BIOPHARMACEUTICS & DRUG DISPOSITION
·
2023
·Vol. 44
·期 2
·165-174
·
IF 2.1
Xuyi Zhan,Shaoyin Bao,Xumei Li,Shaojun Zhou,Maha Raja Dahar,Nengming Lin,Xiugui Chen,Chengshan Niu,Kaige Ji,Yusheng Wu,Kui Zeng,Zhihua Tang,Lushan Yu
Osimertinib is a highly selective third-generation irreversible inhibitor of epidermal growth factor receptor mutant, which can be utilized to treat non-small cell lung cancer. As the substrate of cytochrome P450 enzyme, it is mainly metabolized by the CYP3A enzyme in humans. Among the metabolites produced by osimertinib, AZ5104, and AZ7550, which are demethylated that is most vital. Nowadays, deuteration is a new design approach for several drugs. This popular strategy is deemed to improve the pharmacokinetic characteristics of the original drugs. Therefore, in this study the metabolism profiles of osimertinib and its deuterated compound (osimertinib-d3) in liver microsomes and human recombinant cytochrome P450 isoenzymes and the pharmacokinetics in rats and humans were compared. After deuteration, its kinetic isotope effect greatly inhibited the metabolic pathway that produces AZ5104. The plasma concentration of the key metabolite AZ5104 of osimertinib-d3 in rats and humans decreased significantly compared with that of the osimertinib. This phenomenon was consistent with the results of the metabolism studies in vitro. In addition, the in vivo results indicated that osimertinib-d3 had higher systemic exposure (AUC) and peak concentration (C max ) compared with the osimertinib in rats and human body.
研究领域:
药理学
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肿瘤学
·
生物化学
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DOI
PubMed
高影响因子
JOURNAL OF SUPERCRITICAL FLUIDS
·
2023
·
IF 3.9
Yu Dong,Qiuyang Zhao,Hui Jin,Yan Miao,Yanlong Zhang,Xuetao Wang,Liejin Guo
Hydrogen donation is the key to supercritical water upgrading of heavy oil, because it benefits light distillate production and inhibits condensation , but the mechanism is still unclear. In this work, an isotope tracing method, combined with Fourier transform infrared spectroscopy and nuclear magnetic resonance spectroscopy analyses, was used to elucidate the hydrogen donation mechanism in supercritical water upgrading of asphaltenes . In asphaltenes upgrading, it was found that the aliphatic carbon at the end of the side chain of asphaltene macromolecules could capture deuterium from supercritical heavy water via free radical reactions , and the deuteration ratio at this position was 11 %. For supercritical water upgrading of vacuum residue which is generally considered as a system of asphaltenes dissolved in maltenes, the existing maltenes enhanced hydrogen donation to asphaltenes. Further, a possible hydrogen donation pathway was proposed. This work provides an in-depth understanding of the hydrogen donation mechanism for supercritical water upgrading.
研究领域:
石油化学
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物理化学
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DOI
高影响因子
JOURNAL OF ORGANIC CHEMISTRY
·
2023
·
IF 3.6
Jianbo Tang,Junhua Kong,Hui Xu,Zhi-Jiang Jiang,Yifan She,Jianfei Bai,Bencan Tang,Jia Chen,Zhanghua Gao,Kun Gao
Silver-catalyzed deuteration of nitroaromatics has been achieved using D2O as the deuterium source. Distinct from the well-established directing group-guided hydrogen-isotope exchange, this protocol showed an interesting deuteration pattern, where considerable deuterium accumulation was observed around the aromatic rings. Controlling experiments suggested that the deuteration was initiated by a silver-promoted C–H activation. Therefore, a tentative two-stage deuteration mechanism involving aryl-silver species was proposed to explain the deuteration on meta- and para-positions.
研究领域:
有机化学
·
同位素化学
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DOI
PubMed
高影响因子
JOURNAL OF ORGANIC CHEMISTRY
·
2024
·
IF 3.3
Hui Xu,Zhi-Jiang Jiang,Yun Jia,Yuhang Su,Jian-Fei Bai,Zhanghua Gao,Jia Chen,Kun Gao
Aromatic sulfones are the prevailing scaffolds in pharmaceutical and material sciences. However, compared to their widespread application, the selective deuterium labeling of these structures is restricted due to their electron-deficient properties. This study presents two comprehensive strategies for the deuteration of aromatic sulfones. The base-promoted deuteration uses DMSO-d6 as the deuterium source, resulting in a rapid H/D exchange within 2 h. Meanwhile, a silver-catalyzed protocol offers a much milder option by using economical D2O to furnish the labeled sulfones.
