【电子化学品检测专题】

气态分子污染物(AMCs)中酸性污染物和金属污染物分析技术进展

蔡灵喜，许竞早^*，彭振磊，张育红

（中石化（上海）石油化工研究院有限公司，上海  201208）

摘要： 随着半导体制造工艺的发展，气态分子污染物（AMCs）对芯片良率和可靠性的影响日益显著。气态分子污染物包括酸性污染物（MA）、碱性污染物（MB）、可凝结物（MC）、拆杂物（MD）、金属污染物（MM），其中酸性污染物和金属污染物是AMCs中极为重要的两类污染物。依据酸性污染物和金属污染物的主要来源及影响机制，伴随着多种采样及前处理技术技术的开发，包括冲击瓶吸收法、吸附管采样、液相萃取法、气相分解法、容器采样和在线采样等，采样后通过先进的分析技术检测含量：酸性污染物主要以离子色谱法（IC）为主，辅以化学发光法、紫外荧光法、离子迁移谱法及光腔衰荡光谱法（CRDS）等，金属污染物以电感耦合等离子体发射光谱与质谱（ICP-OES/ICP-MS）为主，同时有一些探索性的方法如全反射X射线荧光光谱法（TXRF）。根据目前面临的挑战，未来研究需聚焦高灵敏度实时监测、新型前处理方法开发及智能化污染溯源，以应对先进制程的带来的洁净度挑战，为半导体制造的可持续发展提供技术支撑。

关键词：气态分子污染物；酸性污染物；金属污染物； 半导体制造；离子色谱法；电感耦合等离子体发射光谱与质谱（ICP-OES/ICP-MS）

中图分类号：O65             文献标识码：A             文章编号：0258-3283（2025）

DOI：10.13822/j.cnki.hxsj.2025.0155

Progress in the Analysis of Acidic and Metallic Pollutants in Airborne Molecular Contaminants (AMCs)  CAI Ling-xi, XU Jing-zao^*, PENG Zhen-lei, ZHANG Yu-hong (Sinopec (Shanghai) Research Institute of Petrochemical Technology Co.,Ltd., Shanghai 201208，China)

Abstract：With the advancement of semiconductor manufacturing processes, airborne molecular contaminants (AMCs) have emerged as critical factors affecting chip yield and reliability. AMCs include acidic contaminants (MA), alkaline contaminants (MB), condensable compounds (MC), dopants (MD), and metallic contaminants (MM), among which acidic and metallic contaminants are particularly significant. Based on their primary sources and impact mechanisms of acidic and metallic contaminants, various sampling and pretreatment techniques have been developed, including impinger absorption, adsorbent tube sampling, liquid-phase extraction, vapor phase decomposition (VPD), container sampling, and online sampling. After sampling, advanced analytical techniques are employed for detection: acidic species are primarily analyzed using ion chromatography (IC), supplemented by methods such as chemiluminescence, ultraviolet fluorescence, ion mobility spectrometry (IMS), and cavity ring-down spectroscopy (CRDS). Metallic contaminants are mainly detected via inductively coupled plasma optical emission spectrometry and mass spectrometry (ICP-OES/ICP-MS), along with exploratory methods such as total reflection X-ray fluorescence spectroscopy (TXRF). To address current challenges in AMC detection, future research should focus on the development of high-sensitivity real-time monitoring, novel pretreatment strategies, and intelligent contamination source tracing system. These efforts aim to meet the increasingly stringent cleanliness requirements of advanced semiconductor process nodes and to support for the sustainable development of semiconductor manufacturing.

Key words：airborne molecular contaminants; acidic pollutants; metallic pollutants; semiconductor manufacturing; IC; Inductively Coupled Plasma Optical Emission Spectrometry and Mass Spectrometry (ICP-OES/ICP-MS)

半导体硅片表面金属污染物分析技术研究进展

常燕¹，史泽远²，郝萍¹，高一鸣¹，王勇¹，李更银^1,3，李春华^*1

(1. 上海计量测试技术研究院，上海  201203；2. 中国电子技术标准化研究院，北京  100007；

3. 上海第二工业大学 能源与材料学院，上海，201209）

摘要:随着半导体技术向5 nm及以下节点发展，硅片表面金属杂质污染已成为制约芯片性能和良率的关键因素。系统综述了硅片表面金属污染物分析技术的研究进展与应用策略，介绍了金属杂质污染的基本特性及其对器件性能的影响，以及主要的分析标准体系。重点阐述了气相分解-电感耦合等离子体质谱法、全反射X射线荧光分析、二次离子质谱法、飞行时间二次离子质谱法、俄歇电子光谱法和X射线光电子能谱法等主要技术的原理特点与应用范围，系统对比了各技术在检测限、空间分辨率、元素覆盖与化学状态表征等方面的性能差异。在此基础上，构建了基于污染物特性、分析目的和资源条件的技术选择决策框架，提出了多技术互补分析体系的优化策略，并针对工艺监控、失效分析和研发优化等不同场景设计了系统化的技术组合方案。展望未来，分析技术将向更高灵敏度、更高空间分辨率和更好的实时监测能力方向发展，为先进工艺节点的污染控制提供更有力的技术支持。

关键词: 硅片；表面金属污染物；气相分解-电感耦合等离子体质谱法；全反射X射线荧光分析；二次离子质谱法；俄歇电子光谱法；X射线光电子能谱法

中图分类号：O657               文献标识码：A             文章编号：0258-3283（2025）

DOI：10.13822/j.cnki.hxsj.2025.0116

Advances in Analytical Techniques for Metal Contamination on Semiconductor Silicon Wafer Surfaces  CHANG Yan¹, SHI Ze-yuan², HAO Ping¹, Gao Yi-ming¹, WANG Yong¹, LI Geng-yin^1,3, LI Chun-hua*¹(1. Shanghai Institute of Metrology and Testing Technology, Shanghai 2012031,China; 2. China Electronics Standardization Institute, Beijing 100007,China; 3. School of Energy and Materials,Shanghai Polytechnic University, Shanghai 201209,China)

Abstract:As semiconductor technology advances toward the 5nm node and beyond, metal contamination on silicon wafer surfaces has become a critical factor limiting chip performance and yield. This paper systematically reviews recent advances in analytical techniques and application strategies for metal impurities on silicon wafer surfaces. It begins with an introduction to the fundamental characteristics of metal contamination, its impact on device performance, and the primary analytical standard systems. The paper focuses on describing the principles, features, and application scopes of major techniques, including Vapor Phase Decomposition-Inductively Coupled Plasma Mass Spectrometry, Total Reflection X-ray Fluorescence, Secondary Ion Mass Spectrometry, Time-of-Flight Secondary Ion Mass Spectrometry, Auger Electron Spectroscopy, and X-ray Photoelectron Spectroscopy. The performance of these techniques is systematically compared in terms of detection limits, spatial resolution, elemental coverage, and chemical state characterization. Based on these insights, a decision-making framework for selecting appropriate analytical methods is proposed, considering contamination characteristics, analytical objectives, and resource conditions. Optimization strategies for integrated, multi-technique analysis systems are presented, along withtailored technical solutions for specific scenarios such as process monitoring, failure analysis, and research and development optimization. Looking ahead, analytical techniques are expected to evolve toward higher sensitivity, better spatial resolution, and improved real-time monitoring capabilities, providing stronger technical support for contamination control in advanced process nodes.

