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李坤     教 授

研究方向:化学生物学、有机化学

联系方式:028-85418580          Email:kli@scu.edu.cn

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学习及工作简历:

1999.9-2003.7 烟台大学 化学生物理工学院  学士

2003.9-2008.6 四川大学 bwin必赢 硕、博士

2008.7- 2011.6 四川大学 bwin必赢 讲师

2010.11-2011.10 香港大学 bwin必赢 博士后

2011.7-2016.8 四川大学 bwin必赢 副教授

2016.9-至今  四川大学  bwin必赢 教授

2018. 7 bwin必赢 博士生导师

主要研究方向:

主要从事荧光染料的构建及在细胞成像、荧光手术导航等方面的应用研究。先后主持国家重点研发计划课题、国家自然科学基金面上基金及四川省杰出青年科技人才基金在内的国家和省部级项目6项,在Adv. Mater., Angew. Chem. Int. Ed. 等杂志上发表学术论文90多篇,他引5000多次,获准国家发明专利15项。获得四川省科技进步奖(自然科学类)二等奖1项(排名第三),广东省科技进步奖二等奖1项(排名第四)。现担任中国化工学会精细化工专业委员会委员、中国感光学会-光学传感与诊疗专业委员会委员。

科研项目:

1. 国家重点研发计划课题,(绿色生物制造)(2021YFC2102001),生物催化的手性形成机制解析,课题负责人,2021.07-2025.06

2. 国家自然科学基金面上项目(22077088),醛基腺嘌呤的选择性检测及测序分析,项目负责人,2021.01-2024.12

科研奖励:

1. 基于联萘酚结构的荧光探针,四川省科技进步奖(自然科学类)二等奖(20193/3

2. 龋源性牙髓根尖周病微创诊疗新体系的建立与应用,广东省科技进步奖二等奖,(20224/10

主要工作业绩:

开展以细胞内相关活性物质为导向的荧光分子探针的设计合成及其应用研究。设计合成了一系列基于细胞内信号转导分子、功能性酶及特异性核酸的荧光探针,实现了细胞内活性氧(ROS)、活性硫(RSS)等活性物质的快速、高选择及定量检测。开发了一类全新的以天然碱基为骨架的AIE荧光染料分子,并实现了其在活细胞内脂滴的靶向成像;在此基础上,构建了细胞膜靶向的分子荧光探针,具有快速、免洗及长效追踪细胞膜成像的特点。在核酸检测方面,我们首次将Wittig试剂引入到修饰碱基5-醛基胞嘧啶和5-醛基尿嘧啶的特异性识别及定量检测中,通过光辅助的串联反应,对两者进行区分,并可实现单碱基分辨率测序。已在Angew. Chem. Int. Ed., Chem. Sci., Biomaterials 等杂志上共发表SCI收录学术论文70余篇,他引3000余次,获准国家发明专利10项。

近五年发表论文:

1. Xiang, F.-F.; Zhang, H.; Wu, Y.-L.; Chen, Y.-J.; Liu, Y. Z.; Chen, S.-Y.; Guo, Y.-Z.; Yu, X.-Q.; Li, K.* Machine Learning-assisted Rational Design of Si-rhodamine as Cathepsin-pH Activated Probe for Accurate Fluorescence Navigation. Adv. Mater. 2024, 2404828

2. Ding, R.-L.; Liu, X.; Zhang, W.-J.; Chen, X.; Chen, S.-Y.; Yu, X.-Q; Zhao, Z.-H*; Li, K.* Purine-Based Ir(III) Photosensitizers for Efficient Treatment of Periodontal Inflammation, Adv. Funct. Mater. 2024, 2405499

3. Chen, X.; Shi, L.; Ran, X.-Y.; Xu, J.-X.; Zhang, L.-N.; Kong, Q. -Q; Yu, X.-Q.; Li, K.* Molecular Engineering of D-𝝅-A Conjugate with N-Heterocycle Purine for Enhanced ROS Generation and Photodynamic Therapy, Adv. Funct. Mater. 2024, 2400728.

4. Chen, X.; Shi, L.; Ran, X.-Y.; Zhang, L.-N.; Xie, K.-P.; Zhao Y.; Chen, J.; Ye, L.; Yu, X.-Q.; Li, K.* Rational Design of an Intramolecular Hydrogen Bond Enhanced Fluorescent Probe for Diagnosis of Drug-Induced Liver Injury, ACS Materials Lett. 2024, 6, 1059-1068.

5. Li, J.-M.; Xiang, F.-F.; Zhou, D.-H.; Xu, J.-X.; Zhang, H.; Liu, Y.-Z.; Kong, Q.-Q.; Yu, X.-Q.; Li, K.* Rational Design of Near-Infrared Fluorescent Probes for AccuratelyTracking Lysosomal Viscosity with Allyl Anchoring Si-Rhodamine, Chem. Biomed. Imag. 2024, 2, 126-134.

