2025年47（9）中英文摘要
【電子化學品檢測專題】
氣態分子污染物(AMCs)中酸性污染物和金屬污染物分析技術進展
蔡靈喜，許競早*，彭振磊，張育紅
（中石化（上海）石油化工研究院有限公司，上海 201208）
摘要： 隨著半導體制造工藝的發展，氣態分子污染物（AMCs）對芯片良率和可靠性的影響日益顯著。氣態分子污染物包括酸性污染物（MA）、堿性污染物（MB）、可凝結物（MC）、拆雜物（MD）、金屬污染物（MM），其中酸性污染物和金屬污染物是AMCs中極為重要的兩類污染物。依據酸性污染物和金屬污染物的主要來源及影響機制，伴隨著多種采樣及前處理技術技術的開發，包括沖擊瓶吸收法、吸附管采樣、液相萃取法、氣相分解法、容器采樣和在線采樣等，采樣后通過先進的分析技術檢測含量：酸性污染物主要以離子色譜法（IC）為主，輔以化學發光法、紫外熒光法、離子遷移譜法及光腔衰蕩光譜法（CRDS）等，金屬污染物以電感耦合等離子體發射光譜與質譜（ICP-OES/ICP-MS）為主，同時有一些探索性的方法如全反射X射線熒光光譜法（TXRF）。根據目前面臨的挑戰，未來研究需聚焦高靈敏度實時監測、新型前處理方法開發及智能化污染溯源，以應對先進制程的帶來的潔凈度挑戰，為半導體制造的可持續發展提供技術支撐。
關鍵詞：氣態分子污染物；酸性污染物；金屬污染物； 半導體制造；離子色譜法；電感耦合等離子體發射光譜與質譜（ICP-OES/ICP-MS）
中圖分類號：O65 文獻標識碼：A 文章編號：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)
半導體硅片表面金屬污染物分析技術研究進展
常燕1，史澤遠2，郝萍1，高一鳴1，王勇1，李更銀1,3，李春華*1
(1. 上海計量測試技術研究院，上海 201203；2. 中國電子技術標準化研究院，北京 100007；
3. 上海第二工業大學 能源與材料學院，上海，201209）
摘要:隨著半導體技術向5 nm及以下節點發展，硅片表面金屬雜質污染已成為制約芯片性能和良率的關鍵因素。系統綜述了硅片表面金屬污染物分析技術的研究進展與應用策略，介紹了金屬雜質污染的基本特性及其對器件性能的影響，以及主要的分析標準體系。重點闡述了氣相分解-電感耦合等離子體質譜法、全反射X射線熒光分析、二次離子質譜法、飛行時間二次離子質譜法、俄歇電子光譜法和X射線光電子能譜法等主要技術的原理特點與應用范圍，系統對比了各技術在檢測限、空間分辨率、元素覆蓋與化學狀態表征等方面的性能差異。在此基礎上，構建了基于污染物特性、分析目的和資源條件的技術選擇決策框架，提出了多技術互補分析體系的優化策略，并針對工藝監控、失效分析和研發優化等不同場景設計了系統化的技術組合方案。展望未來，分析技術將向更高靈敏度、更高空間分辨率和更好的實時監測能力方向發展，為先進工藝節點的污染控制提供更有力的技術支持。
關鍵詞: 硅片；表面金屬污染物；氣相分解-電感耦合等離子體質譜法；全反射X射線熒光分析；二次離子質譜法；俄歇電子光譜法；X射線光電子能譜法
中圖分類號：O657 文獻標識碼：A 文章編號：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-yin1,3, 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
電子化學品標準化現狀及展望
全燦
(中國計量科學研究院，北京 100029）
摘要：電子化學品是半導體、顯示面板、光伏等電子工業的核心配套材料，被譽為芯片產業的“生長激素”，廣泛應用于晶圓清洗、蝕刻、光刻、沉積等關鍵制程。電子化學品主要包括超凈高純試劑、光刻膠配套溶劑、特種氣體等卡脖子材料，其純度和雜質含量直接影響芯片產品性能。我國高度重視電子化學品的國產化生產，標準化是支撐我國半導體產業自主發展的關鍵技術支撐。首次系統分析了多晶硅、智能手機柔性電子材料等電子化學品在芯片制作過程中的應用及市場布局；研究了國際半導體產業協會（SEMI）代表性電子級溶劑、酸、堿以及電子特氣等代表性電子化學品的標準化概況以及我國電子化學品領域的相關政策以及標準化現狀；總結了我國電子級溶劑純度和痕量雜質領域相關標準物質研制及其量值溯源技術研究概況，包括系列高純溶劑標準物質、高純硅標準物質和超高純氦氣純度標準物質等為構建自主可控的半導體材料供應鏈提供了關鍵技術支撐。研究成果對推進電子化學品國產化進程、保障我國半導體產業安全、服務國家高質量發展戰略具有重要參考價值，尤其為破解我國高端電子化學品"生產工藝-產品標準-量值溯源"提供了系統性支撐。
