【特约专题】

氮化硼纳米材料用于药物递送的研究进展

戚凯通，任婷，孙国辉，张娜，赵丽娇^*，钟儒刚

（北京工业大学 环境与病毒肿瘤学北京市重点实验室，北京  100124）

摘要：氮化硼(BN)纳米材料作为新一代药物载体，凭借其独特的结构特性和优异的物理化学性能，近年来已成为一类新型的药物递送体系。系统阐述了 BN纳米管、纳米片及多孔材料的合成和药物递送的最新应用进展。研究表明，BN 材料不仅具有超高的比表面积和卓越的生物相容性，更能通过表面功能化来实现智能响应释药，包括 pH 敏感、光热触发和磁性靶向等多种模式。通过创新的功能化修饰策略，如叶酸受体介导的主动靶向、聚乙二醇化改性和刺激响应聚合物包覆，BN 纳米载体成功解决了传统递药系统靶向性差，毒副作用大等关键问题。特别是在肿瘤治疗领域，BN 基载药系统展现出双重优势：既能显著提高药物在病灶部位的富集效率，又可实现微环境响应的可控释放，为突破血脑屏障等治疗瓶颈提供了新思路。尽管 BN 纳米材料在载药量，靶向性和生物安全性等方面已取得重要进展，其临床应用仍面临规模化制备、长期毒理评价等挑战。未来研究应着力于开发多功能集成化的 BN 载体，探索其在基因治疗、免疫调节等新兴领域的应用，推动纳米医学向精准化，智能化方向发展，以期为肿瘤治疗提供创新解决方案，更为新型药物递送系统的设计开辟崭新途径。

关键词：氮化硼纳米材料；合成；功能化；药物递送；肿瘤靶向

中图分类号：O63       文献标识码：A         文章编号：0258-3283（2025）--

DOI：10.13822/j.cnki.hxsj.2025.0086

Research Progress on the Application of Boron Nitride Nanomaterials in Drug Delivery QI Kai-tong, REN Ting, SUN Guo-hui, Zhang Na, ZHAO Li-jiao^*, ZHONG Ru-gang (Beijing Key Laboratory of Environment and Viral Oncology, Beijing University of Technology, Beijing 100124, China)

Abstract: Boron nitride (BN) nanomaterials, as a new generation of drug carriers, have recently emerged as novel drug delivery systems due to their unique structural characteristics and excellent physicochemical properties. This article systematically reviewed the latest advances in the synthesis and drug delivery of BN nanotubes, nanosheets and porous materials. Studies have shown that BN materials not only have an extremely high specific surface area and excellent biocompatibility, but also can achieve intelligent responsive drug release through surface functionalization, including multiple modes such as pH-sensitive, photothermal triggered, and magnetic targeting. Innovative fictionization strategies such as folate receptor-mediated active targeting, PEGylation, and stimulus-responsive polymer coating have enabled BN nanocarriers to overcome critical issues associated with traditional drug delivery systems such as poor targeting efficiency and significant toxicity. Particularly in tumor therapy, BN-based drug delivery systems have demonstrated dual advantages: they can not only significantly enhance the drug accumulation at the lesion sites, but also enable controlled release triggered by the tumor microenvironment, providing new ideas for breaking through therapeutic bottlenecks such as the blood-brain barrier. Although BN nanomaterials have achieved significant progress in drug loading capacity, targeting and biosafety, their clinical application still faces challenges such as large-scale manufacturing and long-term toxicological evaluation. Future research should focus on developing multifunctional integrated BN vectors, exploring their applications in emerging fields such as gene therapy and immunomodulation. These efforts will promote the development of nanomedicine towards greater precision and intelligence, with the expectation of providing innovative solutions for tumor treatment and opening up a brand-new path for the design of next generation drug delivery systems.

Key words: boron nitride nanomaterials; synthesis; functionalization; drug delivery; targeting therapy of tumor

咔唑类化合物抗糖尿病活性研究进展

罗霜^a,b，赵丽^a,b，赵燕^a,b，马雪^a，王广成^*a

(贵州医科大学 a. 中药功效成分发掘与利用全国重点实验室 民族药与中药开发应用教育部工程研究中心 贵州省民族药与中药开发应用工程技术研究中心；b. 药学院，贵州 贵阳  561113)

摘要：糖尿病属于慢性代谢类病症，是世界范围内导致死亡和残疾的重要原因，严重威胁着人类健康。其中大约90%的糖尿病是2型糖尿病（T2DM），其主要病因是胰岛素抵抗或胰岛素分泌异常。T2DM的典型特征表现为持续性高血糖，长期血糖控制不良可进一步引发肾病、心血管疾病、肥胖、失明和高血压等多种并发症。这些并发症不仅显著降低患者生活质量，更是导致糖尿病患者致残和致死的主要原因。咔唑类化合物是一类重要的含氮杂环化合物，因其抗菌、抗癌、抗氧化和抗炎等多种生物和药理特性而在药物化学领域受到广泛关注。近年来，咔唑类化合物在抗糖尿病药物研发领域展现出广阔前景，国内外学者基于咔唑骨架设计合成了大量具有抗糖尿病活性的小分子化合物。根据抗糖尿病的作用靶点如α-葡萄糖苷酶、α-淀粉酶、过氧化物酶体增殖物激活受体（PPARs）和蛋白酪氨酸磷酸酶1B（PTP1B）等，对近年来文献报道的具有抗糖尿病活性的天然或合成来源的咔唑类化合物进行梳理与总结，以期为后续新型抗糖尿病药物的研发提供参考。

关键词：2型糖尿病；咔唑；作用靶点；α-葡萄糖苷酶；α-淀粉酶

中图分类号：O62         文献标识码：A          文章编号：0258-3283（2025）--

DOI：10.13822/j.cnki.hxsj.2025.0107

Research Progress on the Antidiabetic Activity of Carbazole Derivatives LUO Shuang^a,b, ZHAO Li ^a,b, ZHAO Yan ^a,b, MA Xue ^a, WANG Guang-cheng^* a (a. Guizhou Provincial Engineering Research Center for the Development and Application of Ethnic Medicine and TCM, Engineering Research Center for the Development and Application of Ethnic Medicine and TCM (Ministry of Education), State Key Laboratory of Discovery and Utilization of Functional Components in Traditional Chinese Medicine; b. School of Pharmacy, Guizhou Medical University, Guiyang 561113, China )

Abstract: Diabetes is a chronic metabolic disorder and a leading cause of death and disability worldwide, posing a serious threat to human health. Approximately 90% of diabetes is type 2 diabetes mellitus (T2DM), primarily caused by insulin resistance or abnormal insulin secretion. The hallmark of T2DM is persistent hyperglycemia, and poor long-term glycemic control can further lead to various complications such as nephropathy, cardiovascular disease, obesity, blindness, and hypertension. These complications significantly reduce the quality of patients’ life and are major contributors to disability and mortality of diabetic patients. Carbazole derivatives, an important class of nitrogen-containing heterocyclic compounds, has attracted widespread attention in medicinal chemistry due to their diverse biological and pharmacological properties, such as antibacterial, anticancer, antioxidant, and anti-inflammatory effects. In recent years, carbazole compounds have shown great potential in antidiabetes drug research and development. Research worldwide have designed and synthesized numerous small molecules with antidiabetes activity based on the carbazole scaffold. This review summarized recent natural and synthetic carbazole derivatives with antidiabetic activity, focusing on key therapeutic targets such as α-glucosidase, α-amylase, peroxisome proliferator activated receptors (PPARs) and protein tyrosine phosphatase 1B (PTP1B). The aim is to provide reference for the subsequent development of novel antidiabetes agents.