6. Liang, J.; Ran, X.; Liu, Y.; Yu, X.-Q.; Chen, S.-Y.* and Li, K.* Rational design of type-I photosensitizer molecules for mitochondrion-targeted photodynamic therapy, J. Mater. Chem. B, 2024, 12, 3686-3693.

7. Ran, X.-Y.; Chen, P.; Liu, Y.-Z.; Shi, L.; Chen, X.; Liu, Y.-H.; Zhang, H.; Zhang, L.-N.; Li, K.*; Yu, X.-Q., Rational Design of Polymethine Dyes with NIR-II Emission and High Photothermal Conversion Efficiency for Multimodal Imaging-Guided Photo-immunotherapy, Adv. Mater. 2023, 2210179

8. Liu, Y.Z.; Ran, X.-Y.; Zhou, D.-H.; Zhang, H.; Chen, Y.-J.; Xu, J.-X.; Chen, S.-Y.; Kong, Q.-Q.; Yu, X.-Q.; Li, K.* Novel Dibenzofulvene-Based NIR-II Emission Phototheranostic Agent with an 82.6% Photothermal Conversion Efficiency for Photothermal Therapy. Adv. Funct. Mater. 2023, 2311365.

9. Zhang, H.; Xiang, F.-F.; Liu, Y.-Z.; Chen, Y.-J.; Zhou, D.-H.; Liu, Y.-H.; Chen, S.-Y.; Yu X.-Q.; Li, K.* Molecular Engineering of Sulfone-Xanthone Chromophore for Enhanced Fluorescence Navigation, JACS Au, 2023, 3, 34623472

10. Chen, Y.-J.; Zhang, H.; Liu, Y.-Z.; Shi, L.; Xiang, F.-F.; Lin, R.-D.; Liu, Y.-H.; Chen, S.-Y.; Yu, X.-Q.; Li, K.*, Rational Design of pH-Independent and High-Fidelity Near-Infrared Tunable Fluorescent Probes for Tracking Leucine Aminopeptidase In Vivo; ACS Sen. 2023, 8, 2359-2367.

11. Liu, Y.-Z.; Zhang, H.; Zhou, D.-H.; Liu, Y.-H.; Ran, X.-Y.; Xiang, F.-F.; Zhang, L.-N.; Chen, Y.-J.; Yu, X.-Q.; Li, K.*, Migration from Lysosome to Nucleus: Monitoring Lysosomal Alkalization-Related Biological Processes with an Aminofluorene-Based Probe. Anal. Chem. 2023, 95, 7294-7302.

12. Zhang, L.-N.; Zhang, H.; Chen, S.-Y.*; Liu, Y.-Z.; Yang, X.-H.; Xiang, F.-F.; Liu, Y.-H.; Li, K.*; Yu, X.-Q., γ-Glutamyltranspeptidase and pH based ‘‘AND’’ logic gate fluorescent probe for orthotopic breast tumor imaging, Chem. Commun. 2023, 59, 2795-2798.

13. Li, N.; Zhou, Q.; Li, K.*; Jiang, T.; Yu, X.-Q.* Qualitative and quantitative detection of aldehydes in DNA with 2-amino benzamidoxime derivative. Chin. Chem. Lett. 2023, 34, 107471.

14. Zhang, H.; Shi, L.; Li, K.*; Liu, X. Won, M.; Liu, Y.-Z.; Choe, Y.; Liu, X.-Y.; Liu, Y.-H.; Chen, S.-Y.; Yu, K.-K.; Kim, J.-S.*; Yu X.-Q.* Discovery of an Ultra-rapid and Sensitive Lysosomal Fluorescence Lipophagy Process. Angew. Chem. Int. Ed. 2022, e202116439

15. Zhang, H.#; Li, L.-L.#; Shi, L.; Chen, S.-Y.; Li, K.*; Yu, X.-Q.*, AnAND-based ratiometric fluorescence probe for the sequential detection of biothiols and hypochlorous acid Chem. Commun. 2022, 58, 13720-13723.

16. Chen, S.-Y.; Li, Z.; Li, K.*; Yu, X.-Q.* Small molecular fluorescent probes for the detection of lead, cadmium and mercury ions. Coordin. Chem. Rev.  2021, 429, 213691.

17. Liu, X.; Li, K.*; Shi, L.; Zhang, H.; Liu, Y.-H.; Wang, H.-Y.; Wang, N.; Yu, X.-Q.* Purine-based Ir(iii) complexes for sensing viscosity of endo-plasmic reticulum with fluorescence lifetime imaging microscopy. Chem. Commun. 2021, 57, 2265-2268.