關鍵詞：電子化學品；標準化；標準物質；半導體材料供應鏈
中圖分類號：TQ42/O6 文獻標識碼：A 文章編號：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
電子化學品前驅體材料中金屬雜質分析技術研究進展
李更銀1, 2，史澤遠3，李春華1，許劍光2，張星宇2，王俊2，常燕*1
(1. 上海計量測試技術研究院，上海 201203; 2. 上海第二工業大學 能源與材料學院，上海 201209；3. 中國電子技術標準化研究院，北京 100007)
摘要：隨著半導體制程特征尺寸縮小至納米級，前驅體材料中金屬雜質控制已成為影響器件性能和良率的決定性因素。闡述了電子化學品前驅體的定義、分類及標準體系現狀。系統梳理了固態、液態和氣態前驅體的樣品前處理技術，針對不同形態前驅體的特殊性質和分析需求，深入分析了電熱板濕法消解、微波消解、灰化法、熱揮發-酸溶解法、酸霧消解法、石墨熏蒸法、直接酸消解法、減壓蒸餾法、溶液吸收法、氣體吸收-水解混合法等關鍵技術的原理、適用條件和技術要點。論述了電感耦合等離子體質譜（ICP-MS）技術在前驅體分析中面臨的質譜干擾和基體效應問題，以及高分辨率質譜、反應/碰撞池技術等解決方案。在分析方法驗證與質量保證方面，針對前驅體材料缺乏標準參考物質、基體復雜多變、檢測限要求極低等挑戰，提出結合測量系統分析（MSA）與傳統驗證方法的綜合策略，通過系統評估重復性、再現性和關鍵變異因素，確保方法的可靠性。隨著半導體工藝邁入5 nm及以下節點，前驅體材料金屬雜質分析將向前處理與儀器分析技術融合、人工智能應用、在線監測等方向發展。加強方法標準和標準物質研制，建立完善的質量控制體系，對支撐電子化學品前驅體材料產業發展具有重要意義。
關鍵詞：電子化學品前驅體；金屬雜質分析；樣品前處理；電感耦合等離子體質譜；質譜干擾；基體效應；方法驗證
中圖分類號：O65 文獻標識碼：A 文章編號：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-yin1,2, 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
電子級無機酸中痕量陰陽離子檢測技術進展
王勇，常燕，郝萍，李春華，曹建雄，高一鳴*
（上海市計量測試技術研究院，上海 201203）
摘要: 集成電路產業的迅猛發展推動著全球半導體行業向高端制程邁進，濕電子化學品中無機酸作為集成電路產業的關鍵材料，其純度直接影響芯片制造的工藝穩定性和產品良率。相應地，電子級無機酸中陰陽離子雜質檢測技術的發展顯得尤為重要。離子色譜法因其檢測靈敏度高，快速方便和結果準確等優點，廣泛應用于濕電子化學品電子級無機酸中痕量陰離子的檢測，同樣地，電感耦合等離子體質譜法因其抗干擾能力強，動態范圍寬和快速準確分析等優點，廣泛應用于濕電子化學品電子級無機酸中痕量陽離子的檢測。簡要介紹了電子級無機酸中硝酸、氫氟酸、鹽酸、硫酸和磷酸的理化性質和在半導體工藝中的作用，并將國內外標準中的關鍵指標進行了列表對比，對近年來電子級無機酸中陰陽離子檢測技術的研究進展進行了綜述，重點介紹了各種無機酸在進行陰離子和陽離子檢測時樣品的前處理方法，容易遇到的檢測難點以及相應地解決方法。此外，還探討了濕電子化學品在半導體行業的未來發展趨勢。
關鍵詞：濕電子化學品；無機酸；陰陽離子；國內外標準；技術進展
中圖分類號：O657.63 文獻標識碼：A 文章編號：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
三重四極桿質譜技術在電子化學品中痕量元素檢測應用進展
曾遠*,2，賀兆波2，楊磊2，雷雯3，吳昊*1,2，池汝安1，李少平1,2