研究领域:
药物化学
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材料科学
·
有机合成
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DOI
PubMed
高影响因子
ACS Omega
·
2024
·
IF 3.7
Jinfeng Zheng,Jianbo Tang,Shenhao Jin,Hao Hu,Zhi-Jiang Jiang,Jia Chen,Jian-Fei Bai,Zhanghua Gao
An efficient method has been developed for the synthesis of α-deuterated α-amino esters via hydrogen isotope exchange of α-amino esters in D2O with 2-hydroxynicotinaldehyde as a catalyst under mild conditions. This methodology exhibits a wide range of substrate scopes, remarkable functional group tolerance, and affording the desired products in good yields with excellent deuterium incorporation. Notably, the ortho-hydroxyl group and the pyridine ring of the catalyst play a crucial role in the catalytic activity, which not only stabilizes the carbon-anion intermediates but also enhances the acidity of the amino esters’ α–C–H bond.
研究领域:
有机化学
·
合成化学
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DOI
PubMed
高影响因子
Nature Communications
·
2024
·Vol. 15
·期 1
·1-10
·
IF 14.7
He Meng,Li Rui,Cheng Chuanqi,Liu Cuibo,Zhang Bin
The high Faradaic efficiency (FE) of the electrocatalytic deuteration of organics with D 2 O at a large current density is significant for deuterated electrosynthesis. However, the FE and current density are the two ends of a seesaw because of the severe D 2 evolution side reaction at nearly industrial current densities. Herein, we report a combined scenario of a nanotip-enhanced electric field and surfactant-modified interface microenvironment to enable the electrocatalytic deuteration of arylacetonitrile in D 2 O with an 80% FE at −100 mA cm −2 . The increased concentration with low activation energy of arylacetonitrile due to the large electric field along the tips and the accelerated arylacetonitrile transfer and suppressed D 2 evolution by the surfactant-created deuterophobic microenvironment contribute to breaking the trade-off between a high FE and large current density. Furthermore, the application of our strategy in other deuteration reactions with improved Faradaic efficiencies at −100 mA cm −2 rationalizes the design concept.
研究领域:
化学工程
·
电化学
·
催化科学
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DOI
PubMed
高影响因子
Energetic Materials Frontiers
·
2023
·
IF 0
Zheng-hang Luo,Jia-jun Zhou,Hao Li,Yuan-hua Xia,Liang-fei Bai,Hai-jun Yang
The deuteration of energetic materials contributes to high signal-to-noise ratios (SNRs) in neutron diffraction, thus allowing the structures of energetic materials to be effectively investigated. This study developed the synthesis methods of deuterated energetic materials through chemical synthesis or newly developed one-pot H/D exchange. Using these methods, it synthesized nine deuterated energetic materials in a concise and low-cost manner: deuterated 1,3,5-triamino-2,4,6-trinitrobenzene (TATB- d 6 , 1 ), 1,3,5,7-tetranitro-1,3,5,7-tetraazacyclooctane (HMX- d 8 , 2 ), 1,3,5-trinitro-1,3,5-triazacyclohexane (RDX- d 6 , 3 ), dihydroxylammonium 5,5′-bis(tetrazole-1-oate) (TKX-50- d 8 , 4 ), nitroguanidine (NQ- d 4 , 5 ), 1,1-diamino-2,2-dinitroethylene (FOX-7- d 4 , 6 ), 2,6-diamino-3,5-dinitropyrazine-1-oxide (LLM-105- d 4 , 7 ), trinitrotoluene (TNT- d 3 , 8 ), and 3-nitro-1,2,4-triazol-5-one (NTO- d 2 , 9 ). Furthermore, the single crystals of HMX- d 8 ( 2 ) and RDX- d 6 ( 3 ) were obtained, and the α- , β- , γ- , and δ- polymorphs of HMX- d 8 ( 2 ) were prepared accordingly. The deuterated energetic materials were characterized and analyzed using infrared spectroscopy (IR), nuclear magnetic resonance (NMR) spectroscopy, differential scanning calorimetry (DSC), thermogravimetry (TG), X-ray diffraction (XRD), and neutron diffraction. Besides, this study determined the decomposition activation energy ( E a ), pre-exponential factor (A), decomposition rate constant ( k ), and critical explosion temperature ( T b ) of TATB- d 6 ( 1 ), HMX- d 8 ( 2 ), and RDX- d 6 ( 3 ) via DSC experiments at different heating rates. The NMR and neutron diffraction data show that these deuterated energetic materials have high deuteration rates of more than 95%. The DSC and TG analyses indicate that the deuterated energetic materials exhibit slightly higher decomposition temperatures than their nondeuterated counterparts. Furthermore, neutron diffraction shows that the deuterated energetic materials feature high SNRs.
