学习工作经历：

学术奖励：

研究方向与学生培养：

本课题组以物理有机和有机合成为基础，设计合成具有特殊功能的荧光染料，并进一步开展药学相关研究，具体工作涵盖药化、药理、药剂、药物化学生物学等方面的研究。

1. 染料化学生物学

        a) 荧光分子探针的设计开发；

        b) 生物活性分子的控制释放。

2. 染料药物化学

        a) 氧化还原疾病的防诊治；

        b) 临床耐药菌的药物发现。

过三年或五年的培养，学生在分子设计（物理有机化学）、分子合成（有机化学）、光谱测试分析（紫外可见吸收光谱、稳态与瞬态荧光光谱等）、生物显微成像（共聚焦显微成像、超分辨成像技术）、化学生物学（活性分子控制释放、荧光生物标记、药物先导化合物发现）等方面有较好的培训。

成果发表在Nat. Comm.、JACS、Angew. Chem. Int. Ed.、PNAS、Free Radic. Biol. Med.、Anal. Chem.、Org. Lett.、Chem. Comm.、J. Org. Chem.、Sens. Actuactors B Chem. 等本领域高影响期刊。

正在开展的一些研究包括：

1. 染料化学：

本方向的研究主要关注如下三个方面：1）发展新的染料合成方法；2）设计新的荧光染料母核；3）开发新的功能染料分子。

染料能够吸收可见光，带来颜色。从早期的无机矿物颜料、到天然来源的植物染料、到近现代的各类人工合成染料，颜色的运用及染料的发展可以说是人类文明程度的一个重要标志物。

自William Perkin于1856年意外发现苯胺紫并开启人工合成染料时代以来，种类繁多、结构各异的染料见诸于世，包括偶氮染料、蒽醌染料、呫吨染料、花菁染料、酞菁染料、氟硼吡咯染料、方酸染料等。领域中还有大量重要、但未从结构角度单独分类命名的染料。在此不一一罗列。早期，染料开发主要是为了满足印染、印刷、油漆和涂料等传统领域的需求。随着染料结构的丰富与性质研究的深入，后来应用领域大大拓宽。染料用于生物染色，促成了染色体的发现，开启生物组织学(histology)；用于治疗梅毒，发现抗药物洒尔氟散，开启化学治疗(chemotherapy)的先河；用于治疗细菌感染，发现百浪多息，开启抗生素时代（the Antibiotic Era）。染料还被用于胶片感光、疾病诊断、有机光电材料、激光器、信息存储、防伪打印、生物成像等领域。应用领域不同，染料结构也常需做必要的修饰。这常常需要染料合成方法的创新。

本课题组针对呫吨这样一类染料做了大量的工作，提出了系列全新的合成思路。这些新方法又反过来支持了本课题组在新染料发现方面的努力，促成了EC系列染料的开发。新染料的开发又为进一步的应用研究打下基础。

2. 化学生物学；

本方向的研究主要是面向化学生物学基础研究与生物医学转化研究，开发如下三类小分子化学工具：1）荧光分子探针；2）活性分子光控释放；3）生物氧化剂的淬灭剂。

细胞内有大量内源性的氧化剂，它们参与细胞能量代谢，调控血管舒张、传导神经信号、参与免疫反应。为了避免氧化损伤细胞组分，细胞内有大量还原性物质，包括谷胱甘肽、抗坏血酸、维生素E、硫氧还原酶、谷胱甘肽还原酶等，用以缓冲氧化压力或者修复氧化损伤。这样一个精密调控的、动态的、氧化还原平衡网络对于细胞及组织的健康其关键作用。当细胞内氧化还原失衡，会导致细胞组分的氧化损伤。氧化损伤的长期积累，是各类退行性疾病，包括神经退行性疾病、心血管病、自免疫疾病的病理基础。

对细胞内的氧化还原网络中的关键节点，开发不同的小分子化学工具，可用于研究其在疾病的参与机制，进而可对疾病的预防、诊断和治疗提供新思路。

我们提出了“染料共价组装”高灵敏分子探针设计思路，并进一步开发了系列分子探针。该思路还成功用于其它一些非氧化还原相关的底物如神经毒剂、甲基汞等的探针设计。

我们提出光控、光计量的药物释放机制。光控可以对释放进行时空操控，光计量是指在活性分子释放的同时伴随一个荧光增强，便于利用显微成像技术对释放的位点、速度等进行实时影像跟踪。