（1. 湖北三峽實驗室，湖北 宜昌 443007；2. 湖北興福電子材料股份有限公司，湖北 宜昌 443007；3.湖北工業大學，湖北 武漢 430068）
摘要：半導體工藝與技術的飛速發展促使集成電路制造的器件尺寸不斷縮小，對環境及原材料污染控制的要求愈發嚴格。隨著半導體制造技術邁向納米級，電子化學品的純度要求持續提升，檢測雜質水平也從微克/升（μg/L）降至皮克/升（pg/L）級別。在半導體器件制造中，痕量雜質元素及污染控制是關鍵環節，這些雜質可能來源于晶圓基板或電子化學品試劑，尤其是金屬離子和納米顆粒，會對器件性能和產量產生負面影響。因此，制造工廠需采用高純度化學試劑并嚴格控制雜質污染。電感耦合等離子體質譜（ICP-MS）憑借其高靈敏度、多元素同時檢測能力以及對復雜基質的良好耐受性，已成為高純電子化學品雜質檢測的首選技術之一。近年來，ICP-MS技術不斷創新，特別是三重四極桿串聯ICP-MS（ICP-QQQ）的出現，進一步提升了檢測性能，尤其適用于超高純電子化學品的檢測。總結了ICP-QQQ在關鍵電子化學品檢測痕量雜質元素方面的優勢與挑戰，詳細論述其在酸性化學品、有機化學品中金屬/非金屬雜質檢測的研究進展，特別針對高純有機化學品及實驗室本底控制等方法條件進行了深入探討。最后，對ICP-QQQ技術的發展趨勢進行了展望，并提出了未來研究方向，以期為相關領域研究提供參考。
關鍵詞：半導體工業；硅基材料；電子化學品；痕量雜質元素；三重四極桿串聯電感耦合等離子體質譜
中圖分類號：O65 文獻標識碼：A 文章編號：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-ping1,2（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
超凈高純試劑中微量有機雜質和水分的脫除進展
秦磊*，陳亮
（中石化（上海）石油化工研究院有限公司綠色化工與工業催化全國重點實驗室，上海 201208）
摘要：超凈高純試劑是集成電路、新型顯示、印刷電路板等行業中不可或缺的重要關鍵化工材料。隨著全球人工智能、物聯網、5G產業的迅速發展，帶動了國內集成電路等相關產業的發展，對超凈高純試劑的需求將進一步顯著增加。超凈高純試劑除對金屬離子和顆粒物有嚴格管控外，對產品中的有機雜質和水分殘留按照產品等級或者應用領域不同也有著非常苛刻的要求。超凈高純試劑中微量有機雜質和水分的存在會極大影響產品的使用效果，甚至會降低晶圓的良率。極低的有機雜質和水分脫除是超凈高純試劑純化技術的關鍵點，也是其制備的技術難點，特別是需要同步保證純化后產品的高純度和較高的回收率。雖然近幾年國內超凈高純試劑產業發展迅速，但是純化手段與國外先進企業還略有差距。為此，針對目前超凈高純試劑中的微量有機雜質和水分脫除方法進行了簡要綜述，特別對精餾法、吸附法、結晶法、膜分離法以及反應法的脫除技術原理以及應用情況展開了介紹，并結合集成電路產業未來發展方向，對超凈高純試劑純化技術提出了建議和展望。
關鍵詞：超凈高純試劑；有機雜質；水分；微量；分離方法
中圖分類號：O69 文獻標識碼：A 文章編號：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
【生化與藥用試劑】
聚β-氨基酯基因載體改性研究進展
張博1，袁梓諾1，陳綺琪1，曾明2，李湘1，熊梧琬*1
（1. 肇慶學院 環境與化學工程學院，廣東 肇慶 526061；2. 中山大學附屬第六醫院皮膚科，廣東廣州 510655）
摘要：在基因治療領域中，如何設計并制備出一種相容性好、轉染效率高和細胞毒性低的基因載體，并將其應用于基因傳遞過程一直是人們研究的熱點。當前，基因載體主要分為病毒類和非病毒類兩大類型。在臨床治療中，病毒類載體的轉染效率較高，但由于其存在整體安全性較低、制備工藝復雜和易引發免疫應答反應等缺點，大大限制了其在基因治療中的應用。非病毒類載體聚β-氨基酯（PBAEs），是利用邁克爾加成反應機理，由胺和丙烯酸酯類單體合成的一種聚合物，具備高細胞活性、低細胞毒性、原料易得、合成簡單以及結構多樣等優點，是一類有廣闊應用前景的非病毒基因載體材料。近年來，隨著聚β-氨基酯研究的深入，眾多的改進方法被應用于對其結構的改性優化，從而使其性能得到了持續的提升。主要從枝化、封端、側鏈修飾、末端修飾以及嵌段修飾5個方面對聚β-氨基酯的改性研究進展進行了綜述，并且對聚β-氨基酯的工業化生產和質量控制進行了討論，為基因治療領域的研究提供參考。