Keywords: silicon wafer; surface metal contamination; vapor phase decomposition-inductively coupled plasma mass spectrometry; total reflection X-ray fluorescence; secondary ion mass spectrometry; auger electron spectroscopy; X-ray photoelectron spectroscopy

电子化学品标准化现状及展望

全灿

(中国计量科学研究院，北京  100029）

摘要：电子化学品是半导体、显示面板、光伏等电子工业的核心配套材料，被誉为芯片产业的“生长激素”，广泛应用于晶圆清洗、蚀刻、光刻、沉积等关键制程。电子化学品主要包括超净高纯试剂、光刻胶配套溶剂、特种气体等卡脖子材料，其纯度和杂质含量直接影响芯片产品性能。我国高度重视电子化学品的国产化生产，标准化是支撑我国半导体产业自主发展的关键技术支撑。首次系统分析了多晶硅、智能手机柔性电子材料等电子化学品在芯片制作过程中的应用及市场布局；研究了国际半导体产业协会（SEMI）代表性电子级溶剂、酸、碱以及电子特气等代表性电子化学品的标准化概况以及我国电子化学品领域的相关政策以及标准化现状；总结了我国电子级溶剂纯度和痕量杂质领域相关标准物质研制及其量值溯源技术研究概况，包括系列高纯溶剂标准物质、高纯硅标准物质和超高纯氦气纯度标准物质等为构建自主可控的半导体材料供应链提供了关键技术支撑。研究成果对推进电子化学品国产化进程、保障我国半导体产业安全、服务国家高质量发展战略具有重要参考价值，尤其为破解我国高端电子化学品"生产工艺-产品标准-量值溯源"提供了系统性支撑。

关键词：电子化学品；标准化；标准物质；半导体材料供应链

中图分类号：TQ42/O6              文献标识码：A             文章编号：0258-3283（2025）

DOI：10.13822/j.cnki.hxsj.2025.0071

The current status and prospects of standardization of electronic grade chemicals

QUAN Can (National Institute of Metrology, Beijing 100029,China)

Abstract：Electronic chemicals serve as the core supporting materials for the electronics industry, including semiconductors, display panels, and photovoltaics, and are hailed as the "growth hormone" of the chip industry. They are widely used in key manufacturing processes such as wafer cleaning, etching, photolithography, and deposition. These critical materials, including ultra-pure reagents, photoresist solvents, and specialty gases, directly impact chip performance due to their purity and impurity levels. China places great emphasis on the domestic production of electronic chemicals, with standardization being a key technological foundation for the independent development of the semiconductor industry. A systematic analysis was conducted on the applications and market landscape of electronic chemicals, such as polysilicon and flexible electronic materials for smartphones, in chip manufacturing. The standardization frameworks of representative electronic-grade solvents, acids, alkalis, and specialty gases under the International Semiconductor Industry Association (SEMI) were investigated, along with China's relevant policies and standardization progress in this field. Key achievements in reference material development and metrological traceability for electronic-grade solvents and trace impurities were summarized, including high-purity solvent reference materials, high-purity silicon reference materials, and ultra-high-purity helium gas standards, providing critical technical support for establishing a self-sufficient semiconductor material supply chain. The findings offer significant insights for advancing the domestic production of electronic chemicals, ensuring the security of China's semiconductor industry, and supporting the national high-quality development strategy. Particularly, they provide a systematic solution to overcoming challenges in "production processes-product standards-metrological traceability" for high-end electronic chemicals..

Key words: electronic grade chemical; Standardization; certified reference materials; semiconductor materials supply chain

电子化学品前驱体材料中金属杂质分析技术研究进展

李更银^{1, 2}，史泽远³，李春华¹，许剑光²，张星宇²，王俊²，常燕^*1

(1. 上海计量测试技术研究院，上海  201203; 2. 上海第二工业大学 能源与材料学院，上海  201209；3. 中国电子技术标准化研究院，北京  100007)

摘要：随着半导体制程特征尺寸缩小至纳米级，前驱体材料中金属杂质控制已成为影响器件性能和良率的决定性因素。阐述了电子化学品前驱体的定义、分类及标准体系现状。系统梳理了固态、液态和气态前驱体的样品前处理技术，针对不同形态前驱体的特殊性质和分析需求，深入分析了电热板湿法消解、微波消解、灰化法、热挥发-酸溶解法、酸雾消解法、石墨熏蒸法、直接酸消解法、减压蒸馏法、溶液吸收法、气体吸收-水解混合法等关键技术的原理、适用条件和技术要点。论述了电感耦合等离子体质谱（ICP-MS）技术在前驱体分析中面临的质谱干扰和基体效应问题，以及高分辨率质谱、反应/碰撞池技术等解决方案。在分析方法验证与质量保证方面，针对前驱体材料缺乏标准参考物质、基体复杂多变、检测限要求极低等挑战，提出结合测量系统分析（MSA）与传统验证方法的综合策略，通过系统评估重复性、再现性和关键变异因素，确保方法的可靠性。随着半导体工艺迈入5 nm及以下节点，前驱体材料金属杂质分析将向前处理与仪器分析技术融合、人工智能应用、在线监测等方向发展。加强方法标准和标准物质研制，建立完善的质量控制体系，对支撑电子化学品前驱体材料产业发展具有重要意义。

关键词：电子化学品前驱体；金属杂质分析；样品前处理；电感耦合等离子体质谱；质谱干扰；基体效应；方法验证

中图分类号：O65             文献标识码：A           文章编号：0258-3283（2025）

DOI：10.13822/j.cnki.hxsj.2025.0118

Research Progress on Analysis Technology of Metal Impurities in Electronic Chemical Precursor Materials  LI Geng-yin^1,2, SHI Ze-yuan³, LI Chun-hua¹, XU Jian-guang², ZHANG Xing-yu², WANG Jun²,CHANG Yan^*1 (1. Shanghai Institute of Metrology and Testing Technology, Shanghai 201203, China; 2. School of Energy and Materials, Shanghai Polytechnic University, Shanghai 201209, China; 3. China Electronics Standardization Institute, Beijing 100007, China)