研究领域:
化学
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材料科学
·
物理学
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DOI
CHEMICAL ENGINEERING JOURNAL
·
2024
·
IF 13.3
Sheng-Hua Li,Tuo-Yu Zhou,Shu-Yue Yang,Tai-Wen Li,Penglin Zhang,Guang-Yue Li,Chang Li,Hong-Qiao Li,Jing-Yi Li,Qian Zhao
The development of large-scale manufacture for low-cost afterglow materials is critical for their applications and industrializations. Herein, we presented the organic–inorganic afterglow materials with multiple colors based on boric acid (BA) and aromatic dicarboxylic acids or their diesters. These hybrid materials were facilely prepared by a solution-processable method via evaporating the solvent of the BA and organics solution at room temperature. The crystalized BA provided a rigid surrounding for the organics via hydrogen bonds, which effectively inhibited the non-radiative decay of triplet excitons and gave efficient and persistent room temperature afterglow with the phosphorescent quantum yield up to 57.66%. The phosphorescence properties were almost unchanged when deuterated BA was used instead of BA, indicating the deuteration of the hydrogen bond would not suppress the non-radiative decay from the excited state. Furthermore, a phosphorescence resonance energy transfer process was achieved by introducing 4-[4-(Dimethylamino)styryl]-1-methylpyridinium iodide (DASPI) as the energy acceptor. These BA based system could be used as quick-writable phosphorescent inks for multifunctional applications, such as anti-counterfeiting, information storage, encryption, and even for phosphor layer of light emitting diode. These results not only strengthen the understanding of the luminescence mechanism of BA hybrid materials, but also provide a new access to organic–inorganic afterglow materials.
研究领域:
材料科学
·
光学
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产品关联
DOI
高影响因子
RAPID COMMUNICATIONS IN MASS SPECTROMETRY
·
2019
·Vol. 34
·期 7
·e8656
·
IF 2.045
Ya-wen Li,Quan Chi,Tao Feng,Huaming Xiao,Linghe Li,Xian Wang
Rationale Interactions of drug molecules and proteins play important roles in physiological and pathological processes in vivo. It is of significance to establish a reliable strategy for studying protein–drug ligand interactions and would be helpful for the design and screening of new drugs in pharmacological research. Methods The interactions between four indole alkaloids (IAs) extracted from Ophiorrhiza japonica ( O. japonica ) and myoglobin (Mb) protein were investigated using a multi-spectrometric and computational method of native electrospray ionization mass spectrometry (native ESI-MS), hydrogen/deuterium exchange mass spectrometry (HDX-MS), circular dichroism (CD) and molecular docking (MD). Results The IA-bound Mb complexes were analyzed using native ESI-MS, with the obtained protein-to-ligand stoichiometry at 1:1, 1:2 and 1:3. Binding constants were measured according to the interpretation of MS spectra. MD complemented MS measurements, probing the binding sites and modes of the four IAs to Mb. Analyses involving CD and HDX-MS demonstrated that exposure to IAs could affect the conformation of Mb by decreasing the α-helix content and made Mb more susceptible to HDX at the backbone. Conclusions A new MS-based integrated analysis method has been developed to successfully study the interactions of Mb and IAs extracted from O. japonica. The experimental and calculation results have good consistency, revealing all of the four IA molecules could bind to Mb to form 1:1, 1:2 and 1:3 Mb–IA complexes. The order of binding ability of these IAs to Mb was ophiorrhine B > compound C > ophiorrhine A > compound D. CD and HDX-MS results indicated that binding with IAs destabilizes Mb. HDX-MS analysis suggests that Mb becomes more susceptible to HDX, indicating that binding with IAs destabilizes the structure of Mb. In addition, the interaction with IAs affected the overall structure of Mb, ascribed to the decrease of α-helix content and less folding of the backbone.