關鍵詞：聚β-氨基酯；陽離子聚合物；基因載體；改性；轉染效率
中圖分類號：O631 文獻標識碼：A 文章編號：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-wan1*(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】
淀粉微膠囊改性鎂鐵銅三元水滑石及其對聚氯乙烯材料性能的影響
張恒a，王佳悅a，藍心杏a，羅肖a,b，馬維勛a,b，趙良蓮a,c，朵興紅*a,b,c
(青海民族大學 a.化學與材料科學學院；b. 青藏高原資源化學與生態環境保護國家民委重點實驗室；c. 青海省應用物理化學重點實驗室，青海西寧 810007）
摘要：水滑石類化合物（LDHs）作為一種無鹵、無害且高效的無機阻燃劑，具有消煙、阻燃等多種功能，在阻燃領域極具開發潛力。但水滑石粒子易團聚，在聚合物基體中分散性差進而影響材料機械性能。為解決這一問題，采用馬鈴薯淀粉（PS）對MgFeCu-LDHs進行微膠囊包覆改性，合成了PS@MgFeCu-LDHs。利用X射線衍射（XRD）、傅里葉紅外光譜（FT-IR）、透射電子顯微鏡（TEM）對其進行了結構性表征；隨后將PS@MgFeCu-LDHs加入到聚氯乙烯（PVC）材料中，制備復合材料。并對其抑煙性能、阻燃性能、機械性能進行了測試。結果表明，PS@MgFeCu-LDHs/PVC復合材料具有良好的阻燃抑煙性能，4%PS@MgFeCu-LDHs/PVC復合材料的最大比光密度下降至14.63，相比于PVC的33.13，降幅達55.8%。由于淀粉的引入，PS@MgFeCu-LDHs能有效增加PVC的殘炭率，提高熱穩定性能。力學測試表明，PS@MgFeCu-LDHs在復合材料中的相容性較好。同時，極限氧指數（LOI）也提升至25.6，UL-94水平燃燒測試等級達HB級。研究結果為添加型無機阻燃劑提供了新策略，用以降低PVC材料的火災風險。
關鍵詞：聚氯乙烯；水滑石；微膠囊；阻燃；抑煙
中圖分類號：O61 文獻標識碼：A 文章編號：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 Henga, WANG Jia-yuea, Lan Xin-xinga, LUO Xiaoa,b, MA Wei-xuna,b, ZHAO Liang-liana,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
【分析與測試】
改進QuEChErs-同位素內標-UPLC-MS /MS快速測定禽蛋和雞肉中喹諾酮類藥物殘留及暴露風險水平研究
陳旭1，劉春波*2，張海燕2，包玉蘭2，張麗敏2，趙宏2
（1.內蒙古自治區中醫醫院，內蒙古呼和浩特 010010，2.呼和浩特市疾病預防控制中心，內蒙古呼和浩特 010010）
摘要：建立一種QuEChERS-同位素-UPLC-MS/MS方法，用于快速測定禽蛋和雞肉中6種喹諾酮類藥物的殘留；根據檢測數據分析內蒙古地區禽蛋和雞肉中喹諾酮類藥物的污染水平，使用喹諾酮類藥物的總危害商數（ΣQHQ）評估膳食暴露風險。通過改進QuEChERS前處理技術（提取液、吸附凈化劑）、色譜柱和流動相等條件優化實驗方法，將優化后的方法應用于233份禽蛋和雞肉樣品。使用T3色譜柱、V（5 mmol/L甲酸銨和0.1%甲酸水）?V（甲醇）=98?2和V（5 mmol/L甲酸銨和0.1%甲酸水）?V（甲醇）=2?98流動相、Discovery? DSC-18 SPE作吸附劑、V（5mmol/L甲酸銨和0.1%甲酸水）?V（乙腈）=2?98為提取液，6種喹諾酮類藥物色譜峰形尖銳，分離效果好，響應值高，在1~100 ng/mL范圍內線性關系良好，相關系數R≥0.9990，檢出限范圍為0.3~1 μg/kg，定量限范圍為1~3 μg/kg，在3個不同加標水平濃度點的回收率范圍為88.1%~117.1%，相對標準偏差范圍為0.6%~7.19%（n=6）。