同时，我们还在尝试开发一些具有高生物兼容性的还原性物质，用于清除生物氧化剂，对于疾病的预防或治疗有潜在价值。

3. 药物化学；

本方向的研究内容主要涉及到基于染料的新型抗菌化合物的发现。

人类的抗生素时代始于上世纪三十年代，标志性事件是杜马克从偶氮染料中发现百浪多息并治愈其女儿的败血病。同时期，弗莱明与瓦瑟曼分别发现了青霉素和链霉素。之后二十年间，近二十大类结构不同、机制各异的抗生素被发现，进一步通过半合成修饰衍生出数千种抗生素药物。抗生素挽救了大量伤病患的生命，大幅增加人口平均寿命，因此被誉为医学史上最伟大的发明。

进入上世纪80年代，新抗生素发现难度加大，抗生素开发利润降低，再加上人类的盲目乐观，大药企纷纷缩减或裁撤抗菌研究部门，抗生素药物开发几近停滞。在过去三十年，仅有两类新抗生素获FDA批准上市，分别是利萘唑胺和达托霉素。

由于抗生素在临床及养殖业的滥用及无序排放，细菌对临床上各类抗生素逐渐产生产生耐药性。近年来，具有多重耐药性、甚至泛耐药性的超级细菌不断出现，如耐碳青霉烯酶肺炎克雷伯菌、耐碳青霉烯酶鲍曼不动杆菌、耐甲氧西林金黄色葡萄球菌、抗万古霉素肠球菌、耐多药肺炎链球菌、多重抗药性结核杆菌以及铜绿假单孢菌等。当前，全球每年约70万人死于耐药菌导致的感染。领域迫切需要加快高活性抗菌先导化合物的发现及相关药物开发，否则后抗生素时代的来临将不是危言耸听！届时，专家估计，每年可能会有超1000万人死于细菌感染。

针对细菌抗药性这一全球重大公共卫生安全问题，世界卫生组织（WHO）于2016年通过题为《抗微生物药物耐药性问题》的政治宣言。同年，美国签署《21世纪治疗法案》，鼓励抗生素类药物开发。我国亦于今年发布《遏制细菌耐药国家行动计划》，要求严格规范抗生素在临床和养殖业的使用，延缓细菌耐药性的获得，同时通过政策引导与经费支持鼓励药企和高校加快新型抗生素的开发。

论文发表：

38. Yansheng Xiao, Yunxia Huang, Zhenhua Zeng, Xiao Luo,*, Xuhong Qian, Youjun Yang.* “Harnessing Thorpe-Ingold Dialkylation to Access High Hill-percentage pH Probes.” Submitted.

37. Yinghua Guo, Xinru Wang, Yan Feng, Xiao Luo, Xiangming Meng*, Xuhong Qian, Youjun Yang.* “Imaging of Lysosomal Oxidative Stress during Autophagy with a Ratiometric Probe Featuring a Large Probe-Product Spectral Separation.” Sens. Actuators B Chem., 2021, Accepted.

36. Yansheng Xiao, Yunxia Huang, Zhenhua Zeng, Xiao Luo*, Xuhong Qian, Youjun Yang.* “Harnessing Thorpe-Ingold Dialkylation to Access High Hill-percentage pH Probes." Sens. Actuators B Chem., 2021, Accepted.

35. Yansheng Xiao, Fang Hu, Xiao Luo*, Mingming Zhao, Zhenglong Sun*, Xuhong Qian*, Youjun Yang.* “Modulating the pKa Values of Hill-Type pH Probes for Biorelevant Acidic pH Range.” ACS Appl. Bio. Mater., 2021, DOI: 10.1021/acsabm.0c01262.

34. Xiu Xuǂ, Meiling Sunǂ, Xiao Luoǂ, Ziqian Zhang, Lin Su, Lingfei Cui, Zhihui Zhu, Xicun Lu, Rui Wang, Feng Han*, Xuhong Qian, Youjun Yang.* “One-Electron Reduction Triggered Nitric Oxide Release for Ischemia-Reperfusion Protection.” Free Radic. Biol. Med., 2021, 164, 13-19.

33. Kai Xin^‡, Xinxing Li^‡, Yinghua Guo^‡, Youhuan Zhong^‡, Jungang Wang, Haotian Yang, Jie Zhao, Chunlei Guo, Yunxia Huang, Zuhai Lei, Yi-Lun Ying, Xiao Luo*, Haolu Wang, Xuhong Qian, Wen Yang*, Xiaowen Liang*, Youjun Yang*. “A Mono-Chromophoric Approach to Succinct Ratiometric Fluorescent Probes without Probe-Product Crosstalk.” CCS Chemistry, 2020, 2, 2307–2315.

32. Xiao Luo, Yan Chen, Yanchun Li, Zhenglong Sun*, Weihong Zhu*, Xuhong Qian*, Youjun Yang*, “Structurally-thrifty and visible-absorbing fluorophores.” Spectrochimica Acta Part A, 2021, 245, 118907.

