Current Pharmaceutical Analysis
·
2023
·Vol. 19
·期 6
·511-520
·
IF 0.6
Zhang Mengmeng,Zou Qiaogen
Background: Atopic dermatitis (AD) is an allergic skin disease that can be inherited. Crisaborole is a specific drug developed to deal with this disease. The compounds of 4-(4- Bromo-3-formyl-phenoxy)-benzonitrile and 4-(4-(4-bromo-3-formylphenoxy)-3- formylphenoxy) benzonitrile
are the representative impurities in the synthesis of Crisaborole active pharmaceutical in gradient (API). Owing to the genotoxic impurities that could lead to cancer and gene mutations, it is necessary to develop a simple, efficient, sensitive, and accurate method to detect these impurities.
In this study, the 4-(4-Bromo-3-formyl-phenoxy)-benzonitrile and 4-(4-(4- bromo-3-formylphenoxy)-3-formylphenoxy)benzo- nitrile present in Crisaborole API were detected using UPLC-MS/MS. Methods: The separation was made on a ZORBAX Eclipse XDB-Pheny column (4.6 mm ×75mm, 3.5
μm) with the mobile phase of acetonitrile solution containing 0.1% trifluoroacetic acid (A) and water containing 0.1% formic acid (B) in gradient elution mode. Quantification was performed using positive ion electrospray ionization (ESI), and the contents of two compounds were determined
using the multiple reaction monitoring (MRM) modes. Results: The quantitative analytical method was fully validated with respect to linearity (r > 0.9998), sensitivity, precision, accuracy (the average recovery of two impurities was 84.1% to 90.7%), and robustness. Conclusion:
Three batches of samples were detected by UPLC-MS/MS, indicating that the proposed approach was applicable for the quality evaluation of Crisaborole.
研究领域:
药物分析
·
皮肤病学
·
毒理学
✓ 已验证
DOI
高影响因子
CHINESE JOURNAL OF CHEMICAL ENGINEERING
·
2020
·
IF 2.627
Haiyan Zhou,Yizuo Li,Rui Jiang,Xianlin Wang,Yuanshan Wang,Yaping Xue,Yuguo Zheng
R -2-(4-hydroxyphenoxy)propionic acid ( R -HPPA) is a key intermediate for the synthesis of classic herbicides with high selectivity against grassy weed. The main route for R -HPPA biosynthesis is to hydroxylate the substrate R -2-phenoxypropionic acid ( R -PPA) at C-4 position with microbes. In order to provide sufficient R -PPA for the industrial production of R -HPPA, an effective R -PPA synthesis method was established and optimized in this work. The synthesis process mainly consisted of two steps: (1) synthesis of S -2-chloropropionic acid from L-alanine via diazotization and chlorination reactions; and (2) synthesis of R -PPA from S -2-chloropropionic acid and phenol via etherification reaction. The optimal reaction conditions were as follows: HCl: NaNO 2 : KI: L-Ala = 2.0: 1.2: 0.7: 1.0 (in molar), 125 °C reflux for 1.5 h, with KI as catalyst, and KI: S -2-chloropropionic acid: phenol = 0.075: 1.2: 1.0 (in molar). Under these conditions, an improved molar conversion rate (74.9%, calculated in phenol) was achieved. After extraction using anionic exchange resin Amberlite IRA-400 (CI), R -PPA product with a purity of 95.08% was obtained. The purified R -PPA was identified and evaluated in the application of the biotransformative production of R -HPPA. The results indicated that the synthesized R -PPA supported the R -HPPA biosynthesis with a comparable yield as that of the standard R -PPA. The R -PPA synthesis method provided herein exhibited the advantages of low price and easy availability of raw materials, less toxicity of reagents, simple manipulations, and low equipment/instrument requirements.