禽蛋中喹諾酮類藥物的檢出率為3.33%（4/120），雞肉中喹諾酮類藥物的檢出率為6.19%（7/113），總體檢出率為4.72%（11/233）。改進后的方法具有較低的檢出限和較高的準確度，能夠簡單快速地測定禽蛋和雞肉中的喹諾酮類藥物殘留。在喹諾酮類藥物的風險評估中，各年齡組的6種喹諾酮類藥物的QHQ均小于1，各年齡組的總危害商數（ΣQHQ）均小于1，風險處于可接受的水平。
關鍵詞：QuEChErs；同位素；超高效液相色譜串聯質譜法；喹諾酮類；膳食暴露風險
中圖分類號：O657;X04 文獻標識碼：A 文章編號：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 (ΣQHQ) 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 QHQ for the six quinolones in all age groups was below 1, and the total hazard quotient (ΣQHQ) 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
超高效液相色譜-質譜法測定環丙沙星中5種有關物質含量
許曉輝，李堅，吳福祥，杜銳滸，張曉萍，張生萍*，王小喬*
（蘭州市食品藥品檢驗檢測研究院，甘肅蘭州 730050）
摘要：環丙沙星中有關物質的殘留水平應控制在標準規定的限度范圍內，以保證其質量安全有效。建立了一種超高效液相色譜-串聯三重四極桿質譜法同時測定環丙沙星中5種有關物質（雜質A、B、C、E、H）含量的分析方法。樣品以乙腈超聲提取，經0.22 μm有機濾膜過濾，UPLC-MS/MS檢測，采用Waters ACQUITY BEH C18（2.1 mm×100 mm，1.7 μm）高性能通用性液相色譜柱分離，以水相為含0.1%甲酸-2 mmol/L乙酸銨的水溶液與有機相為含0.1%甲酸的乙腈溶液進行梯度洗脫，柱溫：30℃，進樣量：2 μL，流速：0.2 mL/min，采用Agilent噴射流電噴霧電離離子源，正離子下以多反應監測模式采集，外標法定量。結果顯示，5種有關物質在各自范圍內線性關系良好，線性相關系數R2均大于0.99，重復性的相對標準偏差≤5%，檢出限和定量限分別為0.058～0.42和0.19～1.3 ng/mL，3個水平加標回收率在71.3%～118.8 %，相對標準偏差在1.0%～7.5%，6批樣品中均檢出有關物質，含量均符合2020年版《中國藥典》限量要求。該方法前處理操作簡單，準確靈敏，重復性和穩定性良好，可用于環丙沙星中有關物質的質量控制。
關鍵詞：超高效液相色譜-質譜法；環丙沙星；有關物質；含量；測定；質量控制
中圖分類號：R917，O657 文獻標識碼：A 文章編號：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
【合成與應用】
2-喹啉酮化合物的合成研究進展
羅小芹，黃楨惠，何依倩，陳清，林寧*
（廣西中醫藥大學 藥學院 廣西壯瑤藥技術創新中心，廣西南寧 530200）
摘要：2-喹啉酮作為含氮雜環化合物中的重要成員，因其獨特的氮雜環共軛結構和多樣的生物活性，在藥物化學、材料科學及化學生物學等領域展現出重要的應用價值。該骨架不僅是構建復雜天然產物和功能分子的重要合成砌塊，也是構成多種藥物分子的核心結構單元，在抗菌（如喹諾酮類抗生素）、抗腫瘤（如蛋白激酶抑制劑）及抗炎等藥物研發中具有關鍵作用，受到合成化學與藥物化學領域的關注。隨著對2-喹啉酮化合物研究的不斷發展，近年其合成策略的創新成為化學研究的熱點。本文綜述了近年來2-喹啉酮骨架的合成研究進展，以合成其結構的反應類型為分類依據，介紹了從不同合成前體出發合成2-喹啉酮骨架的常用方法，例如光催化、過渡金屬催化、電化學合成等，并對各合成方法的反應機理、底物適用性、優勢和局限性進行分析，旨在為2-喹啉酮合成方法學的創新提供理論參考，同時為基于該骨架的藥物設計、功能材料開發及天然產物全合成等領域的發展提供技術路線參考，助力推動相關交叉學科的前沿研究。