Key words: type 2 diabetes; carbazole; target; α-glucosidase; α-amylase

基于力达霉素的重组融合蛋白抗体偶联药物

结构稳定性的计算分析

刘梦婷，郭一涵，孟姿，刘思雨，韩田超，赵文伯

（郑州师范学院 化学化工学院，河南 郑州  450000）

摘要：力达霉素是我国从土壤中筛选出的一个新的烯二炔类抗肿瘤抗生素，以力达霉素(LDP-AE)为基础，制备的重组融合蛋白（LDP-D3、Fv-LDP、Fv-LDP-D3）及其抗体偶联药物（LDP-D3-AE、Fv-LDP-AE、Fv-LDP-D3-AE）具有良好的抗肿瘤活性，但其相关蛋白结构尚未解析，所合成的抗体偶联药物结构是否稳定也尚未验证。基于以上研究背景，采用AlphaFold3对Fv-LDP、LDP-D3、Fv-LDP-D3重组融合蛋白的三级折叠结构进行预测，将LDP及3种重组融合蛋白分别与AE对接得到LDP-AE、LDP-D3-AE、Fv-LDP-AE和Fv-LDP-D3-AE 4种复合物，通过动力学模拟及结合自由能计算分析了4种复合物结构的稳定性，其中Fv是抗EGFR单链可变区片段，D3是人血清白蛋白（HSA）的结构域Ⅲ，LDP是力达霉素（LDM）的辅基蛋白，AE是LDM的活性烯二炔发色团。分子对接结果显示4种蛋白质均能与AE形成稳定结构，且均结合在LDP片段部分。采用多种方法对动力学模拟结果进行深入分析探讨，不同的分析方法之间可以相互印证，结果表明LDP、LDP-D3、Fv-LDP和Fv-LDP-D3均能与AE形成结构稳定的复合物，其中范德华力在这4个复合物形成的过程中起着重要作用，氢键作用也有相当一部分的贡献。

关键词：蛋白质结构预测；分子对接；分子动力学模拟；抗体偶联药物；力达霉素

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.2025.0040

Computational Analysis of Structural Stability for Recombinant Fusion Protein-based Antibody-Drug Conjugates Derived from Lidamycin LIU Meng-ting, GUO Yi-han, MENG Zi, LIU Si-yu, HAN Tian-chao, ZHAO Wen-bo* (School of Chemistry and Chemical Engineering, Zhengzhou Normal University, Zhengzhou 450000,China)

Abstract: Lidamycin is a novel enediyne-class antitumor antibiotic isolated from soil samples in China. The recombinant fusion proteins (LDP-D3, Fv-LDP, Fv-LDP-D3) and their antibody-conjugated drugs (LDP-D3-AE, Fv-LDP-AE, Fv-LDP-D3-AE) ,constructed based on lidamycin (LDP-AE), have demonstrated potent anti-tumor activity. However, the structural information of these protein remain unsolved, and the stability of the synthesized antibody?drug conjugates has yet to be confirmed. To address this gap, AlphaFold3 was utilized to predict the tertiary folding structures of the recombinant fusion proteins Fv-LDP, LDP-D3, and Fv-LDP-D3. These proteins were then docked with AE, yielding four complexes: LDP-AE, LDP-D3-AE, Fv-LDP-AE, and Fv-LDP-D3-AE. The structural stability of these four complexes was analyzed through molecular dynamics simulations and binding free energy calculations. Specifically, Fv represented the single-chain variable fragment (scFv) of anti-EGFR, D3 was domain III of human serum albumin (HSA), LDP was the ligand-binding protein of lidamycin (LDM), and AE refered to the active enediyne chromophore of LDM. Molecular docking results revealed that all four proteins form stable structures with AE, with binding occurring specifically within the LDP fragment regions. Multiple analytical methods were applied to further analyze the molecular dynamics simulation results, and the results corroborated each other. The results demonstrate that LDP, LDP-D3, Fv-LDP, and Fv-LDP-D3 can all form structurally stable complexes with AE with Van der Waals forces playing a crucial role in complexes formation and hydrogen bonding providing additional stability.

Key words: Protein structure prediction; molecular docking; molecular dynamics simulation; antibody-conjugated drugs; lidamycin

【功能材料】

具有AIE性质Cu（II）和Zn（II）离子荧光探针的

合成及应用

刘杰^*，田文慧，朱雪宇，李慧，李子康，刘喜，张凤祥

（阜阳师范大学 化学与材料工程学院，安徽 阜阳  236037）

摘要：以4-二乙氨基水杨醛和丙二酸二乙酯为原料，通过Knoevenagel缩合关环（中间体Ⅰ）、水解脱羧（中间体Ⅱ）、Vilsmeier反应（中间体Ⅲ）、亲核加成反应，合成了目标化合物7-二乙氨基-3-甲酰基香豆素（2’-噻吩甲酰）腙（L），通过核磁共振谱（¹HNMR、¹³CNMR）进行结构表征。在研究其紫外光谱、荧光光谱和聚集诱导发光基础上，探索了其离子识别应用。结果表明：在四氢呋喃溶液中，探针L对Cu²⁺呈选择性荧光淬灭识别，而对Zn²⁺呈比率型荧光识别，具有精准的离子识别能力和较好的检测灵敏度，受到其他离子的干扰较小，并且反应前后伴有明显的颜色变化（在365 nm紫外灯照射下，加入铜离子后，荧光淬灭；加入锌离子后，由绿色变为黄色）。Job’s 曲线显示，探针L与Cu²⁺、Zn²⁺的物质的量之比为1:1和2:1，缔合常数K_b分别为5.18×10⁵、1.51×10⁶ L/mol，检出限分别为5.52×10^-7、1.13×10^-6 mol/L，均低于世界卫生组织对饮用水中Cu²⁺和Zn²⁺所允许的最高浓度。实验结果表明，该荧光探针在环境监测领域具有潜在应用价值，有望用于食品和水环境中Cu²⁺和Zn²⁺的检测。