Abstract: As semiconductor manufacturing processes advance to the nanometer level, the control of metal impurities in precursor materials has become a critical factor affecting device performance and yield. This article first outlines on the definition, classification, and current status of the standard system of electronic chemical precursors. It then systematically reviews sample pretreatment techniques for solid, liquid, and gaseous precursors. In view of the unique properties and analytical requirements of different precursors forms, the principles, applicable conditions, and technical key points of various methods including wet digestion with electric heating plates, microwave digestion, ashing, thermal volatilization - acid dissolution, acid mist digestion, graphite fumigation, direct acid digestion, vacuum distillation, solution absorption and gas absorption - hydrolysis mixing were discussed in depth. The article further discusses the challenges in inductively coupled plasma mass spectrometry (ICP-MS) for precursor analysis, including spectral interference and matrix effect, and presents solutions such as high-resolution mass spectrometry and reaction/collision cell technology. In terms of analytical method validation and quality assurance, challenges such as the lack of standard reference materials for precursor materials, complex and variable matrices, and extremely low detection requirements are addressed by proposing a comprehensive strategy combining Measurement System Analysis (MSA) and traditional validation methods. By systematically evaluating repeatability, reproducibility, and key variation factors, the reliability of the method is ensured. As semiconductor nodes move into the 5 nm and sub-5 nm era, the analysis of metal impurities in precursor materials is expected to evolve towards integrated pretreatment and analytical technologies, artificial intelligence applications, and real-time online monitoring. Strengthening the research and development of method standards and reference materials and establishing a complete quality control system are of great significance for supporting the development of the electronic chemical precursor materials industry.

Key words: electronic chemical precursors; metallic impurity analysis; sample pretreatment; inductively coupled plasma mass spectrometry; mass spectrometric interference; matrix effect; method validation

电子级无机酸中痕量阴阳离子检测技术进展

王勇，常燕，郝萍，李春华，曹建雄，高一鸣^*

（上海市计量测试技术研究院，上海 201203）

摘要: 集成电路产业的迅猛发展推动着全球半导体行业向高端制程迈进，湿电子化学品中无机酸作为集成电路产业的关键材料，其纯度直接影响芯片制造的工艺稳定性和产品良率。相应地，电子级无机酸中阴阳离子杂质检测技术的发展显得尤为重要。离子色谱法因其检测灵敏度高，快速方便和结果准确等优点，广泛应用于湿电子化学品电子级无机酸中痕量阴离子的检测，同样地，电感耦合等离子体质谱法因其抗干扰能力强，动态范围宽和快速准确分析等优点，广泛应用于湿电子化学品电子级无机酸中痕量阳离子的检测。简要介绍了电子级无机酸中硝酸、氢氟酸、盐酸、硫酸和磷酸的理化性质和在半导体工艺中的作用，并将国内外标准中的关键指标进行了列表对比，对近年来电子级无机酸中阴阳离子检测技术的研究进展进行了综述，重点介绍了各种无机酸在进行阴离子和阳离子检测时样品的前处理方法，容易遇到的检测难点以及相应地解决方法。此外，还探讨了湿电子化学品在半导体行业的未来发展趋势。

关键词：湿电子化学品；无机酸；阴阳离子；国内外标准；技术进展

中图分类号：O657.63         文献标识码：A         文章编号：0258-3283（2025）

DOI：10.13822/j.cnki.hxsj.2025.0120

Progress in the Detection Technology of Trace Anions and Cations in Electronic Grade Inorganic Acids  WANG Yong, CHANG Yan , HAO Ping, LI Chun-hua, CAO Jian-xiong, GAO Yi-ming^* (Shanghai Institute of Measurement and Testing Technology, Shanghai 201203, China) 

Abstract：The rapid development of the integrated circuit industry is propelling the global semiconductor sector toward advanced manufacturing processes. Inorganic acids, as critical components of wet electronic chemicals, are key materials for the integrated circuit fabrication, where their purity directly impacts the process stability and product yield. Accordingly, the development of detection technologies for anions and cations impurities in electronic-grade inorganic acids has become particularly important. Ion chromatography is widely used for the detection of trace anions in electronic-grade inorganic acids due to its high detection sensitivity, rapidity, convenience and accuracy. Likewise, inductively coupled plasma mass spectrometry is extensively used for the trace cations detection due to its strong anti-interference ability, wide dynamic range, and rapid, accurate analysis. This review briefly introduces the physicochemical properties and roles of five commonly used electronic-grade inorganic acids―nitric acid, hydrofluoric acid, hydrochloric acid, sulfuric acid and phosphoric acid―in electronic-grade inorganic acids. Key indicators from domestic and international standards are compared and summarized. The recent progress of anion and cation detection technology in electronic-grade inorganic acids was comprehensively reviewed with a focus on sample pretreatment methods for various inorganic acids during anion and cation detection, common analytical challenges, and the corresponding solutions. In addition, the future development trends of wet electronic chemicals in the semiconductor industry are also discussed.

Key words：wet electronic chemicals; inorganic acid; anion and cation; domestic and international standards; technical progress

三重四极杆质谱技术在电子化学品中痕量元素检测应用进展

曾远^*,2，贺兆波²，杨磊²，雷雯³，吴昊^*1,2，池汝安¹，李少平^1,2

（1. 湖北三峡实验室，湖北 宜昌  443007；2. 湖北兴福电子材料股份有限公司，湖北 宜昌  443007；3.湖北工业大学，湖北 武汉  430068）

摘要：半导体工艺与技术的飞速发展促使集成电路制造的器件尺寸不断缩小，对环境及原材料污染控制的要求愈发严格。随着半导体制造技术迈向纳米级，电子化学品的纯度要求持续提升，检测杂质水平也从微克/升（μg/L）降至皮克/升（pg/L）级别。在半导体器件制造中，痕量杂质元素及污染控制是关键环节，这些杂质可能来源于晶圆基板或电子化学品试剂，尤其是金属离子和纳米颗粒，会对器件性能和产量产生负面影响。因此，制造工厂需采用高纯度化学试剂并严格控制杂质污染。电感耦合等离子体质谱（ICP-MS）凭借其高灵敏度、多元素同时检测能力以及对复杂基质的良好耐受性，已成为高纯电子化学品杂质检测的首选技术之一。近年来，ICP-MS技术不断创新，特别是三重四极杆串联ICP-MS（ICP-QQQ）的出现，进一步提升了检测性能，尤其适用于超高纯电子化学品的检测。总结了ICP-QQQ在关键电子化学品检测痕量杂质元素方面的优势与挑战，详细论述其在酸性化学品、有机化学品中金属/非金属杂质检测的研究进展，特别针对高纯有机化学品及实验室本底控制等方法条件进行了深入探讨。最后，对ICP-QQQ技术的发展趋势进行了展望，并提出了未来研究方向，以期为相关领域研究提供参考。