研究领域:
生物化学
·
有机化学
·
工业微生物学
✓ 已验证
产品关联
DOI
高影响因子
EUROPEAN POLYMER JOURNAL
·
2016
·
IF 3.485
Quan Yuan,Guo-Hua Sun,Ke-Fei Han,Jing-Hua Yu,Hong Zhu,Zhong-Ming Wang
A series of copolymers, which can also be regarded as ABPBIs containing phenoxyl in the main chain, were synthesized by copolymerization of two kinds of self-polycondensation monomers: 3,4-diaminobenzoic acid (DABA) and 4-(3,4-diamino-phenoxy)-benzoic acid (DPBA). The phenoxyl-containing ABPBIs exhibit better processability and acid stability than original ABPBI, despite their affinities towards acid decrease with the addition of phenoxyl moieties. By adjusting the phenoxyl content of the polymer, we made a tradeoff between acid doping levels and proton conductivity, with mechanical properties. The optimal polymer therein, PO-AB-50 (50 M percentages of DPBA in total monomers), exhibits considerable proton conductivity (53.47 mS/cm at 160 °C) and tensile strength (1.9 MPa) after doped with phosphoric acid. In addition, the oxidation stability, water uptake and swell ratio properties of the polymers were also improved with the introduction of phenoxyl moieties.
研究领域:
材料科学
·
化学工程
✓ 已验证
产品关联
DOI
高影响因子
BIOPROCESS AND BIOSYSTEMS ENGINEERING
·
2019
·Vol. 42
·期 10
·1573-1582
·
IF 2.371
Zhou Hai-Yan,Li Yi-Zuo,Jiang Rui,Hu Hai-Feng,Wang Yuan-Shan,Liu Zhi-Qiang,Xue Ya-Ping,Zheng Yu-Guo
R -2-(4-hydroxyphenoxy)propionic acid ( R -HPPA) is a key intermediate of the enantiomerically pure phenoxypropionic acid herbicides. R -HPPA could be biosynthesized through selective introduction of a hydroxyl group (–OH) into the substrate R -2-phenoxypropionic acid ( R -PPA) at C-4 position, facilitated by microorganisms with hydroxylases. In this study, an efficient high-throughput screening method for improved R -HPPA biosynthesis through microbial hydroxylation was developed. As a hydroxylated aromatic product, R -HPPA could be oxidized by oxidant potassium dichromate to form brown-colored quinone-type compound. The concentration of R -HPPA can be quantified according to the absorbance of the colored compound at a suitable wavelength of 570 nm; and the R -HPPA biosynthetic capability of microorganism strains could also be rapidly evaluated. After optimization of the assay conditions, the high-throughput screening method was successfully used in identification of Beauveria bassiana mutants with enhanced R -HPPA biosynthesis capacity. A positive mutant C-7 with high tolerance to 20 g/L R -PPA was rapidly selected from 1920 mutants. The biomass and R -HPPA titer were 12.5- and 38.19-fold higher compared with the original strain at 20 g/L R -PPA. This high-throughput screening method developed in this work could also be a potential tool for screening strains producing other important phenolic compounds.
研究领域:
生物技术
·
微生物学
·
化学工程
·
药学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
FUEL PROCESSING TECHNOLOGY
·
2016
·
IF 3.847
Mei-Xia Zhao,Xian-Yong Wei,Meng Qu,Zhan-Ku Li,Jing Liu,Yan Li,Jiao Kong,Wei Zhao,Zhi-Min Zong
A novel solid acid was prepared by impregnating trifluoromethanesulfonic acid (TFMSA) onto attapulgite powder (AP). Benzyloxybenzene (BOB) was used as a lignite-related model compound to evaluate the catalytic activity of TFMSA/AP for cleaving C alk –O bridged bonds in lignites. The results show that BOB was mainly hydrocracked to toluene, phenol , and (ethoxymethyl)benzene over TFMSA/AP in ethanol without adding gaseous hydrogen. In addition, ethanol participated in and significantly facilitated BOB hydrocracking . Based on the kinetic investigation, BOB hydrocracking over TFMSA/AP is absent of mass transfer limitations with the apparent activation energy of only 19.4 kJ mol − 1 , which is far smaller than the dissociation energy (209.2 kJ mol − 1 ) of C alk –O bridged bond in BOB. The proton transfer directly from TFMSA/AP and/or via ethanol dehydrogenation to the oxygen atom of BOB could be the crucial step for BOB hydrocracking over TFMSA/AP.
