirmed the role of this protein in pyrethroid metabolism. Understanding the biochemical and molecular mechanisms of pyrethroid resistance provides information for improving vector control strategies.

Environmentally relevant mixing ratios in cumulative assessments: A study of the kinetics of pyrethroids and their ester cleavage metabolites in blood and brain; and the effect of a pyrethroid mixture on the motor activity of rats

National surveys of United States households and child care centers have demonstrated that pyrethroids are widely distributed in indoor habited dwellings and this suggests that co-exposure to multiple pyrethroids occurs in nonoccupational settings. The purpose of this research was to use an environmentally relevant mixture of pyrethroids to assess their cumulative effect on motor activity and develop kinetic profiles for these pyrethroids and their hydrolytic metabolites in brain and blood of rats. Rats were dosed orally at one of two levels (1.5× or 5.0× the calculated dose that decreases rat motor activity by 30%) with a mixture of cypermethrin, deltamethrin, esfenvalerate, cis-/trans-permethrin, and β-cyfluthrin in corn oil. At 1, 2, 4, 8, or 24h after dosing, the motor activity of each animal was assessed and the animals sacrificed. Concentrations of pyrethroids in brain and blood, and the following metabolites: cis-/trans-dichlorovinyl-dimethylcyclopropane-carboxylic acid, 3-phenoxybenzoic acid, 3-phenoxybenzyl alcohol, 4-fluoro-3-phenoxybenzoic acid, and cis-dibromovinyl-dimethylcyclopropane-carboxylic acid were determined using liquid chromatography tandem mass spectrometry (LC–MS/MS). Using this pyrethroid mixture in rats, the results suggest there is greater metabolism of trans-permethrin prior to entering the systemic circulatory system. All pyrethroids had tissue half-lives (t1/2) of less than 5h, excepting esfenvalerate in brain. At early time points, relative pyrethroid brain concentrations approximated their dose mixture proportions and a sigmoidal Emax model described the relationship between motor activity decrease and total pyrethroid brain concentration. In blood, the t1/2's of the cyclopropane metabolites were longer than the phenoxybenzoic metabolites. However, relative to their respective precursors, concentrations of the phenoxybenzoic acids were much higher than concentrations of the cyclopropane metabolites. Brain concentrations of all metabolites were low relative to blood concentrations. This implies limited metabolite penetration of the blood-brain barrier and little metabolite formation within the brain. In conclusion: toxicokinetic differences between the pyrethroids did not appear to be important determinants of their relative potency and their effect on motor activity was consistent with a pyrethroid dose additive model.

Flying-seed-like liquid crystals 3: new guideline for the induction of mesomorphism by using bulky groups instead of long alkyl chains

In our previous work, we synthesized a series of phthalocyanine-based flying-seed-like compounds, (nnnnPh-PhO)4444PcCu (n = 3, 2, 1 and 0 in nnnnnnnnnnnnnnnnnnnPh-PhO: a–d), and revealed that each of them shows a columnar liquid crystalline phase (Colho or Colrho) from rt to an extremely high temperature near 500 °C. Thus, we could obtain columnar liquid crystalline phases for discotic compounds by using bulky substituents (a–d) instead of long alkyl chains. In order to further study the utility of these bulky substituents (a–d) on the induction of mesomorphism for other shaped molecules, we have synthesized novel flying-seed-like calamitic phenoxybenzoic acid derivatives, nnnnnPh-PhOBA (3a–d), and their Mitsubishi-Mark-shaped terbium complexes, (nnnPh-PhOBA)333Tb·mmmMeOH (4a–d), in this work. Very interestingly, the mesomorphism of the phenoxybenzoic aids derivatives nnnnnPh-PhOBA (n = 0–3) was induced to show a mesophase (Mx) only by the bulky substituent d (n = 0), whereas the mesomorphism of their corresponding terbium complexes (nnnnnnnnnnnnnnnnnnPh-PhOBA)333333333333333333Tb(III) (n = 0–3) was induced to show rectangular columnar (Colr) mesophases by the bulky substituents c and d (n = 1, 0). On the other hand, the mesomorphism of the PcCu complexes (nnPh-PhOBA)44PcCu (n = 0–3) in our previous work was induced by all the bulky substituents a, b, c and d (n = 0–3). Thus, it becomes apparent that both calamitic and columnar mesomorphism can be induced by the substitution of bulky groups instead of long alkyl chains, and that the balance of the core size and the bulkiness of the substituents is very important to obtain mesomorphism in flying-seed-like compounds. We believe that this is a new guideline for the induction of mesomorphism by using bulky groups instead of long alkyl chains.

ChemInform Abstract: Synthesis and Evaluation of CS‐2100, a Potent, Orally Active and S1P3‐Sparing S1P1 Agonist.

AbstractThe route to the title agonist involves construction of the oxadiazole ring via esterification of key intermediate amidoxime (VII) with phenoxybenzoic acid (VIII) in the presence of WSC.HCl and HOBt.

