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

主要工作业绩

科研项目：

1. 国家自然科学基金面上项目（21572147），DNA动态甲基化过程中5-醛基胞嘧啶选择性反应型小分子荧光探针研究，项目负责人，2016.1-2019.12

2. 四川大学优秀青年学者基金（2013SCU04A41）：DNA甲基化过程中胞嘧啶类衍生物的选择性识别，项目负责人，2013.10-2016.12

3. 国家自然科学基金青年项目（21001077），“自活化”序列选择性人工核酸酶的设计合成及应用研究，项目负责人，2011.1-2013.12。

主要工作业绩及奖励：

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活性氧（ROS）活性硫（RSS）和活性氮（RNS）等信号转导分子的荧光探针，实现了快速、高选择及定量细胞内H2S， SO2， ClO-及ONOO-等活性物质的检测。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, Chem. Commun.,等杂志上共发表SCI收录学术论文70余篇，他引2000余次，获准国家发明专利5项。

代表性成果 (获奖成果、专著、论文、专利)

近五年代表性成果：

1. Shi, L.; Liu, Y.-H.; Li, K.*;   Amit, S.; Yu, K.-K; Ji, M. S.; Li, L.-L.; Zhou, Q.; Zhang, H.; Kim， J.   S.*; Yu, X.-Q.* Rapid and ultrasensitive imaging of plasma membrane with AIE   based probe in bio-systems Angew. Chem. Int. Ed. 2019,   10.1002/anie.201909498.

2. 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.

3. 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.

4. 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.

5. 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.

6. Li, L.-L.; He, P.-Y.; Shi, L.; Pan,   S.-L; Li, M.-Y.; Zhou, Q.; Zhang H.; Wang, N.; Li, K,*; Yu,   X.-Q.* A near-infrared water-soluble   fluorescent probe for the detection of biothiols in living cells and Escherichia   coli. Anal. Methods 2019, 11, 821-826.

7. Qin, H.-H.; Li, L.-L.; Li, K.*;   Yu, X.-Q.* Novel strategy of constructing fluorescent probe for MAO-B via   cascade reaction and its application in imaging MAO-B in human astrocyte. Chin.   Chem. Lett. 2019, 30, 71-74.

8. 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.

9. Shi, L.; Li, K.*; Cui,   P.-C.; Li, L.-L.; Pan, S.-L.; Li, M.-Y.; Yu, X.-Q.* BINOL Derivatives   with Aggression-induced Emission J. Mater. Chem. B 2018, 6(27),   4413-4416.

10. 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

11. Li,   M.-Y.; Cui, P.; Li, K.*; Feng, J.; Zou, M.; Yu, X.-Q.* Dual-site   fluorescent probe for highly selective and sensitive detection of sulfite and   biothiols. Chin. Chem. Lett. 2018, 29(6), 992-994

12. 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.

13. 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.

14. 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.

15. 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.

16. 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.

17. 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.

18. Li, L.-L.; Li, K.*;   Liu, Y.-H.; Xu, H.-R. Yu, X.-Q.* “Red emission fluorescent probes for   visualization of monoamine oxidase in living cells”. Sci. Rep. 2016,   6, 31217.

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. Liu, Y.; Li, K.*; Xie,   K.-X.; Li, L.-L.; Yu, K.-K.; Wang, X.; Yu, X.-Q.* “A water-soluble and   fast-response mitochondria-targeted fluorescent probe for colorimetric and   ratiometric sensing of endogenously generated SO₂ derivatives in   living cells”, Chem. Commun. 2016, 52, 3430-3433.

21. Chen, X.-L.; Chen, H.; Lu, C.-Y.; Yang,   C.; Yu, X.-Q.; Li, K.*; Xie. Y.* “Novel mitochondria-targeted,   nitrogen mustard-based DNA alkylation agents with near infrared fluorescence   emission” Talanta, 2016, 161, 888-893.

22. Ran, Y.-Z.; Xu, H.-R.; Li, K.*;   Yu, K.-K.; Yang, J.; Yu, X.-Q.* “Development of a mitochondria-targeted   fluorescent probe for hydrazine monitoring in living cells” RSC Adv. 2016,   6, 111016-111019.

