CHROMATOGRAPHIA
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2022
·Vol. 86
·期 2
·185-197
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IF 2.213
Lin Xinghua,Hao Gugu,Xu Guobin,Sun Fuzhou,Xin Libo,Wu Shuming,Wang Zhongqing,You Jinsong,Huang Fangfang,Song Xuezhi
An unknown peak with a relative retention time (RRT) of 1.47 was noticed in HPLC chromatograms for related substances of mirabegron extended-release tablets. The level of this unknown peak under the accelerated stability condition for 6 months was as high as 0.19%, which had a trend to exceed the identification threshold of 0.2% from ICH Q3B. The purpose of this study was to identify the RRT 1.47 impurity, and we studied its degradation mechanism to control its content to a lower level. The structure of the RRT 1.47 impurity was identified as a mirabegron dimer bridged by methylene via LC–MS and NMR. Investigation on compatibility of drug-excipients indicated that this impurity formed by Mannich reaction between mirabegron and residual formaldehyde in excipients polyethylene glycol (PEG), polyoxyethylene (PEO). Moreover, the determination of formaldehyde content in excipients further proved this speculation. There was a linear relationship between the amount of formaldehyde and the content of generated dimer impurity within a certain range. The reaction between mirabegron and formaldehyde at different temperatures demonstrated that the higher the temperature, the faster the reaction rate and the higher level of this impurity were generated. To understand the kinetics of the reaction, we calculated the rate of dimerization and also the activation energy of the process based on the stability data. During the development of pharmaceutical formulation on mirabegron or similar structure, appropriate excipients should be selected or the formaldehyde content in excipients could be controlled to avoid such reactions to improve the quality of the product.
研究领域:
药物化学
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制药工程
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DOI
高影响因子
CHEMICAL ENGINEERING JOURNAL
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2019
·
IF 8.355
Gang Wang,Zengxi Li,Liu Fan,Chunshan Li,Suojiang Zhang
S ec -amines catalyzed two-step Mannich reaction for preparation of methacrolein from propionaldehyde and formaldehyde was more attractive than the C 4 selective oxidation route. Herein, a novel continuous fixed-bed process was developed for direct preparation of methacrolein from above stocks with catalysis of sec -amine grafted D301 resin. The effect of resin, sec -amine structure and grafting percentage on catalytic performance of the modified resin were detailed investigated and demonstrated by using FT-IR, TG-DTA, titration and solid-state NMR characterization methods before the optimal conditions were obtained. The grafting percentage of amine with abundant sec -amino groups onto D301 resin could reach 93.7% at optimal condition. With this new strategy, the yield and selectivity of methacrolein could attain 40.2% and 99.3%. In addition, the Mannich reaction step with activation energy of 66.3 kJ/mol was determined as the rate-controlling step through mechanism-based kinetic calculation.
研究领域:
有机化学
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催化化学
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DOI
高影响因子
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
·
2024
·
IF 7.7
Xiuxian Zhao,Heng Zhao,Anna Mei,Lin Peng,Junhua Sun
Green and high-performance biomass-based adsorbents have a good application prospect for the removal of heavy metals. At present, the preparation of chitosan/lignin biomass adsorbents mainly adopts dissolution-drying method, and the obtained adsorbents show relatively poor adsorption performance for heavy metals. To overcome this problem, a novel chitosan/lignin hydrogel (CSL) is prepared by a simple one-pot method through the Mannich reaction. Research findings show that the hydrogels present higher adsorption selectivity for Pb(II) and Cu(II) than other common heavy metals. Among them, the optimal hydrogel CSL1 shows unexpectedly ultrafast adsorption rate for Pb(II) and Cu(II) with equilibrium time of only 1 min and 2 min. Meanwhile, the maximum adsorption capacities of CSL1 for Pb(II) and Cu(II) are 139.86 and 98.71 mg·g −1 , respectively. Compared with the reported adsorption materials related to chitosan or lignin, the CSL1 has the advantages of simple preparation process, considerable adsorption capacity, and short adsorption equilibrium time. Moreover, the adsorption mechanism is investigated by Fourier transform infrared spectroscopy (FT-IR) and X-ray photoelectron spectroscopy (XPS), and the results prove that the adsorption mechanism is chemical complexation. This work not only contributes to the advancement of hydrogel-based adsorbents, but also holds significant industrial potential for addressing water pollution issues and promoting sustainable development.