关键词：半导体工业；硅基材料；电子化学品；痕量杂质元素；三重四极杆串联电感耦合等离子体质谱

中图分类号：O65               文献标识码：A                  文章编号：0258-3283（2025）

DOI：10.13822/j.cnki.hxsj.2025.0100

Advances in the Application of Triple Quadrupole Mass Spectrometry for Ultratrace Element Detection in Electronic Chemicals  ZENG Yuan^*1,2, HE Zhao-bo², YANG Lei², Lei Wen³, WU Hao^*1,2 , CHI Ru-an¹, LI Shao-ping^1,2（1. Hubei Three Gorges Laboratory, Yichang 443007, China; 2. Hubei Sinophorus Electronic Materials Co., Ltd., Yichang 443007, China; 3. HuBei University of Technology, Wuhan 430068, China）

Abstract: The rapid advancement of semiconductor processes and technologies has led to the continuous miniaturization of integrated circuit (IC) devices and increasingly stringent requirements for environmental and raw material pollution control. As semiconductor manufacturing technology progresses to the nanoscale, the purity requirements for electronic chemicals have increased, with the detection of impurity levels decreasing from micrograms per liter (μg/L) to picograms per liter (pg/L). In semiconductor device manufacturing, controlling trace impurity elements and contamination is crucial. These impurities, which may originate from the wafer substrates or electronic chemical reagents, particularly metal ions and nanoparticles, can negatively impact device performance and yield. Therefore, semiconductor manufacturing plants must use high-purity chemical reagents and rigorously control impurity contamination. Inductively coupled plasma mass spectrometry (ICP-MS) has become one of the preferred techniques for detecting impurities in high-purity electronic chemicals due to its high sensitivity, capability for simultaneous multi-element detection, and strong tolerance for complex matrices. In recent years, ICP-MS technology has been continuously innovated, especially with the advent of triple quadrupole ICP-MS (ICP-QQQ), which has further enhanced detection performance and is particularly suitable for the detection of ultra-high-purity electronic chemicals. This article reviews the advantages and challenges of ICP-QQQ in detecting trace impurity elements in key electronic chemicals and provides a detailed discussion on the research progress of metal/non-metal impurity detection in acidic and organic chemicals. Special attention is given to the methodological conditions for high-purity organic chemicals and laboratory background control. Finally, the future trends of ICP-QQQ technology are discussed, and potential research directions are proposed to serve as a reference for related studies in the field.

Key words: semiconductor; silicon materials; electronic chemicals; ultratrace impurity elements; triple quadrupole ICP-MS

超净高纯试剂中微量有机杂质和水分的脱除进展

秦磊^*，陈亮

（中石化（上海）石油化工研究院有限公司绿色化工与工业催化全国重点实验室，上海  201208）

摘要：超净高纯试剂是集成电路、新型显示、印刷电路板等行业中不可或缺的重要关键化工材料。随着全球人工智能、物联网、5G产业的迅速发展，带动了国内集成电路等相关产业的发展，对超净高纯试剂的需求将进一步显著增加。超净高纯试剂除对金属离子和颗粒物有严格管控外，对产品中的有机杂质和水分残留按照产品等级或者应用领域不同也有着非常苛刻的要求。超净高纯试剂中微量有机杂质和水分的存在会极大影响产品的使用效果，甚至会降低晶圆的良率。极低的有机杂质和水分脱除是超净高纯试剂纯化技术的关键点，也是其制备的技术难点，特别是需要同步保证纯化后产品的高纯度和较高的回收率。虽然近几年国内超净高纯试剂产业发展迅速，但是纯化手段与国外先进企业还略有差距。为此，针对目前超净高纯试剂中的微量有机杂质和水分脱除方法进行了简要综述，特别对精馏法、吸附法、结晶法、膜分离法以及反应法的脱除技术原理以及应用情况展开了介绍，并结合集成电路产业未来发展方向，对超净高纯试剂纯化技术提出了建议和展望。

关键词：超净高纯试剂；有机杂质；水分；微量；分离方法

中图分类号：O69             文献标识码：A            文章编号：0258-3283（2025）

DOI：10.13822/j.cnki.hxsj.2025.0122

Progress in the Removal of Trace Organic Impurities and Moisture from Ultra-clean and High-purity Reagents  QIN Lei*, CHEN Liang (State Key Laboratory of Green Chemical Engineering and Industrial Catalysis, SINOPEC (Shanghai) Research Institute of Petrochemical Technology Co., Ltd., Shanghai 201208, China)

Abstract：Ultra-clean and high-purity reagents are essential materials in key industries such as integrated circuits, new display, and printed circuit boards. With the rapid global development of artificial intelligence, the Internet of Things, and 5G technologies, the growth of domestic industries, particularly integrated circuit, has significantly increased the demand for such reagents. In addition to stringent control over metal ions and particles, ultra-clean and high-purity reagents must also meet rigorous standards regarding organic impurities and residual moisture, depending on the product grades or application fields. The presence of trace amounts of organic impurities and moisture can severely affect the performance and reduce wafer yield. The efficient removal of these ultra-trace contaminants is both a critical aspect and a major technical challenge in purification process, especially when high purity must be maintained alongside high product recovery. Although China’s ultra-clean high-purity reagent industry has advanced rapidly in recent years, its purification techniques still slightly lag behind those employed by leading international manufacturers. This review provides a concise review of the current methods for removing trace organic impurities and moisture in ultra-clean and high-purity reagents. It highlights the principles and practical applications of distillation, adsorption, crystallization, membrane separation, and reactive purification methods. Combined with the future development trends of the integrated circuit industry, recommendations and prospects for ultra-clean and high-purity reagent purification technology are proposed. 

Key words：ultra-clean and high-purity reagents; organic impurities; moisture; trace; separation method

【生化与药用试剂】

聚β-氨基酯基因载体改性研究进展

张博¹，袁梓诺¹，陈绮琪¹，曾明²，李湘¹，熊梧琬^*1

（1. 肇庆学院 环境与化学工程学院，广东 肇庆  526061；2. 中山大学附属第六医院皮肤科，广东广州  510655）

摘要：在基因治疗领域中，如何设计并制备出一种相容性好、转染效率高和细胞毒性低的基因载体，并将其应用于基因传递过程一直是人们研究的热点。当前，基因载体主要分为病毒类和非病毒类两大类型。在临床治疗中，病毒类载体的转染效率较高，但由于其存在整体安全性较低、制备工艺复杂和易引发免疫应答反应等缺点，大大限制了其在基因治疗中的应用。非病毒类载体聚β-氨基酯（PBAEs），是利用迈克尔加成反应机理，由胺和丙烯酸酯类单体合成的一种聚合物，具备高细胞活性、低细胞毒性、原料易得、合成简单以及结构多样等优点，是一类有广阔应用前景的非病毒基因载体材料。近年来，随着聚β-氨基酯研究的深入，众多的改进方法被应用于对其结构的改性优化，从而使其性能得到了持续的提升。主要从枝化、封端、侧链修饰、末端修饰以及嵌段修饰5个方面对聚β-氨基酯的改性研究进展进行了综述，并且对聚β-氨基酯的工业化生产和质量控制进行了讨论，为基因治疗领域的研究提供参考。