研究领域:
药理学
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蛋白质组学
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生物化学
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF ORGANIC CHEMISTRY
·
2021
·
IF 4.354
Junhua Kong,Zhi-Jiang Jiang,Jiayuan Xu,Yan Li,Hong Cao,Yanan Ding,Bencan Tang,Jia Chen,Zhanghua Gao
A practical and scalable ortho-selective deuteration of aromatic aldehydes was accomplished by Pd-catalyzed hydrogen isotope exchange with deuterium oxide as an inexpensive deuterium source. The use of tert-leucine as a transient directing group facilitates the exchange, affording a wide range of ortho-deuterated aromatic aldehydes with deuterium incorporation up to 97%. The control experiments suggest that the addition of silver trifluoroacetate resists the unexpected reduction of Pd(II), while the theoretical study indicates a rapid reversible concerted metalation–deprotonation process.
研究领域:
有机化学
·
同位素化学
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产品关联
DOI
PubMed
高影响因子
Current Pharmaceutical Analysis
·
2023
·Vol. 19
·期 4
·282-288
·
IF 0.6
Zhang Hanzhi,Qin Feng,Sun Ning,Zheng Mengmeng,Luo Wenyan,Qiu Ya,Liu Hao,Zhang Xiangmin
Background: After the hydrolysis of daptomycin in deuterated hydrochloric acid, the deuterium-substituted kynurenine was found, but the structure of deuterium-substituted kynurenine has not been reported. Introduction: The deuterium-substituted kynurenines were simply synthesized
and confirmed to be tri- and tetra-substituted products by high resolution mass spectrum and NMR. In further, the deuterium-substituted kynurenines were used to determine the conformation of kynurenine to be L-type in daptomycin through conformation analysis combined with derivation and high
performance liquid chromatography-quadrupole time-of-flight mass spectrometry (HPLCQ/ TOF-MS). Methods: In the present study, a simple synthesis method was developed for deuteriumsubstituted kynurenine, and its structure was confirmed by high resolution mass spectrometry and NMR. L-kynurenine
was mixed with the deuterated hydrochloric acid and heated at 110 °C for 7 h. The hydrogen/deuterium exchange products of L-kynurenine were obtained through the hydrogen/deuterium exchange method. After the derivation of deuterium-substituted L-kynurenine by Marfey’s reagent, the
conformation of kynurenine in daptomycin was deduced by HPLC-Q/TOF-MS. Results: The deuterium-substituted kynurenines were confirmed to be tri- and tetra-substituted products by high resolution mass spectrum. Further, Hydrogen NMR spectrum indicated that the deuterium-substitution positions
were β-position on amino acid and 3’ and 5’ positions on the benzene ring. Thus, the tri-deuterium-substituted product was L-[β, 3’, 5’-2H3] kynurenine-d3, while the tetra-deuterium-substituted product was L-[β, β, 3’,
5’-2H4] kynurenine-d4. Furthermore, the deuterium-substituted kynurenines were used to determine the conformation of kynurenine to be L-type in daptomycin through conformation analysis combined with derivation and HPLC-Q/TOF-MS. Conclusion: The synthesis, structures,
and application of tri- or tetra- deuterium-substituted kynurenine were reported in this study.
研究领域:
生物化学
·
药物化学
·
分析化学
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DOI
高影响因子
FUEL
·
2025
·
IF 7.5
Fange Kong,Ying Zhang,Yilin Liu,Yahe Zhang,Quan Shi,Linzhou Zhang
Different oxygen species exhibit distinct reactivities and properties in fossil fuels such as petroleum and coal liquid products. Elucidating the structural characteristics of these oxygen-containing compounds is essential for effective process design and optimal feedstock selection. The presented study introduces a method combining hydrogen/deuterium exchange (HDX) with high-resolution mass spectrometry to analyze the molecular composition and functional group types of oxygen-containing compounds. Utilizing perdeuterated methanol and toluene as the solvent, we achieved an average HDX depths exceeding 95% across model compounds. The high degree of HDX allows for the inference of oxygen functional groups based on the number of incorporated deuterium atoms. Application to representative fossil fuels (coal tar, coal liquefaction oil, and crude oil) revealed substantial differences oxygen speciation both between different oils and within individual oils. The HDX provided enhanced structural insights into oxygen-containing compounds in coal-derived liquids. Specifically, phenols in coal tar were found to predominantly contain 1–4 hydroxyl groups, with higher-order hydroxylation being negligible. Oxygenated derivatives with dibenzo-α-pyrone core structures were detected as characteristic components in coal-derived products. In contrast, the predominant dioxygenated species in crude oil were carboxylic acids. Furthermore, HDX analysis elucidated the removal selectivity of oxygen functional groups during hydrotreating of coal liquefaction oil.
研究领域:
分析化学
·
能源科学
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产品关联
DOI
高影响因子
危险品化学品经营许可证（带存储）