Enzymes-based resistant mechanism in pyrethroid resistant and susceptible Aedes aegypti strains from northern Thailand

Previous studies have shown that permethrin resistance in our selected PMD-R strain of Aedes aegypti from Chiang Mai, Thailand, was associated with a homozygous mutation in the knockdown resistance (kdr) gene and other mechanisms. In this study, we investigated the metabolic mechanism of resistance of this strain compared to the PMD strain which is susceptible to permethrin. The permethrin susceptibility of larvae was determined by a dose-response bioassay. Two synergists, namely piperonyl butoxide (PBO) and bis(4-nitrophenyl)-phosphate (BNPP), were also added to determine if the resistance is conferred by oxidase or esterase enzymes, respectively. The LC(50) value for PMD-R (25.42 ppb) was ∼25-fold higher than for PMD (1.02 ppb). The LC(50) was reduced 3.03-fold in PMD-R and 2.27-fold in PMD when the oxidase inhibitor (PBO) was added, but little or no reduction was observed in the presence of BNPP, indicating that oxidative enzymes play an important role in resistance. However, the LC(50) previously observed in the heterozygous mutation form was reduced ∼eightfold, indicating that metabolic resistance is inferior to kdr. The levels of cytochrome P450 (P450) extracted from fourth instar larvae were similar in both strains and were about 2.3-fold greater in microsomal fractions than in crude supernatant and cytosol fractions. Microsome oxidase activities were determined by incubation with each of three substrates, i.e., permethrin, phenoxybenzyl alcohol (PBOH), and phenoxybenzaldehyde (PBCHO), in the presence or absence of nicotinamide adenine dinucleotide phosphate (NADPH), nicotinamide adenine dinucleotide (NAD(+)), PBO, and BNPP. It is known that hydrolysis of permethrin produces PBOH which is further oxidized to PBCHO by alcohol dehydrogenase (ADH) and then to phenoxybenzoic acid (PBCOOH) by aldehyde dehydrogenase (ALDH). When incubated with permethrin, a small amount of PBCOOH was detected in both strains (about 1.1-1.2 nmol/min/mg protein), regardless of the addition of NADPH. The addition of PBO resulted in about 70% and 50% reduction of PBCOOH in PMD and PMD-R, respectively. The addition of BNPP reduced PBCOOH about 50% and 35% in PMD and PMD-R, respectively. Using PBOH as substrate increased PBCOOH ∼16-fold and ∼40-fold in PMD and PMD-R, respectively. Using PBCHO as substrate increased PBCOOH ∼26-fold and ∼50-fold in PMD and PMD-R, respectively. The addition of NADPH, and particularly NAD(+), increased the level of PBCOOH. Together, the results have indicated the presence of a metabolic metabolism involving P450, ADHs, and ALDHs in both PMD and PMD-R strains, with greater enzyme activity in the latter.

Comparaison de l’excrétion urinaire de biomarqueurs d’exposition aux pyréthrinoïdes et aux pyréthrines chez les résidents de régions urbaine et rurale de la Province de Québec, Canada

Background Residents of rural (agricultural) areas are often suspected of being exposed to higher levels of pesticides than residents of urban areas. However, only a limited number of studies have specifically evaluated the impact of the geographical area of residence on pyrethroid and pyrethrin exposure in the general population. This study aimed at comparing the levels of biomarkers of exposure between an urban and rural, adult and children, population of the Province of Quebec, Canada. Methods A total of 154 urban (Montreal) and 154 rural (Monteregie) participants provided a complete overnight timed-urine collection and filled a self-administered questionnaire. Urine samples were analyzed for pyrethroid and pyrethrin metabolites: cis- and trans-dichloro- and cis-dibromo- vinyldimethylcyclopropane carboxylic acids, phenoxy- and fluorophenoxy-benzoic acids and chrysanthemum dicarboxylic acid. Amounts of metabolites (pmol/12 h par kilogram body weight) and their frequency of detection in the two populations were compared and interpreted with the help of the answers gathered by questionnaire. Results Adults and children from the rural area tended to excrete higher levels of the main urinary metabolites, the cis- and trans-dichlorovinyldimethylcyclopropane carboxylic acids and the phenoxybenzoic acid, than those living in the urban area. When the adults and children were combined, this difference was statistically significant for the phenoxybenzoic acid ( p = 0.020), marginally significant for the trans-dichlorovinyldimethylcyclopropane carboxylic acid ( p = 0.053) and nonsignificant for the cis-dichlorovinyldimethylcyclopropane carboxylic acid ( p = 0.158). The chrysanthemum dicarboxylic acid, the fluorophenoxybenzoic acid and the dibromovinyldimethylcyclopropane carboxylic acid were detected in much lower proportion but, in the case of the fluorophenoxybenzoic acid, the relative frequency of detection was statistically significantly higher ( p < 0.001) in the rural population. Conclusion The presence of a baseline level of biomarkers in the urban and rural population confirms the ubiquity of pyrethroids and pyrethrins in the environment. However, in the rural adult and infantile population under study, other factors possibly contributed to slightly increase exposure compared to the urban population, namely the use of mosquito repellents and household insecticides as reported by questionnaire.