关键词：聚β-氨基酯；阳离子聚合物；基因载体；改性；转染效率

中图分类号：O631         文献标识码：A              文章编号：0258-3283（2025）

DOI：10.13822/j.cnki.hxsj.2025.0085

Research Progress on Modification of Poly (β-amino ester) Gene Vector  ZHANG Bo¹, Yuan Zi-nuo¹, CHEN Qi-qi¹, ZENG Ming², LI Xiang¹, XIONG Wu-wan^1*(1. College of Environmental and Chemical Engineering, Zhaoqing University, Zhaoqing 526061, China; 2. Department of Dermatology, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou 510655, China)

Abstract： The design and development of gene carriers with excellent biocompatibility, high transfection efficiency, and low cytotoxicity, as well as their application in gene delivery, remain key research focuses in gene therapy. Currently, gene vectors are mainly divided into viral and non-viral types. Viral vectors offer high transfection efficiency in clinical applications; however, their application is significantly limited by safety concerns, complex manufacturing processes, and the risk of eliciting immune responses. Poly(β-amino esters) (PBAEs) are a class of non-viral vectors synthesized via the Michael addition between amine and acrylate monomers. They offer advantages such as high cellular activity, low cytotoxicity, readily available raw materials, straightforward synthesis, and structural diversity, positioning them as promising candidates for non-viral gene delivery. In recent years, research on PBAEs has advanced, with numerous modification strategies applied to optimize their structures and improve their performance. This review summarizes progress in five major modification approaches: branching, capping, side chain modification, end-group modification, and block copolymerization. Furthermore, industrial-scale production and quality control of PBAEs are discussed. This review aims to provide valuable insights and references for research within the gene therapy domain.

Key words：poly(β-amino esters); cationic polymer; gene vectors; modification; transfection efficiency

【功能材料】

淀粉微胶囊改性镁铁铜三元水滑石及其对聚氯乙烯材料性能的影响

张恒^a，王佳悦^a，蓝心杏^a，罗肖^a,b，马维勋^a,b，赵良莲^a,c，朵兴红^*a,b,c

(青海民族大学 a.化学与材料科学学院；b. 青藏高原资源化学与生态环境保护国家民委重点实验室；c. 青海省应用物理化学重点实验室，青海西宁  810007）

摘要：水滑石类化合物（LDHs）作为一种无卤、无害且高效的无机阻燃剂，具有消烟、阻燃等多种功能，在阻燃领域极具开发潜力。但水滑石粒子易团聚，在聚合物基体中分散性差进而影响材料机械性能。为解决这一问题，采用马铃薯淀粉（PS）对MgFeCu-LDHs进行微胶囊包覆改性，合成了PS@MgFeCu-LDHs。利用X射线衍射（XRD）、傅里叶红外光谱（FT-IR）、透射电子显微镜（TEM）对其进行了结构性表征；随后将PS@MgFeCu-LDHs加入到聚氯乙烯（PVC）材料中，制备复合材料。并对其抑烟性能、阻燃性能、机械性能进行了测试。结果表明，PS@MgFeCu-LDHs/PVC复合材料具有良好的阻燃抑烟性能，4%PS@MgFeCu-LDHs/PVC复合材料的最大比光密度下降至14.63，相比于PVC的33.13，降幅达55.8%。由于淀粉的引入，PS@MgFeCu-LDHs能有效增加PVC的残炭率，提高热稳定性能。力学测试表明，PS@MgFeCu-LDHs在复合材料中的相容性较好。同时，极限氧指数（LOI）也提升至25.6，UL-94水平燃烧测试等级达HB级。研究结果为添加型无机阻燃剂提供了新策略，用以降低PVC材料的火灾风险。

关键词：聚氯乙烯；水滑石；微胶囊；阻燃；抑烟

中图分类号：O61        文献标识码：A             文章编号：0258-3283（2025）

DOI：10.13822/j.cnki.hxsj.2025.0093

Modification of MgFeCu-LDHs by Starch Microcapsules and Its Effect on the Properties of Polyvinyl Chloride Materials  ZHANG Heng^a, WANG Jia-yue^a, Lan Xin-xing^a, LUO Xiao^a,b, MA Wei-xun^a,b, ZHAO Liang-lian^a,c, DUO Xing-hong^*a,b,c(a.School of Chemistry and Materials Science College, b. State People's Committee Key Laboratory of Resource Chemistry and Ecological Environment Protection on the Qinghai-Tibetan Plateau, c. Qinghai Provincial Key Laboratory of Applied Physical Chemistry, Qinghai Minzu University, Xining 810007, China)

Abstract：Layered double hydroxides (LDHs), as a kind of halogen-free, non-toxic, and efficient inorganic flame retardant, possess multiple functions such as flame retardancy and smoke elimination, showing great potential for applications in fire-safe material. However, LDH particles tent to agglomerate and exhibits poorly dispersion within polymer matrix, which adversely affects the mechanical properties of the resulting composites. To address this issue, potato starch (PS) was used to microencapsulate and modify MgFeCu-LDHs, resulting in PS@MgFeCu-LDHs. The structure of the modified LDHs was characterized by X-ray diffraction (XRD), Fourier infrared spectroscopy (FT-IR), and transmission electron microscopy (TEM). The PS@MgFeCu-LDHs was then incorporated into polyvinyl chloride (PVC) materials to prepare the composite material. The smoke suppression, flame retardant, and mechanical properties were evaluated. The results showed that the PS@MgFeCu-LDHs/PVC composites exhibited excellent performance. Specifically, the maximum specific optical density of the composites containing 4%PS@MgFeCu-LDHs/PVC decreased to 14.63, representing a 55.8% reduction compared to 33.13 for pure PVC. The presence of starch enhanced the char residue rate and thermal stability of the composites. Mechanical testing further indicated good compatibility between PS@MgFeCu-LDHs and the PVC matrix. Additionally, the limiting oxygen index (LOI) increased to 25.6, and the composite achieved an HB rating in the UL-94 horizontal burning test. The results offer a promising strategy for developing additive-type inorganic flame retardants to reduce the fire risk of PVC materials.