23. Liao, Y.-X.; Yang, Z.-X.; Li, K.*;   Yu, X.-Q.* “A highly selective ratiometric fluorescent probe for   peroxynitrite detection in aqueous media” Chem. Lett. 2016, 45(6),   691-693.

24. 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.

25. Liu, Y.; Li, K.*; Wu,   M.-Y.; Liu, Y. -H.; Xie, Y.-M*; Yu, X.-Q.* “A Mitochondria-targeted   Colorimetric and Ratiometric Fluorescent Probe for Biological SO₂ Derivatives   in Living Cells” Chem. Commun. 2015, 51,10236-10239.

26. Hou, J.-T.; Li, K.*; Yang,   J.; Yu, K.-K.; Liao, Y.-X.; Ran, Y.-Z.; Liu, Y.-H., Zhou, X. D.*; Yu, X.-Q.*   “A ratiometric fluorescent probe for in situ quantification of basal   mitochondrial hypochlorite in cancer cells.” Chem. Commun. 2015, 51, 6781-6784.

27. Yu, K.-K; Hou, J.-T.; Li, K.*;   Yao, Q.; Yang, J.; Wu, M.-Y, Xie, Y.-M.: Yu, X.-Q, * “A single design   strategy for dual sensitive pH probe with a suitable range to map pH in   living cells” Sci. Rep. 2015, 5, 15540

28. Jiao, S.-Y.; Li, K.*;   Zhang, W.; Liu, Y.-H.; Huang, Z.; Yu, X.-Q.* “Cd(II)- terpyridine-based   complex as a ratiometric fluorescent probe for pyrophosphate detection in   solution and as an imaging agent in living cells.” Dalton Trans., 2015, 44,   1358-1365.

29. Jiao, S.-Y.; Li K.* Wang,   X.; Huang, Z.; Pu, L.; Yu, X.-Q.* “Making pyrophosphate visible: the first   precipitable and real-time fluorescent sensor for pyrophosphate in aqueous   solution.” Analyst, 2015, 140, 174–181.

30. Hou, J.-T.; Yang, J.; Li, K.*;   Yu, K.-K.; Yu, X.-Q.* “A colorimetric and red emissive fluorescent probe for   cysteine and its application in bioimaging.” Sensor Actuat. B: Chem.,   2015, 214, 92-100.

31. Liao, Y.-X.; Wang, M.-D.; Li, K,*;   Yang, Z.-X.; Hou, J.-T.; Wu, M.-Y.; Liu, Y.-H.; Yu, X. Q.* “A highly sensitive and selective “turn-on” fluorescent probe   for hypochlorous acid monitoring” RSC Adv., 2015, 5,   18275-18278.

32. Xu, H.-R.; Li, K.*; Jiao,   S.-Y.; Pan, S.-L.; Zeng, J.-R.; Yu, X.-Q.* “Tetraphenylethene– pyridine salts   as the first self-assembling chemosensor for pyrophosphate” Analyst, 2015,   140, 4182-4188.

33. Xu, H.-R.; Li, K.*; Jiao,   S.-Y.; Li, L.-L.; Pan, S.-L.; Yu, X.-Q.* Tetraphenylethene based zinc   complexes as fluorescent chemosensors for pyrophosphate sensing”, Chin.   Chem. Lett. 2015, 26, 877-880.

34. Xu, B.-Y.; Hou, J.-T.; Li, K.*;   Lu, Z.-W.; Yu, X.-Q.* A BINOL Based Fluorescence Sensor for Distinction of   D-Glucose. Chin. J. Chem. 2015, 33(1), 101-106.

专利：

1. 余孝其，李坤，吴明雨，王娜，一种合成4-芳基-4，5-二氢呋喃类衍生物的新方法。专利号：ZL   201010160246.7

2. 余孝其，李坤，后际挺，取代的水杨醛-TCF衍生物及其制备方法和用途。 专利号: ZL201410023272.3

3. 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。专利号：ZL201510618120.2

4. 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 CN201510852034

5. 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 CN201510618052