关键词：席夫碱；聚集诱导发光；光学性质；比率型荧光探针；铜离子和锌离子识别

中图分类号：O657.31          文献标识码: A          文章编号：0258-3283（2025）--

DOI：10.13822/j.cnki.hxsj.2025.0054

Synthesis and Application of Cu (II) and Zn (II) Ionic Fluorescent Probes with AIE Properties LIU Jie*, TIAN Wen-hui, ZHU Xue-yu, LI Hui, LI Zi-kang, LIU Xi, ZHANG Feng-xiang (School of Chemistry and Materials Engineering, Fuyang Normal University, Fuyang 236037, China)

Abstract: Target compound 7-diethylamino-3-formylcoumarin (2 '- thienoyl) hydrazone (L) was synthesized from 4-diethylaminosalicylaldehyde and diethyl malonate through Knoevenagel condensation cyclization (intermediate I), hydrolytic decarboxylation (intermediate II), Vilsmeier reaction (intermediate III), and nucleophilic addition reaction. The structure was characterized by nuclear magnetic resonance spectroscopy (¹H-NMR, ¹³C-NMR). Based on the study of its UV spectrum, fluorescence spectrum, and aggregation induced emission (AIE), its ion recognition applications were explored. The results showed that in tetrahydrofuran solution, probe L selectively quenched fluorescence for Cu²⁺and displayed a ratio type fluorescence recognition for Zn²⁺, demonstrating precise ion recognition ability and good detection sensitivity. It was less affected by interference from other ions, with significant color changes before and after the reaction (fluorescence quenching occurred upon adding copper ions under 365 nm UV light; the color changed from green to yellow upon adding zinc ions). The Job’s curve showed that the stoichiometric ratios of probe L to Cu²⁺ and Zn²⁺ were 1:1 and 2:1, respectively, with binding constants K_b of 5.18×10⁵ and 1.51×10⁶ L/mol. The detection limits were 5.52×10^-7 and 1.13×10^-6 mol/L, respectively, which are both lower than the maximum allowable concentrations of Cu²⁺and Zn²⁺in drinking water as per the World Health Organization. The experimental results indicate that the fluorescent probe has potential application in environmental monitoring and is expected to be used for the detection of Cu²⁺and Zn²⁺in food and water environments.

Key words: schiffbase; aggregation induced emission; optical properties; ratiometric fluorescent probe; identification of copper and zinc ions

偕胺肟基亚硝酸盐荧光探针及分析应用

李静怡¹，杨腾宇¹, 陶健², 赵林萍³, 屈凌波^1,2，杨冉^*1,2

（1. 郑州大学 化学学院 河南省功能分子绿色构建与生物分析重点实验室 中原食品实验室, 河南 郑州  450001；2. 国家市场监督管理总局重点实验室（食品安全快速检测与智慧监管技术），河南 郑州  450003；3. 郑州中标检测技术有限公司，河南 郑州  450001)

摘要：亚硝酸盐作为环境与食品中常见污染物，其快速灵敏检测对公共健康保障具有重要意义。研究基于罗丹明800与羟胺开发了一种新型水溶性荧光探针Rh-PAO，其偕胺肟结构在强酸性条件下与亚硝酸盐（NO₂^⁻）通过重氮化反应生成NO⁺，导致探针红色荧光快速猝灭，并伴随溶液颜色由蓝色变为无色。该反应可在5 min内完成，且探针在50倍浓度共存离子（如Fe³⁺、NO₃^⁻等）存在下仍保持高选择性，抗干扰能力显著。基于荧光光谱与紫外-可见吸收光谱的双模检测方法，Rh-PAO对亚硝酸盐的检出限分别达9.7×10^-8和8.6×10^-8 mol/L，灵敏度较传统Griess比色法（检出限~10^-7 mol/L）及苯二胺类探针提升2～3个数量级。该方法成功应用于瓶装水与湖水样本中亚硝酸盐的检测，加标回收率为97.4%～112.9%，相对标准偏差（RSD）低于3.87%。研究进一步结合小型加热装置构建便携式检测系统，可在现场实现亚硝酸盐的可视化快速分析。通过偕胺肟反应位点的设计策略，探针的重氮化反应速率与水溶性显著提升，解决了传统苯二胺结构反应速度慢、水溶性差的缺陷。工作为亚硝酸盐的高效检测提供了新方法，在环境水质监测与食品安全领域展现出重要应用潜力。

关键词：亚硝酸盐（NO₂^-）；偕胺肟；荧光探针；快速检测；双模检测

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.2025.0131

Amidoxime-Based Fluorescent Probe for Nitrite Detection and Analytical Applications LI Jing-yi¹, YANG Teng-yu¹, TAO Jian², ZHAO Lin-ping³, QU Ling-bo^1,2, YANG Ran^*1,2 (1. Zhongyuan Food Laboratory, Key Laboratory of Functional Nanomaterial and Bioanalysis of Functional Molecules in Henan Province, College of Chemistry, Zhengzhou University, Zhengzhou 450001, China; 2. Key Laboratory of Food Safety Quick Testing and Smart Supervision Technology for State Market Regulation, Zhengzhou 450003, China; 3. Zhengzhou Zhongbiao Testing Technology Co., Ltd., Zhengzhou, 450001, China)

Abstract: Nitrite, a common contaminant in both environmental and food samples, poses a significant threat to public health. Therefore, its rapid and sensitive detection is of great importance. In this study, a novel water-soluble fluorescent probe, Rh-PAO, was developed based on rhodamine 800 and hydroxylamine. The amidoxime moiety of the probe undergoes diazotization with nitrite (NO₃^⁻) under strongly acidic conditions to produce NO⁺, resulting in a rapid quenching of the red fluorescence and a distinct color change of the solution from blue to colorless. This reaction was completed within 5 minutes. The probe exhibits high selectivity and anti-interference capability, maintaining high specificity even in the presence of 50-fold concentrations of coexisting ions (e.g., Fe³⁺, NO₃^⁻, etc.). demonstrating remarkable immunity to interference. A dual-mode detection strategy using both fluorescence and UV-visible absorption spectroscopy was established. The detection limits of nitrite was 9.7×10⁻⁸ and 8.6×10⁻⁸ mol/L, respectively, representing a 2～3 order of magnitude improvement in sensitivity compared to the traditional Griess colorimetric method (detection limit ~10⁻⁷ mol/L) and the phenylenediamine-based probe. This method was successfully used to determine nitrite levels in bottled and lake water samples, achieving recoveries ranging from 97.4% to 112.9% and relative standard deviations (RSDs) below 3.87%. Furthermore, a portable detection system was constructed by integrating a miniaturized heating device, enabling on-site and visual detection of nitrite. The design strategy for the amidoxime reactive site significantly enhanced the diazotization reaction rate and water solubility of the probe, overcoming the limitations of the traditional phenylenediamine-based probes in terms of slow response and poor aqueous solubility. This work provides a new, efficient method for detecting nitrite and has important potential applications in environmental water quality monitoring and food safety.