Key words： polyvinyl chloride (PVC); layered double hydroxides (LDHs);microcapsule; flame retardant; smoke suppression

【分析与测试】

改进QuEChErs-同位素内标-UPLC-MS /MS快速测定禽蛋和鸡肉中喹诺酮类药物残留及暴露风险水平研究

陈旭¹，刘春波^*2，张海燕²，包玉兰²，张丽敏²，赵宏²

（1.内蒙古自治区中医医院，内蒙古呼和浩特  010010，2.呼和浩特市疾病预防控制中心，内蒙古呼和浩特  010010）

摘要：建立一种QuEChERS-同位素-UPLC-MS/MS方法，用于快速测定禽蛋和鸡肉中6种喹诺酮类药物的残留；根据检测数据分析内蒙古地区禽蛋和鸡肉中喹诺酮类药物的污染水平，使用喹诺酮类药物的总危害商数（ΣQ_HQ）评估膳食暴露风险。通过改进QuEChERS前处理技术（提取液、吸附净化剂）、色谱柱和流动相等条件优化实验方法，将优化后的方法应用于233份禽蛋和鸡肉样品。使用T3色谱柱、V（5 mmol/L甲酸铵和0.1%甲酸水）?V（甲醇）=98?2和V（5 mmol/L甲酸铵和0.1%甲酸水）?V（甲醇）=2?98流动相、Discovery® DSC-18 SPE作吸附剂、V（5mmol/L甲酸铵和0.1%甲酸水）?V（乙腈）=2?98为提取液，6种喹诺酮类药物色谱峰形尖锐，分离效果好，响应值高，在1~100 ng/mL范围内线性关系良好，相关系数R≥0.9990，检出限范围为0.3~1 μg/kg，定量限范围为1~3 μg/kg，在3个不同加标水平浓度点的回收率范围为88.1%~117.1%，相对标准偏差范围为0.6%~7.19%（n=6）。禽蛋中喹诺酮类药物的检出率为3.33%（4/120），鸡肉中喹诺酮类药物的检出率为6.19%（7/113），总体检出率为4.72%（11/233）。改进后的方法具有较低的检出限和较高的准确度，能够简单快速地测定禽蛋和鸡肉中的喹诺酮类药物残留。在喹诺酮类药物的风险评估中，各年龄组的6种喹诺酮类药物的Q_HQ均小于1，各年龄组的总危害商数（ΣQ_HQ）均小于1，风险处于可接受的水平。

关键词：QuEChErs；同位素；超高效液相色谱串联质谱法；喹诺酮类；膳食暴露风险

中图分类号：O657;X04     文献标识码：A              文章编号：0258-3283（2025）

DOI：10.13822/j.cnki.hxsj.2025.0109

Research on the Rapid Determination of Quinolones Residues and Exposure Risk Levels in Poultry Eggs and Chicken by Improving QuEChERS-Isotope Internal Standard-UPLC-MS/MS Method CHEN Xu¹,LIU Chun-bo^*2,ZHANG Hai-yan²,BAO Yu-lan²,ZHANG Li-min²,ZHAO Hong²（1.Inner Mongolia Autonomous Region Hospital of Traditional Chinese Medicine Hohhot 010010 China,2.Hohhot Center for Disease Control and Prevention, Hohhot 010010 China)

Abstract: A QuEChERS-isotope-UPLC-MS/MS method was developed for the rapid determination of six quinolone residues in poultry eggs and chicken meat. Based on the contamination levels of quinolones detected in poultry eggs and chicken meat in Inner Mongolia region, the dietary exposure risk was evaluated using the total hazard quotient (ΣQ_HQ) of quinolones. The method was optimized by improving the QuEChERS pre-treatment technique (extraction solution and adsorption purification agent), chromatographic column, and mobile phase membrane conditions, and was applied to 233 poultry egg and chicken meat samples. Using a T3 chromatographic column with mobile phases V (5 mmol/L ammonium formate and 0.1% formic acid in water):V (methanol)=98:2 and V(5 mmol/L ammonium formate and 0.1% formic acid in water):V(methanol) = 2:98), Discovery® DSC-18 SPE as the adsorbent, an extraction solution of V(5 mmol/L ammonium formate and 0.1% formic acid in water):V(acetonitrile)=2:98, sharp chromatographic peaks, good separation, and strong signal responses were achieved. The six quinolones showed good linearity in the range of 1 ng/mL to 100 ng/mL with correlation coefficients R≥0.9990. The detection limits ranged from 0.3 to 1 μg/kg, and the quantification limits ranged from 1 to 3 μg/kg, Recoveries at three different spiked levels ranged from 88.1% to 117.1%, and the relative standard deviations (RSDs) ranged from 0.6% to 7.19% (n = 6). The detection rate of quinolones was 3.33% (4/120) in poultry eggs and it was 6.19% (7/113) in chicken meat, with an overall detection rate of 4.72% (11/233). The improved method features low detection limits and high accuracy, enabling simple and rapid determination of quinolone residues in poultry eggs and chicken meat. Risk assessment showed that the Q_HQ for the six quinolones in all age groups was below 1, and the total hazard quotient (ΣQ_HQ) for all age groups was also less than 1, indicating an acceptable risk exposure level of dietary exposure rate.

Key words: QuEChERS; isotope; ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS); quinolones; dietary exposure risk

超高效液相色谱-质谱法测定环丙沙星中5种有关物质含量

许晓辉，李坚，吴福祥，杜锐浒，张晓萍，张生萍^*，王小乔^*

（兰州市食品药品检验检测研究院，甘肃兰州  730050）

摘要：环丙沙星中有关物质的残留水平应控制在标准规定的限度范围内，以保证其质量安全有效。建立了一种超高效液相色谱-串联三重四极杆质谱法同时测定环丙沙星中5种有关物质（杂质A、B、C、E、H）含量的分析方法。样品以乙腈超声提取，经0.22 μm有机滤膜过滤，UPLC-MS/MS检测，采用Waters ACQUITY BEH C18（2.1 mm×100 mm，1.7 μm）高性能通用性液相色谱柱分离，以水相为含0.1%甲酸-2 mmol/L乙酸铵的水溶液与有机相为含0.1%甲酸的乙腈溶液进行梯度洗脱，柱温：30℃，进样量：2 μL，流速：0.2 mL/min，采用Agilent喷射流电喷雾电离离子源，正离子下以多反应监测模式采集，外标法定量。结果显示，5种有关物质在各自范围内线性关系良好，线性相关系数R²均大于0.99，重复性的相对标准偏差≤5%，检出限和定量限分别为0.058～0.42和0.19～1.3 ng/mL，3个水平加标回收率在71.3%～118.8 %，相对标准偏差在1.0%～7.5%，6批样品中均检出有关物质，含量均符合2020年版《中国药典》限量要求。该方法前处理操作简单，准确灵敏，重复性和稳定性良好，可用于环丙沙星中有关物质的质量控制。

关键词：超高效液相色谱-质谱法；环丙沙星；有关物质；含量；测定；质量控制

中图分类号：R917，O657              文献标识码：A              文章编号：0258-3283（2025）

DOI：10.13822/j.cnki.hxsj.2025.0028

Determination of 5 Related Substances in Ciprofloxacin by Ultra High Performance Liquid Chromatography-Mass Spectrometry XU Xiao-hui, LI Jian, WU Fu-xiang, DU Rui-hu, ZHANG Xiao-ping, Zhang Sheng-ping^*, WANG Xiao-qiao^* (Lanzhou Institute for Food and Drug Control, Lanzhou 730050, Gansu, China)