研究领域:
化学工程
·
催化科学
✓ 已验证
产品关联
DOI
高影响因子
Journal of Materials Research and Technology-JMR&T
·
2022
·
IF 6.267
Yiyang Chen,Hongjuan Wu,Rui Duan,Kailun Zhang,Weihua Meng,Yan Li,Hongqiang Qu
Sn-doped graphene nanoplatelets (GnPSn) was successfully synthesized by wet ball milling method from expandable graphite and Sn powder. The surface morphology, thickness, crystal structure and chemical structure were comprehensive characterized. Epoxy resin (EP) composites (EP/GnPSn or EP/HPCTP/GnPSn) were prepared by adding GnPSn alone or GnPSn and hexaphenoxy cyclotriphosphazene (HPCTP) together to EP to improve the fire resistance and smoke suppression. EP/6.3wt%HPCTP/2.7wt%GnPSn composite had the best flame retardancy with LOI value of 33.6%, UL-94 of V 0 grade, peak heat release rate and total heat release reduced by 44.80% and 23.93%, respectively. The results of thermogravimetry analysis, Raman spectroscopy and Fourier transform infrared spectroscopy showed that HPCTP and GnPSn can react to form Sn–O–P bonds to promote the compactness of the residual char in condensed phase, thereby preventing the combustion of EP matrix.
研究领域:
材料科学
·
化学工程
✓ 已验证
产品关联
DOI
高影响因子
JOURNAL OF POLYMER SCIENCE
·
2021
·Vol. 59
·期 13
·1434-1445
·
IF 0
Hongyu Jiang,Hanzhou Jiang,Guofei Chen,Xingzhong Fang
Two isomers of commercial 4,4′-(4,4′-isopropylidenediphenoxy) bis(phthalic anhydride) (4,4′-BPADA), that is, 3,4′-(4,4′-isopropylidenediphenoxy) bis(phthalic anhydride) (3,4′-BPADA) and 3,3′-(4,4′-isopropylidenediphenoxy) bis(phthalic anhydride) (3,3′-BPADA), were synthesized through aromatic nucleophilic substitution from nitrophthalonitrile and bisphenol A. 3,4′-BPADA was first synthesized from two intermediates, that is, 3-(4-[4-hydroxyphenylisopropylidene] phenoxy) phthalonitrile (3-BPADN) and 3,4′-(4,4′-isopropylidenediphenoxy) bis(phthalonitrile) (3,4′-BPATN). The corresponding three series of polyetherimides (PEIs) were prepared with two representative aromatic diamines (4,4′-oxydianiline and m -phenylenediamine ( m -PDA)) via two-step procedure and chemical imidization. Isomeric polyimides showed T g s from 206 to 256°C in nitrogen and T d5% s from 488 to 511°C in argon, good mechanical properties (tensile moduli of 2.3–3.3 GPa, tensile strengths of 70–96 MPa, and elongations at break of 3.2%–5.1%), and good solubility. With the introduction of 3-substituted phthalimide unit, PEIs displayed higher T g values, lower strengths and elongations, better solubility and larger d -spacings. The rheological properties of thermoplastic polyimide resins based on the BPADA isomers were investigated, which showed that polyetherimide PEI-3b derived from 3,3′-BPADA and m -PDA had the lowest melt viscosity among the isomers, indicating that the melt processibility had been greatly improved. Graphical
研究领域:
高分子化学
·
材料科学
·
高分子工程
✓ 已验证
DOI
FOOD AND CHEMICAL TOXICOLOGY
·
2023
·
IF 4.3
Yiwen Cui,Yingying Sun,Hang Yu,Yahui Guo,Weirong Yao,Yunfei Xie,Fangwei Yang