Key Words: nitrite (NO₂^-); amidoxime; fluorescent probe; quick detection; dual-mode detection

ART-N,P-CQDs的制备及其对药品中Fe(Ⅲ)的荧光检测

吴楚仪^{a, b}，吕枭^{a, b}，李华辉^{a, b}，张荩之^{a, b}，吴煜琳^{a, b}，黎天云^{a, b}，赵丹华^{*a, b}

（ 广东第二师范学院 a. 化学与材料科学学院；b. 环境材料与资源利用研究中心，广东 广州  510303）

摘要：以蔗糖为碳源，磷酸二氢铵为氮与磷源，通过一步水热法制备了一种耐酸型氮、磷掺杂碳量子点(ART-N,P-CQDs)作荧光探针，利用透射电镜(TEM)、傅里叶红外光谱(FT-IR)、纳米粒度分析仪、X-射线光电子能谱(XPS)、紫外分光光度计和荧光分光光度计对ART-N,P-CQDs的结构及其光学性质进行表征分析。结果显示，ART-N,P-CQDs为平均粒径1.7 nm的球形结构，其表面含有丰富的羟基、羧基、胺基、磷酸酯基等丰富的含氮、磷、氧的官能团，具有激发独立性的蓝色荧光，荧光量子产率为4.7%。鉴于Fe(Ⅲ)对ART-N,P-CQDs具有荧光猝灭效应，且为了准确检测Fe(Ⅲ)，需将其置于酸性环境以防止三价铁水解。从而构建了一种能在酸性环境下检测微量Fe(Ⅲ)的新方法。该方法线性方程为F₀/F=0.00364c(Fe³⁺)+0.9901（R²=0.9942），检出限为1.49 μmol/L，线性范围为10~100 μmol/L，能量转移猝灭和静态猝灭过程是致使ART-N,P-CQDs荧光猝灭的原因。ART-N,P-CQDs在一定酸性环境、离子强度及干扰离子共存的条件下检测体系仍具有良好的荧光稳定性，将该方法应用于补铁药品中微量铁的测定，其加标回收率为94.59%~99.53%，结果令人满意。该方法操作简便，可用于市面上补铁药片中铁含量的检测，具有一定的应用前景。

关键词： 耐酸性；氮、磷掺杂的碳量子点；激发独立性；Fe(Ⅲ)检测；荧光探针

中图分类号： O657.31; X832      文献标识码： A               文章编号：0258-3283（2025）--

DOI：10.13822/j.cnki.hxsj.2025.0080

Preparation of ART-N,P-CQDs and Fluorescence Detection of Fe(Ⅲ) in Drugs WU Chu-y^{a, b}, LV Xiao^a,b, LI Hua-hui^a,b, ZHANG Jin-zhi^a,b, WU Yu-lin^a,b, LI Tian-yun^a,b, ZHAO Dan-hua^*a,b (a. College of Chemistry and Materials Science; b. Research Center for Environmental Materials and Resource Utilization, Guangdong University of Education, Guangzhou 510303, China）

Abstract：Using sucrose as carbon source and ammonium dihydrogen phosphate as nitrogen and phosphorus sources, acid-resistance type nitrogen and phosphorus doped carbon quantum dots (ART-N,P-CQDs) were synthesized by a one-step hydrothermal method and applied as fluorescent probes. The structure and optical properties of ART-N, P-CQDs were characterized by transmission electron microscopy (TEM), Fourier transform infrared spectroscopy (FT-IR), nanoparticle size analyzer, X-ray photoelectron spectroscopy (XPS), UV-visible absorption spectrum and fluorescence spectrophotometer. The results showed that ART-N,P-CQDs had a spherical structure with an average particle size of 1.7 nm, and their surfaces were rich in functional groups such as hydroxyl, carboxyl, amine, phosphate containing nitrogen, phosphorus and oxygen atoms. The quantum dots exhibits bright blue fluorescence with excitation independence and a fluorescence quantum yield of 4.7%. Considering the fluorescence quenching effect of Fe(III) and the need for accurate detection in acidic environments to prevent hydrolysis, a new method was developed for detecting trace amounts of Fe(III) under acidic conditions. The linear relationship was given by the equation : F₀/F=0.00364c(Fe³⁺)+0.9901 (R²=0.9942), with a limit of detection of 1.49 μmol/L and a linear range of 10 ~ 100 μmol/L. The fluorescence quenching mechanism was attributed to energy transfer quenching and static quenching. The detection system maintained good fluorescence stability under acidic conditions, varying ionic strength, and coexistence of interfering ions. The method was successfully applied to the determination of trace iron in commercial iron supplementation, yielding spiked recoveries of 94.59% to  99.53% with satisfactory results. Owing to its operational simplicity and reliability, the proposed method demonstrates promising potential for iron quantification in commercially iron supplements.

Key words: acid resistance; nitrogen and phosphorus doped carbon quantum dots; excitation independence; detection of Fe(Ⅲ) in drugs; fluorescence probe

木质素-纤维素多功能性复合材料的研究进展

李美婵，李贺，李灿，付泳盛，李君，李德强^*

（新疆农业大学 化学化工学院, 新疆 乌鲁木齐  830052）

摘要：近年来，随着环保意识的提升和可持续发展战略的推进，开发绿色环保的生物基材料来替代传统石油基塑料已成为材料科学领域的研究热点。其中，纤维素作为自然界储量最丰富的生物质资源，因其分子链上含有大量羟基而具有优异的成膜性、可再生性和可降解性。然而，纤维素基材料在紫外线屏蔽性、阻燃性及抗氧化性能等方面的不足，严重限制了其在高附加值领域的应用。在此背景下，木质素因其独特的分子结构而备受关注。木质素分子中富含的芳香环结构和多种活性官能团，使其具有出色的热稳定性、抗氧化性以及优异的紫外屏蔽性能。这些特性可使木质素有效地拓展纤维素的应用范围，同时保持其可降解特性。基于当前研究现状，系统综述了木质素-纤维素复合材料的最新研究进展，重点分析了木质素对纤维素基材料阻燃性、紫外屏蔽性、抗氧化性和抗菌性等关键性能的影响机制。此外，还探讨了该领域发展面临的主要挑战和机遇，为开发新一代多功能性生物基功能性复合材料提供了重要参考。