Abstract: To ensure the quality, safety, and efficacy of ciprofloxacin, the residual levels of relevant substances must be controlled within the limits specified by the regulatory standards. This study developed a method for simultaneous determination of 5 related substances (impurity A, B, C, E, and H) in ciprofloxacin using ultra-high performance liquid chromatography coupled with tandem triple quadrupole mass spectrometry. The samples were extracted by ultrasonic acetonitrile, filtered through a 0.22 μm organic filter membrane, and analyzed by UPLC-MS/MS. Separation were performed by Waters ACQUITY BEH C18 column (2.1 mm×100 mm, 1.7 μm), with a mobile phase of 0.1% formic acid and 2 mmol/L ammonium of aqueous solution (aqueous phase) and 0.1% formic acid of acetonitrile (organic phase) using gradient elution. The column temperature was set at 30℃, the injection volume was 2 μL and the flow rate was 0.2 mL/min. Detection was carried out using an Agilent jet current electrospray ionization source in positive ion mode with multiple reaction monitoring mode, and quantification was performed using an external standard method. The five related substances exhibited good linearity over their respective concentration ranges, with correlation coefficients R² above 0.99. The method also showed good repeatability, with relative standard deviations (RSDs) not exceeding 5%. The detection limits and quantification were 0.058~0.42 ng/mL and 0.19~1.3 ng/mL, respectively. The spiked recoveries rates at the three spiked levels were 71.3%~118.8 %, with RSDs of 1.0%~7.5%. All six batches of samples tested positive for related substances, with contents meets the limit requirement of the 2020 edition of Chinese Pharmacopoeia. This method features simple sample preparation, high sensitivity, good repeatability and stability, and is suitable for quality control of related substances in ciprofloxacin.

Key words：Ultra high performance liquid chromatography-mass spectrometry; ciprofloxacin; related substances; content; determination; quality control

【合成与应用】

2-喹啉酮化合物的合成研究进展

罗小芹，黄桢惠，何依倩，陈清，林宁^*

（广西中医药大学 药学院 广西壮瑶药技术创新中心，广西南宁 530200）

摘要：2-喹啉酮作为含氮杂环化合物中的重要成员，因其独特的氮杂环共轭结构和多样的生物活性，在药物化学、材料科学及化学生物学等领域展现出重要的应用价值。该骨架不仅是构建复杂天然产物和功能分子的重要合成砌块，也是构成多种药物分子的核心结构单元，在抗菌（如喹诺酮类抗生素）、抗肿瘤（如蛋白激酶抑制剂）及抗炎等药物研发中具有关键作用，受到合成化学与药物化学领域的关注。随着对2-喹啉酮化合物研究的不断发展，近年其合成策略的创新成为化学研究的热点。本文综述了近年来2-喹啉酮骨架的合成研究进展，以合成其结构的反应类型为分类依据，介绍了从不同合成前体出发合成2-喹啉酮骨架的常用方法，例如光催化、过渡金属催化、电化学合成等，并对各合成方法的反应机理、底物适用性、优势和局限性进行分析，旨在为2-喹啉酮合成方法学的创新提供理论参考，同时为基于该骨架的药物设计、功能材料开发及天然产物全合成等领域的发展提供技术路线参考，助力推动相关交叉学科的前沿研究。

关键词：2-喹啉酮；药效骨架；合成；反应机理；研究进展

中图分类号：O621.3     文献标识码：A     文章编号：0258-3283（2025）

DOI：10.13822/j.cnki.hxsj.2025.0089

Research Advances in the Synthesis of 2-Quinolinones LUO Xiao-qin, HUANG Zhen-hui, HE Yi-qian, CHEN Qing, LIN Nin^* (Guangxi Innovation Center of Zhuang Yao Medicine, School of Pharmacy, Guangxi University of Chinese Medicine, Nanning 530200, China)

Abstract: 2-quinolinone, as a significant class of nitrogen-containing heterocyclic compounds, exhibit a wide range of biological activities and hold considerable value in pharmaceutical chemistry, material science, and chemical biology due to their unique nitrogen-heterocyclic conjugated structure. This scaffold not only serve as an important synthetic building block for the construction of complex natural products and functional molecules, but also represents the core structural unit that constitutes a variety of drug molecules. It playd a key role in the research and development of antibacterial (quinolone antibiotics), antitumor (protein kinase inhibitors), and anti-inflammatory drugs, attracting extensive attention in the field of synthetic chemistry and medicinal chemistry. With the continuous development of research on 2-quinolinone compounds, the innovation of its synthesis strategy has become a hot topic in chemical research in recent years. This paper reviews recent research advances in the synthesis of 2-quinolinone skeletons, classified by reaction types. Common methods for the synthesis of 2-quinolinone skeletons from different synthetic precursors were introduced, such as photocatalysis, transition metal catalysis, and electrochemical synthesis. The reaction mechanism, substrate applicability, advantages, and limitations of each synthesis method were analyzed, aiming to provide a theoretical reference for the innovation of 2-quinolinone synthesis methodology. At the same time, it provided a technical route reference for the development of drug design, functional material development and total synthesis of natural products based on the skeleton, promoting the advancement of related interdisciplinary disciplines.

Key words: 2-quinolinones; pharmacophore; synthetic strategies; reaction mechanisms; research advances

2-喹啉酮化合物的合成研究进展

罗小芹，黄桢惠，何依倩，陈清，林宁^*

（广西中医药大学 药学院 广西壮瑶药技术创新中心，广西 南宁  530200）

摘要：2-喹啉酮作为含氮杂环化合物中的重要成员，因其独特的氮杂环共轭结构和多样的生物活性，在药物化学、材料科学及化学生物学等领域展现出重要的应用价值。该骨架不仅是构建复杂天然产物和功能分子的重要合成砌块，也是构成多种药物分子的核心结构单元，在抗菌（如喹诺酮类抗生素）、抗肿瘤（如蛋白激酶抑制剂）及抗炎等药物研发中具有关键作用，受到合成化学与药物化学领域的关注。随着对2-喹啉酮化合物研究的不断发展，近年其合成策略的创新成为化学研究的热点。本文综述了近年来2-喹啉酮骨架的合成研究进展，以合成其结构的反应类型为分类依据，介绍了从不同合成前体出发合成2-喹啉酮骨架的常用方法，例如光催化、过渡金属催化、电化学合成等，并对各合成方法的反应机理、底物适用性、优势和局限性进行分析，旨在为2-喹啉酮合成方法学的创新提供理论参考，同时为基于该骨架的药物设计、功能材料开发及天然产物全合成等领域的发展提供技术路线参考，助力推动相关交叉学科的前沿研究。