Thin Films of Tb(pobz)3 (Hpobz = 2-phenoxybenzoic acid): Reactive CVD and Optical Properties

Thin films of aromatic terbium carboxylates are promising materials for application in different optical devices. However, thin films deposition of these compounds by common methods is almost impossible due to their low solubility in most common organic solvents and nonvolatility. In our previous work it was shown that thin films of one of the simplest aromatic terbium carboxylate Tb(bz)3 (Hbz - benzoic acid) can be obtained by the original approach based on the exchange reaction between volatile precursors - reactive CVD (RCVD). Herein we improved this approach and demonstrated its possibilities and advantages on deposition of thin films of new emissive material - Tb(pobz)3 (Hpobz - phenoxybenzoic acid). The bulk products and thin films of Tb(pobz)3, obtained by RCVD method were characterized by elemental analysis, IR-, Raman and photoluminescent spectroscopy as well as thin films were studied by AFM and SEM techniques.

5-(4-Phenoxyphenyl)-1,3,4-thiadiazol-2-amine

The title compound, C14H11N3OS, was synthesized by the reaction of phenoxy­benzoic acid and thio­semicarbazide. The thia­diazole ring makes dihedral angles of 0.99 (16) and 86.53 (18)°, respectively, with the benzene and phenyl rings. The dihedral angle between the benzene and phenyl rings is 87.17 (19)°. Intra­molecular C—H⋯S contacts are present. In the crystal, inter­molecular N—H⋯N hydrogen bonds link the mol­ecules.

Discovery of novel series of benzoic acid derivatives containing biphenyl ether moiety as potent and selective human β 3-adrenergic receptor agonists: Part IV

Identification and SAR study of novel series of β 3-AR agonists with benzoic acid are described. Conversion of ether linkage position of phenoxybenzoic acid derivative 2b led to compound 7b with moderate β 3-AR activity. Further modification in right, center and left parts of compound 7b was investigated to improve the β 3-AR potency and selectivity. Compounds 7g and 7k, with the bulky aliphatic-substituted group at 2-position of benzoic acid moiety, were identified as potent and selective β 3-AR agonists. In addition, in vivo efficacy of compounds 7g and 7k was exhibited on dog OAB model.

Polyclonal Antibody-Based Noncompetitive Immunoassay for Small Analytes Developed with Short Peptide Loops Isolated from Phage Libraries

To date, there are a few technologies for the development of noncompetitive immunoassays for small molecules, the most common of which relies on the use of anti-immunocomplex antibodies. This approach is laborious, case specific, and relies upon monoclonal antibody technology for its implementation. We recently demonstrated that, in the case of monoclonal antibody-based immunoassays, short peptide loops isolated from phage display libraries can be used as substitutes of the anti-immunocomplex antibodies for noncompetitive immunodetection of small molecules. The aim of this work was to demonstrate that such phage ligands can be isolated even when the selector antibodies are polyclonal in nature. Using phenoxybenzoic acid (PBA), a major pyrethroid metabolite, as a model system, we isolated the CFNGKDWLYC peptide after panning a cyclic peptide library on the PBA/anti-PBA immunocomplex. The sensitivity of the noncompetitive enzyme-linked immunosorbent assay (ELISA) setup with this peptide was 5-fold (heterologous) or 400-fold (homologous) higher than that of the competitive assay setup with the same antibody. Phage anti-immunocomplex assay (PHAIA) was also easily adapted into a rapid and highly sensitive dipstick assay. The method not only provides a positive readout but also constitutes a major shortcut in the development of sensitive polyclonal-based assays, avoiding the need of synthesizing heterologous competing haptens.

Microarray Immunoassay for Phenoxybenzoic Acid Using Polymer Encapsulated Eu:Gd2O3Nanoparticles as Fluorescent Labels

Currently, detection in microarray bioanalysis is based mainly on the use of organic dyes. To overcome photobleaching and spectral overlaps we applied a new type of fluorophore, crystalline europium-doped gadolinium oxide (Eu:Gd2O3) nanoparticles, as labels in immunoassay microarrays. The Eu:Gd2O3 nanoparticles synthesized by spray pyrolysis offer narrow red emission, large Stokes shift, photostable laser-induced fluorescence with a long lifetime (1 ms). The amino functionalization of the particles was achieved by poly(L-lysine) (PL) encapsulation. The formation of a stable PL shell was confirmed by TEM analysis, colloidal stability studies, and quantification of the surface reactive amino groups. The PL-encapsulated particles were covalently conjugated to antibodies and successfully applied as reporters in a competitive fluorescence microimmunoassay for phenoxybenzoic acid (PBA), a generic biomarker of human exposure to pyrethroid insecticides. Microarrays were fabricated by microcontact printing of BSA-PBA in line patterns (10 x 10 microm). Confocal fluorescence microscopy combined with internal standard (fluorescein) calibration was used for quantitative measurements. The microarray immunoassay demonstrated a limit of detection of 1.4 microg L(-1) PBA. This work suggests the potential application of lanthanide oxide nanoparticles as fluorescent probes in microarray and biosensor technology, immunodiagnostics, and high-throughput screening.