关键词：木质素；纤维素；复合材料；生物质资源；功能材料

中图分类号：O63     文献标识码：A       文章编号：0258-3283（2025）--

DOI：10.13822/j.cnki.hxsj.2025.0079

Research Progress of Lignin-Cellulose Multifunctional Composites LI Mei-chan, LI He, LI Can, FU Yong-sheng, LI Jun, LI De-qiang^*  (College of Chemistry and Chemical Engineering, Xinjiang Agricultural University, Urumqi 830052, China）

Abstract：In recent years, the growing awareness of environmental protection and the advancement of sustainable development strategies have propelled the development of environmentally friendly bio-based materials as alternatives to traditional petroleum-derived plastics, making this a major research focus in materials science. Cellulose, the most abundant biomass resource in nature, exhibits remarkable film-forming properties, renewability, and biodegradability owing to the high density of hydroxyl groups along its molecular chain. Nevertheless, its limitations in ultraviolet shielding, flame retardancy, and antioxidant properties hinder broader applications in high-value field. In this context, lignin has garnered substantial attention due to its distinctive molecular structure. The aromatic ring structures and diverse reactive functional groups inherent in lignin molecules provide remarkable thermal stability, antioxidant capacity, and superior ultraviolet shielding performance. These characteristics enable lignin to effectively expand the application scope of cellulose, while maintaining its biodegradability. Based on the current research status, this paper systematically reviews the latest advancements in lignin-cellulose composite materials, with an emphasis on elucidating the mechanisms by which lignin influences key properties such as flame retardancy, UV resistance, antioxidant capacity, and antibacterial activity of cellulose-based materials. Furthermore, this paper also addressed the major challenges and opportunities in this field, offering valuable insights for the development of next-generation multifunctional bio-based functional materials.

Key words：lignin; cellulose; composite material; biomass resources; function materials

【分离提取技术】

响应面法优化叶黄素酯提取及对癌细胞生长影响研究

陈本书a, 罗爱芹^a, 丛勇^b, 梁阿新^a, 李紫媛^a, 罗茂国b, 孙立权^*a,b

（北京理工大学 a. 生命学院；b. 生物与医学工程公共实验中心，北京  100081）

摘要：采用响应面法优化超速破碎提取万寿菊中叶黄素酯的提取工艺参数，并研究该提取方法提取的叶黄素酯提取物抗癌生物活性。在单因素实验基础上，确定超速破碎提取次数、提取时间、料液比3个因素为主要影响提取工艺的因素，以叶黄素酯提取率为评价指标，研究超速破碎提取的最佳工艺参数，同时设置不同浓度叶黄素酯（20、40、80 µg/mL），通过细胞存活率和凋亡率检测实验研究叶黄素酯对HeLa细胞生长的影响。当超速破碎提取法提取转速为3500 r/min，提取次数为3次，提取时间为9 min，料液比为1:19（g/mL），得到叶黄素酯提取率为15.66 %。通过CCK-8试剂盒检测细胞存活率，FITC-Annexin V/PI流式细胞仪检测细胞凋亡率，实验结果表明，叶黄素酯对HeLa细胞生长具有抑制作用，随着叶黄素酯浓度增加，其抑制效果增强，其中当叶黄素酯浓度为80 μg/mL时， HeLa细胞存活率降低近50%。超速破碎提取法能效高、低耗提取万寿菊中叶黄素酯，为工业化生产提供技术支撑，同时研究结果表明万寿菊提取物中叶黄素酯能够有效抑制Hela细胞生长。

关键词：万寿菊；叶黄素酯；超速破碎提取；响应面法；抗癌

中图分类号：O657.72；R284.2             文献标识码：A     文章编号：0258-3283（2025）--

DOI：10.13822/j.cnki.hxsj.2025.0072

Optimization of lutein ester extraction by response surface method and its effect on cancer cell growth CHEN Ben-shu^a，LUO Ai-qin^a, CONG Yong^b, LIANG A-xin^a, LI Zi-yuan^a, LUO Mao-guo^b, SUN Li-quan^*a,b (a. School of Life Science; b. Biological & Medical Engineering Core Facilities, Beijing Institute of Technology, Beijing 100081, China)

Abstract： This study aims to optimize the parameters for ultra-speed crushing-assisted extraction of lutein esters from marigold flowers using response surface methodology, and to evaluate the anticancer bioactivity of the resulting extract. Based on single-factor experiments, three critical parameters: number of extraction cycles, extraction time, and solid-to-liquid ratio, were selected for process optimization, with lutein esters yield as the evaluation metric, Additionally, lutein esters solutions at concentrations of 20, 40, and 80 µg/mL were tested to assess their effects on HeLa cell viability by CCK-8 assay and apoptosis by FITC-Annexin V/PI flow cytometry. The optimal extraction conditions were determined as follows: rotational speed of 3500 r/min, 3 extraction cycles, 9 min of extraction time, and a solid-to-liquid ratio of 1:19 (g/mL), achieving a lutein esters extraction yield of 15.66%. Cell viability was measured by CCK-8 kit, and the apoptosis rate was detected by FITC-Annexin V/PI flow cytometry. Experimental results demonstrated dose-dependent inhibitory effects of lutein esters on HeLa cell proliferation; with the increase of lutein esters concentration, the inhibitory effect was enhanced. At 80 µg/mL, lutein esters reduced HeLa cell viability by approximately 50%. The ultra-speed crushing-assisted extraction method enables efficient and low-cost extraction of lutein esters from marigold flowers, providing a viable strategy for industrial-scale production. Furthermore, the lutein esters extract exhibits potent inhibitory activity against HeLa cell growth, highlighting its potential as a natural anticancer agent.

Key words: marigold; lutein esters; ultra-speed crushing extraction; response surface methodology; anti-cancer

【化学品与环境】

响应面法优化高效液相色谱-电感耦合等离子体质谱联用法分析环境地表水中的形态砷

牛倩^*，张军伟

(洛阳生态环境监测中心，河南 洛阳  471000)

摘要：针对传统检测方法在复杂基质中分离效率不足的问题，首次将响应面法（RSM）与高效液相色谱-电感耦合等离子体质谱（HPLC-ICP-MS）联用技术结合，建立了一种高灵敏度环境地表水中砷酸盐(As(V))、亚砷酸盐(As(III))、一甲基砷(MMA)、二甲基砷(DMA)、砷甜菜碱(AsB)、砷胆碱（AsC）6种形态砷的分析方法。通过Box-Behnken设计优化流动相pH（6.0 ~7.0）、甲醇比例（10% ~ 20%）及进样量（20~40 μL），成功的构建了二次回归模型(R_Adj²=0.951)，利用响应面法优化得出最优条件，研究发现pH与甲醇交互作用显著影响分离效率，最优条件为pH 6.7、甲醇13%、进样量28 μL，总分离度达11.4±0.3。采用Hamilton PRP-X100色谱柱与梯度洗脱程序，6种形态砷（As(III)、As(V)、MMA、DMA、AsB、AsC）均能在12 min内实现基线分离（分离度>1.5），各形态砷检出限为0.06 ~ 0.17 μg/L，加标回收为95.4%~104.7%，相对标准偏差<6%。运用于实际水样分析显示，无机砷As(III)和As(V)占到总砷的60%~80%，是水中砷的主要存在形态。通过碰撞反应池技术能够有效消除⁴⁰Ar³⁵Cl⁺干扰，建立的校正方程（I_校正=I_实测−0.13I_干扰）显著提升检测准确性。