Pyrethroid insecticides (PIs), a class of structurally similar non-persistent organic pollutants, can be degraded and metabolized to more toxic, and longer half-life products. In this study, the binding interaction mechanisms between human serum albumin (HSA) and the main degradation metabolites of PIs, 3-phenoxybenzoic acid (3-PBA) and 4-fluoro-3-phenoxybenzoic acid (4-F-3-PBA), were studied by theoretical simulation and experimental verification. Steady state fluorescence spectra showed that the fluorescence quenching mechanism was static. According to the binding constant, 4-F-3-PBA (1.53 × 10 5 L mol −1 ) was bound more strongly to HSA than 3-PBA (1.42 × 10 5 L mol −1 ) in subdomain ⅡA (site I). It was found by isothermal titration calorimetry that the metabolites and HSA spontaneously combined mainly through hydrogen bond and van der Waals interaction . Ultraviolet absorption spectra and circular dichroism spectra showed that the metabolites caused slight changes in the microenvironment and conformation of HSA. The above results were proved by molecular docking. The toxicity properties of the metabolites were further analyzed by software, and 4-F-3-PBA was found to be more toxic than 3-PBA. Considering the high exposure level of these metabolites in food , the environment and human body, it is necessary to further explore the toxicity of PIs metabolites.
研究领域:
环境科学
·
毒理学
·
生物化学
·
分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Reaction Kinetics Mechanisms and Catalysis
·
2017
·Vol. 122
·期 1
·357-367
·
IF 1.264
Wu Shuxiang,Wang Wenhang,Fang Yuzhen,Kong Xiangjin,Liu Junhai
Silicotungstic acid (STA) modified ZIF-8 catalyst was developed by simple impregnation method for Friedel–Craft acylation reaction. The best performance was observed on 20 wt% STA/ZIF-8, over which conversion of anisole and selectivity towards p-benzoylanisole reached 99.2 and 93.5%, respectively. N 2 physisorption, XRD, FT-IR, TGA and Pyridine FT-IR characterizations indicated that introduction of STA to ZIF-8 did not change its main structure but increased its acid site density, which promised enhanced catalytic performance of the obtained catalyst. Moreover, the performance of the catalyst was further proved through a series of substrates with electron donor or withdraw substitution group, since all of substrates could be converted to corresponding p-isomer effectively.
研究领域:
化学
·
催化科学
✓ 已验证
DOI
高影响因子
BIOTECHNOLOGY AND APPLIED BIOCHEMISTRY
·
2019
·Vol. 67
·期 3
·343-353
·
IF 1.559
Hai-Feng Hu,Hai-Yan Zhou,Gao-Ping Cheng,Ya-Ping Xue,Yuan-Shan Wang,Yu-Guo Zheng
R -2-(4-hydroxyphenoxy)propionicacid (HPOPA) is a valuable intermediate for the synthesis of enantiomerically pure aryloxyphenoxypropionic acid herbicides. In this work, to improve the HPOPA biosynthesis by Beauveria bassiana ZJB16002 from the substrate R -2-phenoxypropionic acid (POPA), the original HPOPA producer B. bassiana ZJB16002 was subjected to physical mutagenesis with 137 Cs-γ irradiation and chemical mutagen N -methyl- N' -nitro- N -nitrasoguanidine (NTG) induced mutagenesis. The effects of different treatment doses of the mutagens on the lethal rate and positive mutation rate were investigated, and the results showed that the optimal 137 Cs-γirradiation dose and NTG concentration was 850 Gy and 500 µg/mL, respectively. Under these conditions, a mutant strain CCN-7 with the highest HPOPA production capacity was obtained through two rounds of 137 Cs-γ irradiation treatment followed by one round of NTG mutagenesis. At the substrate (POPA) concentration of 50 g/L, HPOPA titer of CCN-7 reached 36.88 g/L, which was 9.73-fold higher than the parental strain. The morphology of the wild-type and mutant strain was compared and the results might provide helpful information in exploration of the correlation of morphology and biochemical features of B. bassiana .
