四川大学化学学院
师资力量

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

个人主页:点击进入

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 化学学院 硕、博士

2008.7- 2011.6 四川大学 化学学院 讲师

2010.11-2011.10 香港大学 化学学院 博士后

2011.7-2016.8 四川大学 化学学院 副教授

2016.9-至今  四川大学  化学学院 教授

2018. 7 四川大学化学学院 博士生导师

主要研究方向:

化学生物学:反应型荧光探针的设计、合成及在生命体内的应用研究

在研科研项目:

1. 国家重点研发计划课题一,(绿色生物制造)(2021YFC2102001),生物催化的手性形成机制解析,431万,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

3. 四川省杰出青年科技基金(2020JDJQ0017):修饰核酸的检测及测序分析,项目负责人,2020.01-2022.12

科研奖励:

1. 基于联萘酚结构的荧光探针,2019年四川省科技进步奖(自然科学类)二等奖(3/3

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。

近年代表性成果:

1. 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

2. 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.

3. 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.

4. 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.

5. 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.* Rapid and ultrasensitive imaging of plasma membrane with AIE based probe in bio-systems Angew. Chem. Int. Ed. 2020, 59, 9962-9966.

6. 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.

7. 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.

8. 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.

9. 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.

10. 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.

11. Shi, L.; Li, K.*; Li, L.-L.; Chen, S. Y.; Li, M.-Y.; Zhou, Q.; Wang, N.; Yu, X.-Q.* Novel easily available purine-based AIEgens with colour tunability and applications in lipid droplet imaging. Chem. Sci. 2018, 9, 8969-8974.

12. Zhou, Q.; Li, K.*; Liu, Y.-H.; Li, L.-L.; Yu, K.-K; Zhang, H.; Yu, X.-Q.* Fluorescent Wittig reagent as a novel ratiometric probe for the quantification of 5-formyluracil and its application in cell imaging. Chem. Commun. 2018, 54, 13722-13725

13. Li, L.-L,; Li, K.*; Li, M.-Y.; Shi, L.; Liu, Y.-H.; Zhang, H.; Pan, S.-L.; Wang, N.; Zhou, Q.; Yu, X.-Q,* BODIPY-Based Two-Photon Fluorescent Probe for Real-Time Monitoring of Lysosomal Viscosity with Fluorescence Lifetime Imaging Microscopy. Anal. Chem. 2018, 90, 5893-5878.

14. Pan, S.-L.; Li, K.*; Li, L.-L.; Li, M.-Y.; Shi, L.; Liu, Y.-H.; Yu, X.-Q.* A reaction-based ratiometric fluorescent sensor for the detection of Hg(II) ions in both cells and bacteria. Chem. Commun. 2018, 54, 4955-4958.

15. Yang J.; Li, K.*; Hou, J.-T.; Lu C.-Y.; Li, L.-L.; Yu, K.-K.; Yu, X.-Q.* A novel coumarin-based water-soluble fluorescent probe for endogenously generated SO2 in living cells. Sci China Chem, 2017, 60: 793–798.

16. Li, K.#; Hou, J.-T.#; Yang, J.; Yu, X.-Q.* A tumor-specific and mitochondria-targeted fluorescent probe for real-time sensing of hypochlorite in living cells. Chem. Commun. 2017, 53, 5539-5541.

17. Hou, J.-T,#; Ren, W.-X.#; Li, K.#; Seo, J.; Sharma, A.; Yu, X.-Q.*; Kim, J.-S.*, “Fluorescent bioimaging of pH: from design to applications” Chem. Soc. Rev. 2017, 46, 2076-2090.

18. Yu, K.-K; Li, K.*; Qin, H.-H.; Zhou, Q.; Qian, C.-H..; Liu, Y.-H.; Yu, X.-Q,* “Construction of pH-sensitive “Submarine” based on gold nanoparticles with double insurance for intracellular pH mapping, quantifying of whole cells and in vivo applications” ACS Appl. Mater. Interfaces 2016, 8, 22839−22848.

19. Yang, J.; Li, K.* ; Hou, J.-T.; Li, L.-L.; Lu, C.-Y.; Xie, Y.-M.: Wang, X.; Yu, X.-Q, * “Novel Tumor-Specific and Mitochondria-Targeted near-Infrared-Emission Fluorescent Probe for SO2 Derivatives in Living Cells”, ACS Sens., 2016, 1, 166-172.

20. Wu, M.-Y.; Li, K.*; Liu, Y.-H.; Yu, K.-K.; Xie, Y.-M..; Zhou, X.-D.*; Yu, X.-Q.* “Mitochondria-targeted ratiometric fluorescent probe for real time monitoring pH in living cells” Biomaterials 2015, 53, 669-678.

专利:

1. 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, ZL202011023009.6202231

2. 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, ZL202011022995.320211022

3. 李坤,石磊,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

4. 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,ZL201910079972.720201229 

5. 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.X20201118

6. 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, ZL201910079970.8202027

7. 余孝其,李坤,周倩,基于香豆素骨架的Wittig 额制备方法及其用途, ZL201810035548.82020728

8. 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

9. 余孝其, 李坤, 杨晋, 取代的香豆素-吡啶衍生物及其制备方法和用途。ZL201510618120.22017426

10. 余孝其, 李坤,徐浩然,取代的香豆素-噻唑橙衍生物及其制备方法和用途 ZL201510852034.8201632

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