关键词：高效液相色谱-电感耦合等离子体质谱；形态砷；环境地表水；方法验证；无机砷；响应面法

中图分类号：O65；X832              文献标识码：A              文章编号：0258-3283（2025）--

DOI：10.13822/j.cnki.hxsj.2025.0034

Analysis of Arsenic Species in Environmental Surface Water for RSM by High-Performance Liquid Chromatography-Inductively Coupled Plasma Mass Spectrometry NIU Qian^*，ZHANG Jun-wei (Luoyang Ecological & Environmental Monitoring Center, Luoyang 471000, China)

Abstract: To address the insufficient separation efficiency of traditional detection methods in complex matrices, a novel method was developed by integration response surface methodology (RSM) with high-performance liquid chromatography-inductively coupled plasma mass spectrometry (HPLC-ICP-MS) for the sensitive determination of six arsenic species in environmental surface water: arsenate (As(V)), arsenite (As(III)), monomethylarsonic acid (MMA), dimethylarsinic acid (DMA), arsenobetaine (AsB), and arsenocholine (AsC). A Box-Behnken design was employed to optimize the mobile phase pH (6.0~7.0), methanol ratio (10%~20%), and injection volume (20~40 μL), resulting in a well-fitted quadratic regression model (R² = 0.951). Significant interaction between pH and methanol was observed. The optimal conditions were determined to be pH 6.7, 13% methanol and 28 μL injection, yielding a total resolution of (11.4 ±0.3). Using a Hamilton PRP-X100 column with gradient elution, all six  arsenic species were baseline separated (resolution>1.5) within 12 minutes. Detection limits ranged from 0.06 to 0.17 μg/L, with spike recoveries of 95.4% to 104.7% and relative standard deviations below 6%. Field analysis revealed inorganic arsenic species (As(III)+As(V)) accounted for 60%-80% of total arsenic. Interference from 40Ar35Cl+ was effectively eliminated using collision/reaction cell technology (He flow 4.5 mL/min), and a correction equation (I_corrected = I_measured - 0.13I_interference) significantly enhanced detection accuracy.

Key words：high performace liquid chromatography-inductively coupled plasma mass spectrometry; arsenic species; environmental surface water; method validation; inorganic arsenic; response surface methodology

【分析与测试】

酶联免疫快检技术在合成色素检测中的应用

梁睿丹，马康^*，周澍??/font>

(中国计量科学研究院，北京  100029)

摘要：随着食品安全问题日益成为社会关注的焦点，食品添加剂，尤其是合成色素的使用成为了重要议题。合成色素在提升食品外观吸引力的同时，也可能对人体健康产生潜在危害，如过敏反应、致癌性等。因此，开发高效、灵敏的快速检测技术对于食品安全现场检查是至关重要的。酶联免疫吸附快检技术（ELISA）利用抗原-抗体的特异性结合原理，能够高效、精准地识别和定量分析食品中微量的合成色素。与传统的检测方法相比，ELISA极大地提升了食品安全现场检查的效率。对ELISA在合成色素检测中的应用现状进行了总结，分析了其在不同类型色素检测中的优势与局限性。重点探讨了ELISA在偶氮类色素、三芳基甲烷类色素及氧杂蒽类色素检测中的成功应用，并指出了ELISA在多重检测能力、样品基质效应及操作复杂度等方面的挑战。最后，展望了ELISA未来在食品合成色素检测中的发展方向，强调了技术创新和优化对提升食品安全检测水平的重要性，以及对保障公众健康和提升食品安全水平起到更加重要的作用。

关键词：酶联免疫吸附快检技术；合成色素；偶氮类色素；三芳基甲烷类色素；氧杂蒽类色素

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.2025.0033

Application of ELISA Rapid Test Technology in Synthetic Colorants Detection LIANG Rui-dan, MA Kang^*, ZHOU Shu-kun (National Institute of Metrology, Beijing 100029, China)

Abstract：As food safety increasingly becomes a focus of public concern, the use of food additives, especially synthetic colorants, has become an important issue. Synthetic colorants may not only enhance the visual appeal of food, but also have potential hazards to human health, such as allergic reactions and carcinogenicity. Therefore, the development of highly efficient, sensitive, and rapid test technologies is crucial for food safety. Enzyme-linked immunosorbent assay (ELISA) leverages the specific binding between antigens and antibodies to efficiently and accurately identify and quantify trace amounts of synthetic colorants in food. Compared with traditional detection methods, ELISA significantly improves the efficiency of on-site food safety inspections. This review summarized the current application status of ELISA in synthetic colorant detection, and analyzed its advantages and limitations in the detection of different types of colorants. The successful application of ELISA in detecting azo, triylmethane and oxanthene dyes was discussed, and the challenges of ELISA in multiplex detection capability, sample matrix effect, and operational complexity were highlighted. Finally, the future development direction of ELISA for food synthetic colorants was prospected, and the importance of technological innovation and optimization in enhancing food safety testing, protecting public health, and improving food quality assurance was emphasized.

Key words：enzyme-linked immunosorbent assay; synthetic colorants; azoles dyes; triylmethane dyes; xanthene dyes

高效液相色谱法同时测定布美他尼原料药中8种杂质含量

叶红兵，张蒙蒙，夏宇航，陶俊钰^*

（合肥市食品药品安全检验检测中心  安徽 合肥  230071）

摘要：建立高效液相色谱法（HPLC-DAD）同时检测布美他尼原料药中的8种杂质含量。采用Thermo Hypersil GOLD C18（4.6 mm×250 mm, 5 μm,孔径120 Å）为色谱柱，以0.1%(体积分数)三氟乙酸溶液（取1 mL三氟乙酸溶于1000mL水中）为流动相A ，甲醇为流动相B，梯度洗脱（0～5 min 60%A；5～10 min 60%A→15%A;10～20 min 15%A；20～25 min 15%A→60%A；25～30 min 60%A），流速为1.0 mL/min,柱温为30℃，进样量为20 μL。 空白溶剂不干扰布美他尼及其8种杂质的测定，杂质A、B、C、D、E、G、I、J质量浓度分别在0.0201～4.0280、0.0280～3.7301、0.0458～3.6618、0.0509～4.0692、0.0485～3.8773、0.1011～4.0428、0.0509～4.0700和0.0518～4.1477 μg/mL范围内与相应峰面积呈良好的线性关系，相关系数r分别为0.9993、0.9991、0.9999、0.9994、0.9996、0.9992、0.9999、0.9988，检测限（LOD）为7.05～35.37 ng/mL，定量限（LOQ）为20.14～101.07 ng/mL，杂质A、B、C、D、E、G、I、J的平均回收率分别为95.4%、93.0%、101.1%、98.7%、100.0%、101.0%、101.2%、98.1%，RSD分别为1.26%、0.63%、1.97%、0.40%、3.08%、0.79%、1.18%、0.85%。所建立的高效液相色谱法（HPLC）高效、稳健、准确，可同时测定布美他尼原料药中8种杂质（工艺杂质与降解产物）的含量。