關鍵詞：2-喹啉酮；藥效骨架；合成；反應機理；研究進展
中圖分類號：O621.3 文獻標識碼：A 文章編號：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進展
羅小芹，黃楨惠，何依倩，陳清，林寧*
（廣西中醫藥大學 藥學院 廣西壯瑤藥技術創新中心，廣西 南寧 530200）
摘要：2-喹啉酮作為含氮雜環化合物中的重要成員，因其獨特的氮雜環共軛結構和多樣的生物活性，在藥物化學、材料科學及化學生物學等領域展現出重要的應用價值。該骨架不僅是構建復雜天然產物和功能分子的重要合成砌塊，也是構成多種藥物分子的核心結構單元，在抗菌（如喹諾酮類抗生素）、抗腫瘤（如蛋白激酶抑制劑）及抗炎等藥物研發中具有關鍵作用，受到合成化學與藥物化學領域的關注。隨著對2-喹啉酮化合物研究的不斷發展，近年其合成策略的創新成為化學研究的熱點。本文綜述了近年來2-喹啉酮骨架的合成研究進展，以合成其結構的反應類型為分類依據，介紹了從不同合成前體出發合成2-喹啉酮骨架的常用方法，例如光催化、過渡金屬催化、電化學合成等，并對各合成方法的反應機理、底物適用性、優勢和局限性進行分析，旨在為2-喹啉酮合成方法學的創新提供理論參考，同時為基于該骨架的藥物設計、功能材料開發及天然產物全合成等領域的發展提供技術路線參考，助力推動相關交叉學科的前沿研究。
關鍵詞：2-喹啉酮；藥效骨架；合成；反應機理；研究進展
中圖分類號：O621.3 文獻標識碼：A 文章編號：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
向明麗a,b,c，曾亞玲a,b,c，姚佳倩a,b,c，劉文鋒*a,b,c，郭素琴a,b,c，李紅光*a,b,c
(五邑大學a. 藥學與食品工程學院，b. 華南生物醫藥大動物模型研究院，c. 廣東省醫學大動物模型重點實驗室，廣東 江門 529020)
摘要：肉桂酸源于肉桂皮，具有廣泛的生理活性。通過酯化反應合成新型肉桂酸衍生物，并評價此類化合物對α-葡萄糖苷酶活性的影響。首先，從含不同取代基的肉桂酸原料出發，在1-(3-二甲氨基丙基)-3-乙基碳二亞胺鹽酸鹽（EDCI）的縮合作用下，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，利用氫-1核磁共振（1HNMR），碳-13核磁共振（13CNMR）及高分辨質譜（HR-MS）確證目標化合物的化學結構，并通過體外活性測試方法評價此類化合物對α-葡萄糖苷酶的抑制作用和作用機制。最后，通過分子對接揭示化合物的作用機制。實驗結果顯示，(E)-3-(4-甲基苯基)-2-丙烯酸-4-羥甲基苯酯（1a）和(E)-3-(4-甲氧基苯基)丙烯酸-4-羥甲基苯酯（1b）對α-葡萄糖苷酶具有最強的抑制活性，它們的IC50值分別為（22.23± 2.21）和（38.23± 2.59）μmol/L，顯著低于阿卡波糖。酶動力學研究表明，化合物1a的抑制類型為混合型，而化合物1b的抑制類型為非競爭型。分子模擬結果表明，化合物1a和1b均能嵌插在α-葡萄糖苷酶的活性口袋中，并與口袋中的氨基酸殘基形成氫鍵。此外，化合物結構中的苯環和能與活性口袋中的疏水區域形成相互作用。因此，實驗結果不僅揭示了肉桂酸衍生物作為α-葡萄糖苷酶抑制劑的構效關系，更為后續通過結構修飾進一步提高抑制活性奠定了堅實的理論基礎。
關鍵詞：肉桂酸；合成；α-葡萄糖苷酶；抑制；作用機制
中圖分類號：O61 文獻標識碼：A 文章編號：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-lia,b,c, ZENG Ya-linga,b,c, YAO Jia-qiana,b,c, LIU Wen-feng*a,b,c, GUO Su-qina,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