31. Luyan Gu^†, Lujia Zhang^†, Xiao Luo*, Ying Zheng, Zhiwei Ye, Meng Lv, Jinquan Chen, Chunlai Chen*, Yi Xiao, Weihong Zhu, Xuhong Qian, Youjun Yang*. “The Mechano Donor-Acceptor Coupling (MDAC) Approach for Uni-directional Multi-State Fluorochromism.” Sci China: Chem., 2020, DOI: 10.1007/s11426-020-9874-6.

30. Meng Lv^†, Yang Yu^†, María E. Sandoval-Salinas^†, Jianhua Xu, Zuhai Lei*, David Casanova*, Youjun Yang*, Jinquan Chen*. “Engineering the Charge-Transfer State to Facilitate Spin-Orbit Charge Transfer Intersystem Crossing in Spirobis[anthracene]diones.” Angew. Chem. Int. Ed., 2020, doi.org/10.1002/anie.202009439.

29. Dawei Jiang,‡ Lei Cheng,‡ Yudong Xue, Chao Chen, Chaochao Wang, Guoliang Yang, An Xu,* Youjun Yang,* Yun Gao, Weian Zhang*. “Modulation of the lifespan of C. elegans by the controlled release of nitric oxide.” Chem. Sci., 2020, 11, 8785-8792.

28. Xiao Luo, Youjun Yang*, Xuhong Qian*. “Recent progresses on the development of thioxo-naphthalimides.” Chin. Chem. Lett., 2020, DOI: 10.1016/j.cclet.2020.07.009.

27. Xiao Luo, Luyan Gu, Xuhong Qian, Youjun Yang*. “Molecular probe design via the ‘covalent-assembly’” principle. Chem. Commun., 2020, 56, 9067-9078.

26. P. Rogelio Escamilla^#, Yanming Shen^#, Quanjuan Zhang, Derek S. Hernandez, Cecil J. Howard, Xuhong Qian, Daria Y. Filonov, Alexander V. Kinev, Jason B. Shear*, Eric V. Anslyn*, Youjun Yang*. “2-Amino-3’-dialkylaminobiphenyl-based Fluorescent Intracellular Probes for Nitric Oxide Surrogate N₂O₃.” Chem. Sci., 2020,11, 1394-1403

25. Xiao Luo, Jin Li, Jie Zhao, Luyan Gu, Xuhong Qian*, Youjun Yang*. “A General Approach to the Design of High-Performance Near-Infrared (NIR) D-p-A Type Fluorescent Dyes.” Chin. Chem. Lett., 2019, 30, 839-846. 

24. Zuhai Lei, Kai Xin, Shaobing Qiu, Liling Hou, Xiangming Meng*, Youjun Yang*. “A Threshold-Limited Fluorescence Probes for Viscosity.” Front. Chem., 2019, 7, 342. 

23. Xiao Luo, Liujia Qian, Yansheng Xiao, Yao Tang, Yang Zhao, Xia Wang, Luyan Gu, Zuhai Lei, Jianming Bao, Jiahui Wu, Tingting He, Fupin Hu, Jing Zheng, Honglin Li, Weiping Zhu, Lei Shao, Xiaojing Dong, Daijie Chen*, Xuhong Qian*, Youjun Yang*. “A Diversity-Oriented Rhodamine Library for Wide-Spectrum Bactericidal Agents with Low Inducible Resistance against Resistant Pathogens.” Nat. Commun., 2019, 10, 258. 

22. Shaobing Qiu, Dongdong Dai, Chunlei Guo, Zhenglong Sun, Hui Li, Xuhong Qian*, Youjun Yang*. “Amino-substituted C-coumarins: Synthesis, Spectral Characterizations and Their Applications in Cell Imaging” Dyes Pigments, 2019, 163, 55-61.

21. Shaobing Qiu, Chunlei Guo, Mingkang Wang, Zhenglong Sun, Hui Li, Xuhong Qian* and Youjun Yang*. “Mild Dealkylative N-Nitrosation of N,N-dialkylaniline Derivatives for Convenient Preparation of Photo-Triggered And Photo-Calibrated NO Donors.” Org. Chem. Front., 2018, 5, 3206-3209. 

20. Haihong He, Tingting He, Ziqian Zhang, Xiu Xu, Huibin Yang, Xuhong Qian, YoujunYang*. “Ring-restricted N-nitrosated Rhodamine as a Green-ight Triggered, Orange-Emission Calibrated and Fast-Releasing Nitric Oxide Donor.” Chin. Chem. Lett., 2018, 10, 1497-1499. 