关键词: 高效液相色谱法；布美他尼；工艺杂质；降解产物；含量

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.2025.0053

Simultaneous determination of eight impurities in bumetanide API by HPLC YE Hong-bing, ZHANG Meng-meng, XIA Yu-hang, TAO Jun-yu^* (Hefei Food and Drug Safety Inspection and Testing Center, Hefei 230000, China)

Abstract: A high-performance liquid chromatography method with diode-array detection (HPLC-DAD) was established for the simultaneous determination of eight impurities in bumetanide active pharmaceutical ingredient (API). A Thermo Hypersil GOLD C18 (4.6mm × 250mm, 5 μ m，pore size120 Å) was used, with 0.1% volume fraction trifluoroacetic acid solution (prepared by dissolving 1ml trifluoroacetic acid in 1000ml water) as mobile phase A and methanol as mobile phase B. A gradient elution was employed (0-5min 60% A; 5-10min 60% A → 15% A; 10~20min 15%A; 20~25min 15%A → 60% A; 25～30 min 60%A). The flow rate was 1.0 mL/min, the column temperature was 30℃, and the injection volume was 20μL. The blank solvent showed no interference with the detection of bumetanide or its eight impurities. The mass concentrations of impurities A, B, C, D, E, G, I, and J showed good linear relationships with their corresponding peak areas in the range of 0.0201～4.0280, 0.0280～3.7301, 0.0458～3.6618, 0.0509～4.0692, 0.0485～3.8773, 0.1011～4.0428, 0.0509～4.0700, and 0.0518～4.1477μg/mL, respectively. The correlation coefficients r was 0.9993, 0.9991, 0.9999, 0.9994, 0.9996, 0.9992, 0.9999, and 0.9988. The limits of detection (LOD) ranged from 7.05 to 35.37ng/mL, and the limits of quantification (LOQ) ranged from 20.14 to 101.07ng/mL. The average recoveries of impurities A, B, C, D, E, G, I, and J were 95.4%, 93.0%, 101.1%, 98.7%, 100.0%, 101.0%, 101.2%, and 98.1%, respectively, with corresponding relative standard deviations (RSDs) of 1.26%, 0.63%, 1.97%, 0.40%, 3.08%, 0.79%, 1.18%, and 0.85%. The established HPLC method is efficient, robust and accurate, and is suitable for the simultaneous determination of eight impurities (both process-related impurities and degradation products) in bumetanide API.

Key words: HPLC; bumetanide; process impurities; degradation products; quantitative analysis

高效液相色谱-串联质谱法测定进口人参类化妆品中

皂苷成分含量

赵韫慧^*1, 王嘉怡¹，于淼淼¹，翟亚楠¹，杨璐¹，迟迅²

（1.长春海关技术中心, 吉林 长春，130062; 2. 长春中医药大学 创新实践中心，吉林 长春，130117）

摘 要：针对市面上含有人参成分的进口乳液、膏霜和面膜3种化妆品基质中6种人参皂苷（Rb1、Rb2、Rc、Rd、Re 和 Rg1）成分测定建立快速高效的前处理方法，应用高效液相色谱-串联质谱仪，对进口人参类化妆品中6种人参皂苷成分进行定性和定量分析。建立的测定方法主要在色谱和质谱条件方面进行了优化，提高了检测灵敏度和准确性。样品经乙醇水超声提取，提取液用C18固相萃取柱净化，氮吹复溶后，乙腈-0.1%甲酸水为流动相，应用高效液相色谱-串联质谱仪进行检测，多反应检测模式，负离子模式扫描。经验证，6种人参皂苷在0.2 ~100 µg/L浓度范围内线性关系良好（r>0.9995），方法检出限为0.01~0.06 μg/kg，定量限为0.02~0.5 μg/kg，满足测定需求。对33种空白样品分别加3种浓度（5、10、20 μg/kg，n=6），检测结果相对标准偏差均小于5%，且加标回收率均大于80%。用该方法对进口人参类化妆品中的6种人参皂苷进行定性定量分析，灵敏度高、重现性好，且具有较高的精密度和准确度。可为海关对进口人参类化妆品的监管提供评估数据和技术支持。

关键词：人参类化妆品；皂苷；高效液相色谱-串联质谱；定性；定量；固相萃取柱

中图分类号:O657.31; X832    文献标识码:A     文章编号：0258-3283（2025）--

DOI：10.13822/j.cnki.hxsj.2025.0061

Determination of Ginsenoside Content in Imported Ginseng-Based Cosmetics by HPLC-MS/MS ZHAO Yun-hui^*1, Wang Jia-yi¹, Yu Miao-miao¹, Zhai Ya-nan¹, Yang Lu¹, Chi Xun²（1. Changchun Customs Technology Center, Changchun 130062, China; 2. Innovation Practice Center, Changchun University of Chinese Medicine, Changchun 130117, China）

ABSTRACT： A rapid and efficient pre-treatment was established for determining six ginsenosides (Rb1, Rb2, Rc, Rd, Re and Rg1) in three types of ginseng-containing imported available on the market: emulsions, creams, and facial masks. Qualitative and quantitative analyses of these ginsenosides was carried out using high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS). The developed method was optimized mainly in terms of chromatographic and mass spectrometric conditions to improve the detection sensitivity and accuracy. Samples were extracted by ultrasonic ethanol-water method. The extracted was purified by C18 solid-phase extraction column and reconstituted after nitrogen evaporation. Detection was performed using HPLC-MS/MS with acetonitrile-0.1% formic acid aqueous solution as the mobile phase, under multiple reaction monitoring (MRM) mode and negative ion scanning. After method verification, the six ginsenosides showed good linearity in the concentration range of 0.2 ~100 μg/L (R>0.9995). The detection limit of the method was 0.01~0.06 μg/kg, and the quantification limit was 0.02~0.5 μg/kg, which meets the measurement requirements. Thirty-three blank samples were each spiked at three concentration levels (5, 10, 20 μg/kg, n=6). The relative standard deviations were all below 5% and the spiked recovery rates were all above 80%. This method is used for qualitative and quantitative analysis of six ginsenosides in imported ginseng cosmetics, which offers high sensitivity, good repeatability, high accuracy, and precision. This method can provide assessment data and technical support for the customs supervision for imported ginseng cosmetics.