研究领域:
环境科学
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材料科学
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生物化学
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DOI
PubMed
高影响因子
DALTON TRANSACTIONS
·
2019
·Vol. 48
·期 15
·5035-5047
·
IF 4.052
Ling Zhu,Yue-Ling Bai,Yongmei Zhao,Feifei Xing,Ming-Xing Li,Shourong Zhu
A complexone analog chemosensor, H2L, bearing chelating bis(2-pyridylmethyl) amine and alizarin groups was synthesized via the Mannich reaction. H2L chromically responds to OH−, F−, CH3COO−, and H2PO4− in DMF, CH3CN, and acetone, but not in CH3OH or H2O. The addition of F− ions to H2L selectively induces a significant and visible color change in acetonitrile and shifts both methylene proton signals upfield. H2L also exhibits visible responses to Mg2+, Sr2+, Ba2+, Tb3+, Cu2+, Co2+, Ni2+, Zn2+, Mn2+, Cd2+, and Fe3+ in solution. AlCl3 can form an Al : L = 2 : 3 complex that not only changes the color of the DMF solution, but also significantly increases its fluorescence intensity. The limit of fluorescence turn-on detection for AlCl3 in DMF is 2.7 × 10−8 M, which is an order higher than those of other anthraquinone sensors reported in the literature. NMR spectroscopy shows that hydroxyl is not deprotonated upon interacting with Al3+, but will be partially deprotonated in the presence of Zn2+. Contrary to the complexone, the H2L–Ce(III) complex does not react chromically to F−. However, the H2L–NiCl2 complex responds chromically to F−, with higher sensitivity (LOD = 1.3 × 10−6 M F− in acetonitrile) than free H2L. The spectral changes in the presence of F− are similar to that of OH−; however, the spectrum shifts slightly to a longer wavelength and is more sensitive to both H2L and the H2L–NiCl2 complex. Moreover, 4% or less H2O in the solvent essentially has no influence on the F− sensitivity; however, high water content significantly decreases the F− sensitivity. The spectral changes of the Zn2+, Cu2+, Fe3+, Ce3+, and Ni2+ complexes in the presence of different NaOH concentrations were also investigated.
研究领域:
化学传感器
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分析化学
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配位化学
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DOI
PubMed
高影响因子
Materials Science & Engineering C-Materials for Biological Applications
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2017
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IF 4.164
Ruming Jiang,Han Liu,Meiying Liu,Jianwen Tian,Qiang Huang,Hongye Huang,Yuanqing Wen,Qian-yong Cao,Xiaoyong Zhang,Yen Wei
Multicomponent reactions (MCRs) have recently attracted great attention as one of the most important tools for the construction of various organic compounds in modern organic chemistry. In this work, we introduced an efficient one-pot strategy to successfully fabricate the fluorescent polymeric nanoparticles (FPNs) with aggregation-induced emission (AIE) characteristic via the conjugation of hyperbranched polyamino compound polyethyleneimine (PEI), AIE dye (named as PhE-OH) and paraformaldehyde (PF) through a Mannich reaction. The final amphiphilies (PEI-PF-PhE) can self-assemble into micelles in aqueous solution. We demonstrated PEI-PF-PhE FPNs showed high water dispersity, intense orange-yellow fluorescence, excellent photostability, low toxicity and high cell imaging performance. As compared with other construction strategies, the one-pot Mannich reaction possesses a number of advantages, such as simplicity, atom economy, high-efficiency and multifunctional potential. Combined with the remarkable properties of the AIE-active FPNs and the one-pot Mannich reaction, we could expect that the strategy developed in this work should be a useful tool for construction of various AIE-active functional materials for biomedical applications.
研究领域:
有机化学
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生物医学材料
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细胞成像
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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）