18. Zhou, Q.; Li, K.*; Yu, K.-K.; Li, N.; Shi, L.; Chen, H; Chen, S.-Y.; Yu X.-Q.* Aqueous Wittig Reaction-mediated Fast Fluorogenic Identification and Single-base Resolution Analysis of 5-Formylcytosine in DNA. Chem. Commun. 2020, 56, 12158-12161.

19. Shi, L.; Liu, Y.-H.; Li, K.*; Amit, S.; Yu, K.-K; Ji, M. S.; Li, L.-L.; Zhou, Q.; Zhang, H.; KimJ. S.*; Yu, X.-Q.* An AIE-Based Probe for Rapid and ultrasensitive imaging of plasma membrane with AIE based probe in bio-systems Angew. Chem. Int. Ed. 2020, 59, 9962-9966.

20. Shi, L.; Li, K.*; Liu, Y.-H.; Liu, X.; Zhou, Q.; Chen, S.-Y.; Yu, X.-Q.* Bio-inspired assembly in a phospholipid bilayer: effective regulation of electrostatic and hydrophobic interactions for plasma membrane specific probes. Chem. Commun. 2020, 56, 3661-3664.

21. Li, M.-Y.; Li, K.*; Liu, Y.-H.; Zhang, H.; Yu, K.-K; Liu, X.; Yu, X.-Q.* Mitochondria- Immobilized Fluorescent Probe for the Detection of Hypochlorite in Living Cells, Tissues, and Zebrafishes Anal. Chem. 2020, 92, 3262-3269.

22. Li, K.; Li, L.-L.; Zhou, Q.; Yu, K.-K.; Kim, J. S.*; Yu, X.-Q.* Reaction-based fluorescent probes for SO2 derivatives and their biological applications. Coordin. Chem. Rev. 2019, 388, 310-333.

23. Zhou, Q.; Li, K.*; Li, L.-L.; Yu, K.-K; Zhang, H.; Shi, L.; Chen, H.; Yu, X.-Q.* Combining wittig olefination with photoassisted domino reaction to distinguish 5-formylcytosine from 5-formyluracil. Anal. Chem. 2019, 91, 9366-9370.

24. Zhang H.; Li, K.*; Li, L.-L.; Yu, K.-K; Liu, X.-Y.; Li, M.-Y.; Wang, N.; Liu, Y.-H. Yu, X.-Q.*, Pyridine-Si-xanthene: A novel near-infrared fluorescent platform for biological imaging. Chin. Chem. Lett. 2019, 5, 1063-1066.

25. Li, L.-L.; Xu, H.-R.; Li, K,*; Yang, Q.; Pan, S.-L; Yu, X.-Q.* Mitochondrial G-quadruplex targeting probe with near-infrared fluorescence emission. Sensor Actuat. B: Chem., 2019, 286, 575-582.

已授权专利:

1. 李坤,张宏,刘艳红,余孝其 基于碳原子的罗丹明衍生物骨架的溶酶体靶向染色试剂及其制备方法和应用 ZL202011023013.2 2023922

2. 李坤,刘艳昭,陈善勇,余孝其 基于氨基芴骨架的快速及长时间溶酶体或细胞核靶向的近红外染色试剂及其制备方法和应用, ZL202111115590.9 2022422

3. 李坤,张宏,刘艳红,余孝其 硅基罗丹明荧光染色试剂及其制备方法和应用, ZL202011023009.6 202231

4. 李坤,张宏,陈善勇,余孝其 基于磷原子取代罗丹明衍生物骨架的染色试剂及其制备方法和应用, ZL202011022995.3 20211022

5. 李坤,石磊,于抗抗,刘艳红,余孝其, 基于嘌呤骨架的聚集诱导型脂滴靶向染色试剂及其制备方法和应用,ZL202010347324.8, 202154

6. 李坤,周倩,余孝其,衍生醛基嘧啶的方法、检测5-醛基胞嘧啶的方法以及醛基嘧啶衍生物的应用,ZL201910079972.7 20201229

7. 李坤、王楠、于抗抗、余孝其, 基于香豆素骨架的抗菌水凝胶及其制备方法和应用,ZL202010290097.X 20201118

8. 余孝其,李坤,周倩,基于香豆素骨架的Wittig 试剂制备方法及其用途, ZL201810035548.8 2020728

9. 李坤,石磊,余孝其,刘艳红,于抗抗,基于嘌呤骨架的免洗类聚集诱导型细胞膜靶向染色试剂及其制备方法和用途, ZL201910079970.8 202027

10. 余孝其, 李坤,刘雨,  取代的咔唑-吲哚磺酸盐衍生物及其制备方法和用途 ZL201510618052.X20181116

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