Key Words: ginseng-based cosmetics; ginsenoside; high performance liquid chromatography tandem mass spectrometry; qualitative analysis; quantitative analysis; solid-phase extraction columns

【合成与应用】

稠合噌啉化合物合成研究进展

黄桢惠，罗小芹，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：噌啉是一类由苯环与哒嗪环稠合而成的双氮杂环化合物，由于其独特的刚性平面结构和显著的生物活性，已成为合成化学、药物研发及功能材料领域的重要研究对象。噌啉结构中苯环与杂环通过共轭作用，取代基效应及能级调控，可显著调节电子云分布，其电子结构特征影响生物活性（抗菌、抗癌）、光电性能（发光效率）及化学反应性（C―H活化选择性）。近年研究表明，该类化合物在抗菌、镇痛、抗炎及抗肿瘤等药理活性方面展现出应用前景，但其复杂稠环共轭体系导致高效合成路线的开发仍是合成化学领域的关键科学问题。基于起始原料的化学特征，以噌啉化合物的合成前体为分类依据，综述了近年来基于偶氮苯/三氮唑、芳基肼/芳酰腙、芳基吡唑酮/吲唑酮等前体化合物的噌啉稠环体系高效构建策略，以期为该领域的深入研究和应用开发提供理论依据与方法学参考。最后，展望了噌啉稠环化合物在药物研发、材料科学等领域的应用前景，分析了目前面临的挑战，并提出了相应的解决策略。

关键词：噌啉；杂环化合物；合成；药理活性；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.2025.0092

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

Abstract：Cinnoline, a class of diazaheterocyclic compounds fused by benzene ring and pyridazine ring, has become an important research object in synthetic chemistry, drug development, and functional materials due to its unique rigid planar structure and notable biological activity. The conjugation between the benzene and heterocyclic rings, combined with substituent effects and energy level modulation, can significantly regulate the electron density distribution. This electronic structure modulates its biological activities (antibacterial, anticancer), photoelectric properties (luminescence efficacy), and chemical reactivity (C?H activation selectivity). Recent studies have demostrated cinnoline derivatives showed promising pharmacological activities , including antibacterial, analgesic, anti-inflammatory, anti-tumor effects. However, the development of efficient synthetic routes for these complex fused ring conjugated systems remains a major challenge in synthetic chemistry. The article categorized cinnoline synthesis strategies based on the chemical characteristics of the starting materials and their corresponding synthetic precursors, including azobenzene/triazole, aryl hydrazine/aroyl hydrazone, and aryl pyrazolone/indazolone. This study systematically summarized advanced strategies for constructing cinnoline fused-ring systems, aiming to provide theoretical basis and methodological references for the in-depth research and application development. Finally, the future application of fused cinnoline compoinds in drug development and functional material were discussed. The current challenges were anayzed, and the corresponding solutions were proposed.

Key words：cinnoline; fused heterocyclic compounds; synthesis; pharmacological activity; research progress

含氮螺环芳酮的合成

张琳婕¹，罗强¹，柯德宏²，许胜^*1

(1. 华东理工大学 化学与分子工程学院，上海  200237；2. 上海沃凯生物技术有限公司，上海  201506)

摘要：α-氮杂螺环是一类重要的有机配体，因其氮原子具有亲核性且该类化合物具有独特的空间结构，常用于螺手性金属有机化合物的有机配体，也是一种重要的药物合成中间体；另一方面，羰基是一个潜在的有机官能团转换母体，可以通过亲核加成反应将底物转化为具有潜在配位功能的有机配体，如和H₂NG反应得到席夫碱、肟、腙和缩氨脲，和HCN加成得到α-羟基腈，与环戊二烯金属盐反应得到富烯进而作为茂金属配体等。在螺原子的α，α’-位置分别引入羰基和胺基，形成含氮螺环芳酮化合物，作为手性螺环化合物配体，为螺手性催化剂的合成提供了重要的技术支持。以芳酮为原料，经过肟基引入、还原、环化、脱乙酰基4步反应，高收率得到了一系列新型含氮螺环芳酮化合物，所有产物都通过¹HNMR、¹³CNMR、HRMS进行了表征，确认了其结构，并通过单晶X-ray衍射确认了其空间结构，受氮原子影响，含氮杂环为空间上扭曲的不规则的五边形。研究结果表明，此合成方法具有工艺简单、产品收率高、产物对热稳定等优点。

关键词：合成；螺环；含氮；芳香酮；合成工艺

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.2025.0098

Synthesis of Nitrogen-Containing Spiro Aromatic Ketones ZHANG Lin-Jie ¹，LUO Qiang¹，KE De-hong²，XU Sheng^*1 (1. School of Chemistry and Molecular Engineering，East China University of Science and Technology，Shanghai 200237，China; 2. Shanghai Our ChemBio-Technology Co., Ltd., Shanghai 201506, China)

Abstract：α-Azaspiro rings are a class of important organic ligands, because of the nucleophilic nitrogen atoms and the unique spatial structure of these compounds, often used as organic ligands for spirochiral metal-organic compounds. Actually, they are important intermediates in the synthesis of drugs. On the other hand, carbonyl is a potential organic functional group conversion precursor that can be converted into organic ligands with potential coordination functions through nucleophilic addition reactions, such as Schiff bases, oximes, hydrazones, and semicarbazides obtained by reacting with H₂NG, and α - hydroxynitriles obtained by adding with HCN, reaction with cyclopentadienyl metal salt to obtain fulvene, which then serves as a metallocene ligand, etc. Carbonyl and amino groups at the α, α '- positions of the spiro atom were introduced to form nitrogen-containing spirocyclic aromatic ketone compounds, which serve as chiral spiro ligands and provide important technical support for the synthesis of spiro chiral catalysts. Aromatic ketones was used as raw materials, a series of novel nitrogen-containing spirocyclic aromatic ketone compounds were obtained in high yield through four steps of oxime introduction, reduction, cyclization, and deacetylation. All these products were well characterized by ¹HNMR, ¹³CNMR, and HRMS to confirm their structures. The spatial structure of P5 was confirmed by single-crystal X-ray diffraction, and the nitrogen-containing heterocycles were spatially distorted irregular pentagons influenced by nitrogen atoms. The research results indicate that the method proposed in this article has the advantages of simple process, high product yield, and thermal stability of the product.

Key words：synthesis; spiral ring; nitrogen-containing; aromatic ketone; synthesis process