研究领域:
微生物学
·
生物工程
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF ENVIRONMENTAL MANAGEMENT
·
2022
·
IF 8.91
Kaidi Hu,Jianlong Li,Tianye Zhao,Qiao Zhou,Qin Li,Xinjie Hu,Guoquan Han,Shuhong Li,Likou Zou,Shuliang Liu
As a major intermediate metabolite of synthetic pyrethroids , the occurrence of 3-phenoxybenzoic acid hinders the decomposition of the parent pesticide and poses uncertain risks to environmental ecology and living organisms. Strain Aspergillus oryzae M-4 was previously reported to degrade 3-PBA and several substances were identified as downstream transformation products (TPs). But the mechanism underlying the cleavage of ether bond remains largely unclear. Here, we attempted to address such concern through identifying the peripheral TPs and analyzing transcriptomics, coupled with serial batch degradation experiments. Analysis results of chromatographic/mass spectrometry suggested that 3-PBA underwent twice hydroxylation , to yield mono- and dihydroxylated 3-PBA successively. In parallel, a mutual transformation between 3-PBA and 3-phenoxybenzyl alcohol (3-PBOH) also existed. The proposal of peripheral pathway represents an important advance towards fully understanding the whole 3-PBA metabolism in M-4. A specific altered metabolization was found for the first time, that is, resting cells of M-4 skipped the reduction step and initiate hydroxylation directly, by comparison with growing cells. Transcriptome analysis indicated that 3-PBA induced the up-regulation of genes related to energy investment, oxidative stress response, membrane transport and DNA repair. In-depth functional interpretation of differential expression genes suggested that the generation 3-PBOH and hydroxylated 3-PBA may be due to the participation of flavin-dependent monooxygenases (FMOs) and cytochrome P450 (CYP450), respectively. This study provides new insight to reveal the biodegradation mechanism of 3-PBA by A . oryzae M-4.
研究领域:
环境科学
·
微生物学
·
分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF HAZARDOUS MATERIALS
·
2023
·
IF 13.6
Shiyi Hu,Xin Jin,Mengwen Liu,Yao Li,Yadong Wang,Yixiong Wei,Pengkang Jin,Xiaochang C. Wang
The existence of dissolved organic matter (DOM) with low coagulability poses great challenges for conventional coagulation (CC) in water treatment . As a kind of typical organochlorine pesticide , 2,4-dichlorophenoxyacetic acid (2,4-D) cannot be efficiently removed by CC. To enhance the 2,4-D removal, ozonation was applied with coagulation. The hybrid ozonation-coagulation (HOC) achieved 60.61% DOC removal efficiency, which was obviously higher than pre-ozonation coagulation (POC) (45.83%). Synchronous fluorescence spectroscopy revealed stronger complexation between modified 2,4-D and coagulants during the HOC than that in subsequent coagulation of the POC process. During the HOC process, ozone promoted the formation of polymeric Al species, such as Al b . To investigate the 2,4-D removal mechanism, γ-Al 2 O 3 /O 3 process with the same oxidation ability as the HOC was established. 2,4-D was oxidized step-by-step to 2,4-dichlorophenol, 4,6-dichlororesorcin, 3,5-dichlorocatechol, 2-chlorohydroquinone, 4-chlorocatechol, 1,2,4,5-tetrahydroxybenzene, pentahydroxybenzene and oxalic acid in γ-Al 2 O 3 /O 3 process. However, during the HOC process, these oxidized intermediates were readily complexed by coagulants and accumulated in flocs. Especially 1,2,4,5-tetrahydroxybenzene and pentahydroxybenzene, completely complexed by AlCl 3 •6H 2 O hydrolysates as soon as being formed. Immediate entrapment and complexation between coagulant hydrolysates and 2,4-D oxidized intermediates inhibited the generation of small-molecular-weight organics such as oxalic acid, which enhanced the removal of organics with low coagulability.
研究领域:
环境科学
·
水处理工程
✓ 已验证
产品关联
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）