关键词：2-喹啉酮；药效骨架；合成；反应机理；研究进展

中图分类号：O621.3     文献标识码：A     文章编号：0258-3283（2025）

DOI：10.13822/j.cnki.hxsj.2025.0089

Research Advances in the Synthesis of 2-Quinolinones LUO Xiao-qin, HUANG Zhen-hui, HE Yi-qian, CHEN Qing, LIN Nin^* (Guangxi Innovation Center of Zhuang Yao Medicine, School of Pharmacy, Guangxi University of Chinese Medicine, Nanning 530200, China)

Abstract: 2-quinolinone, as a significant class of nitrogen-containing heterocyclic compounds, exhibit a wide range of biological activities and hold considerable value in pharmaceutical chemistry, material science, and chemical biology due to their unique nitrogen-heterocyclic conjugated structure. This scaffold not only serve as an important synthetic building block for the construction of complex natural products and functional molecules, but also represents the core structural unit that constitutes a variety of drug molecules. It playd a key role in the research and development of antibacterial (quinolone antibiotics), antitumor (protein kinase inhibitors), and anti-inflammatory drugs, attracting extensive attention in the field of synthetic chemistry and medicinal chemistry. With the continuous development of research on 2-quinolinone compounds, the innovation of its synthesis strategy has become a hot topic in chemical research in recent years. This paper reviews recent research advances in the synthesis of 2-quinolinone skeletons, classified by reaction types. Common methods for the synthesis of 2-quinolinone skeletons from different synthetic precursors were introduced, such as photocatalysis, transition metal catalysis, and electrochemical synthesis. The reaction mechanism, substrate applicability, advantages, and limitations of each synthesis method were analyzed, aiming to provide a theoretical reference for the innovation of 2-quinolinone synthesis methodology. At the same time, it provided a technical route reference for the development of drug design, functional material development and total synthesis of natural products based on the skeleton, promoting the advancement of related interdisciplinary disciplines.

Key words: 2-quinolinones; pharmacophore; synthetic strategies; reaction mechanisms; research advances

肉桂酸衍生物的合成及其抑制α-葡萄糖苷酶活性研究

向明丽^a,b,c，曾亚玲^a,b,c，姚佳倩^a,b,c，刘文锋^*a,b,c，郭素琴^a,b,c，李红光^*a,b,c

(五邑大学a. 药学与食品工程学院，b. 华南生物医药大动物模型研究院，c. 广东省医学大动物模型重点实验室，广东 江门 529020)

摘要：肉桂酸源于肉桂皮，具有广泛的生理活性。通过酯化反应合成新型肉桂酸衍生物，并评价此类化合物对α-葡萄糖苷酶活性的影响。首先，从含不同取代基的肉桂酸原料出发，在1-(3-二甲氨基丙基)-3-乙基碳二亚胺盐酸盐（EDCI）的缩合作用下，在二甲氨基吡啶（DMAP）的催化作用下，合成新型的肉桂酸衍生物。然后，利用氢-1核磁共振（¹HNMR），碳-13核磁共振（¹³CNMR）及高分辨质谱（HR-MS）确证目标化合物的化学结构，并通过体外活性测试方法评价此类化合物对α-葡萄糖苷酶的抑制作用和作用机制。最后，通过分子对接揭示化合物的作用机制。实验结果显示，(E)-3-(4-甲基苯基)-2-丙烯酸-4-羟甲基苯酯（1a）和(E)-3-(4-甲氧基苯基)丙烯酸-4-羟甲基苯酯（1b）对α-葡萄糖苷酶具有最强的抑制活性，它们的IC₅₀值分别为（22.23± 2.21）和（38.23± 2.59）μmol/L，显著低于阿卡波糖。酶动力学研究表明，化合物1a的抑制类型为混合型，而化合物1b的抑制类型为非竞争型。分子模拟结果表明，化合物1a和1b均能嵌插在α-葡萄糖苷酶的活性口袋中，并与口袋中的氨基酸残基形成氢键。此外，化合物结构中的苯环和能与活性口袋中的疏水区域形成相互作用。因此，实验结果不仅揭示了肉桂酸衍生物作为α-葡萄糖苷酶抑制剂的构效关系，更为后续通过结构修饰进一步提高抑制活性奠定了坚实的理论基础。

关键词：肉桂酸；合成；α-葡萄糖苷酶；抑制；作用机制

中图分类号：O61    文献标识码：A             文章编号：0258-3283（2025）

DOI：10.13822/j.cnki.hxsj.2025.0096

Synthesis and Inhibitory Activity Evaluation of Novel Cinnamic Acid Derivatives against α-Glucosidase  XIANG Ming-li^a,b,c, ZENG Ya-ling^a,b,c, YAO Jia-qian^a,b,c, LIU Wen-feng^*a,b,c, GUO Su-qin^a,b,c, LI Hong-guang^*a,b,c (a. School of Pharmacy and Food Engineering, b. Wuyi University, Guangdong Provincial Key Laboratory of Large Animal Models for Biomedicine, South China Institute of Large Animal Models for Biomedicine, Jiangmen 529020, China)

Abstract：Cinnamic acid, derived from cinnamon bark, exhibits a wide range of physiological activities. Inspired by this, a series of novel cinnamic acid derivatives were synthesized via esterification, and their inhibitory effects on α-glucosidase activity were evaluated. Starting from cinnamic acid precursors with different substituents, the target derivatives were synthesized through a condensation reaction mediated by 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (EDCI) and catalyzed by 4-dimethylaminopyridine (DMAP). The chemical structures of the synthesized compounds were confirmed using ¹HNMR, ¹³CNMR, and high-resolution mass spectrometry (HR-MS). Subsequently, their inhibitory effects on α-glucosidase were assessed through in vitro assays, followed by studies on their mechanisms of action. Molecular docking was also performed to elucidate their binding interactions. The results demonstrated that compounds 1a and 1b exhibited the strongest inhibitory activity against α-glucosidase, with IC₅₀ values of (22.23 ± 2.21 )and (38.23 ± 2.59) μmol/L, respectively, which are significantly lower than that of acarbose. Enzyme kinetic studies revealed that compound 1a acted as a mixed-type inhibitor, while compound 1b displayed noncompetitive inhibition. Molecular docking indicated that both compounds bind within the active pocket of α-glucosidase, forming hydrogen bonds with the amino acid residues. Additionally, the phenyl rings of the compounds interacted with hydrophobic regions within the binding pocket. These findings not only elucidated the structure-activity relationship (SAR) of cinnamic acid derivatives as α-glucosidase inhibitors, but also provided an theoretical foundation for further structural optimization to enhance their inhibitory potency.

Key words：cinnamic acid; synthesis; α-glucosidase; inhibition; mechanism