18. Haihong He, Yuxin Liu, Zhongneng Zhou, Chunlei Guo, Hong-Yin Wang, Zhuang Wang, Xueli Wang, Ziqian Zhang, Fu-Gen Wu, Haolu Wang, Daijie Chen, Dahai Yang, Xiaowen Liang,* Jinquan Chen,* Shengmin Zhou,* Xin Liang,* Xuhong Qian, Youjun Yang.* A Photo-Triggered and Photo-Calibrated Nitric Oxide Donor: Rational Design, Spectral Characterizations, and Biological Applications. Free Radical Biol. Med., 2018, DOI://FRB_FRBM-D-18-00121.

17. Xiao Luo, Haotian Yang, Haolu Wang, Zhiwei Ye, Zhongneng Zhou, Luyan Gu, Jinquan Chen , Yi Xiao, Xiaowen Liang*, Xuhong Qian, and Youjun Yang*. Highly Sensitive Hill-Type Small-Molecule pH Probe That Recognizes the Reversed pH Gradient of Cancer Cells. Anal. Chem., 2018, 90, 5803–5809

16. Haihong He, Yuxin Liu, Zhongneng Zhou, Yang Xia, Yingxue Qi, Zhuang Wang, Hong-Yin Wang, Xueli Wang, Jianming Bao, Ziqian Zhang, Fu-Gen Wu, Haolu Wang, Daijie Chen, Dahai Yang, Xiaowen Liang,* Jinquan Chen,* Shengmin Zhou,* Xin Liang,* Xuhong Qian, Youjun Yang.* “Water-soluble, Green-light Triggered and Photo-Calibrated Nitric Oxide Donors for Biological Applications.” Bioconjugate Chem., 2018, 29, 1194-1198.

15. Haihong He, Zhiwei Ye, Ying Zheng, Xiu Xu, Chunlei Guo, Yi Xiao,* Wei Yang,* Xuhong Qian,* and Youjun Yang*. “Super-Resolution Imaging of Lysosomes with a Nitroso-Caged Rhodamine.” Chem. Commum., 2018, 54, 2842-2845.

14. Haihong He, Zhiwei Ye, Yi Xiao,* Wei Yang,* Xuhong Qian,* Youjun Yang*. “Super-Resolution Monitoring of Mitochondrial Dynamics upon Time-Gated Photo-Triggered Release of Nitric Oxide.” Anal. Chem., 2018, 90, 2164-2169. 

13. Zuhai Lei, Zhenhua Zeng, Xuhong Qian, Youjun Yang*. “A novel chromogenic and fluorogenic scaffold for detection of oxidative radicals.” Chin. Chem. Lett., 2017, 28, 2001-2004.

12. Zuhai Lei, Ping Yue, Xueli Wang, Xinran Li, Yi Li, Haihong He, Xiao Luo, Xiangming Meng*, Jinquan Chen*, Xuhong Qian*, Youjun Yang*. “TPZ, a bright centrosymmetric two-photon scaffold for bioimaging.” Chem. Commun., 2017, 53, 10938-10941.

11. Zuhai Lei, Xinran Li, Xiao Luo, Haihong He, Jing Zheng, Xuhong Qian, Youjun Yang*. “Bright, Stable and Biocompatible Organic Fluorophores Absorbing/Emitting in the Deep Near-Infrared Spectral Region.” Angew. Chem. Int. Ed., 2017, 56, 2979-2983. Highlighted by Sci. Transl. Med, DOI: 10.1126/scitranslmed.aam6065.

10. Ziqian Zhang, Yi Li, Haihong He, Xuhong Qian, Youjun Yang*. “Mild Chemo-Triggered Genetration of a Fluorophore-Tethered Diazoalkane Species via Smiles Rearrangement.” Org. Lett., 2016, 18, 4674-4677.

9.  Ziqian Zhang, Jiayao Wu, Zhihao Shang, Chao Wang, Jiagao Cheng, Xuhong Qian, Yi Xiao*, Zhiping Xu*, Youjun Yang.* “Photo-Calibrated NO release from N-Nitrosated Napthalimides upon One-Photon or Two-Photon Irradiation.” Anal. Chem., 2016, 88, 7274-7280.

8.  Quanjuan Zhang, Na Zhang, Yi-Tao Long, Xuhong Qian, Youjun Yang*. “Understanding the Selectivity of a Multi-Channel Fluorescent Probe for Peroxynitrite Over Hypochlorite.” Bioconjugate Chem., 2016, 27, 341-353.

7.  Zuhai, Lei; Xinran Li; Yi Li; Xiao Luo; Miaomiao Zhou; Youjun Yang*. “Synthesis of Sterically Protected Xanthene Dyes with Bulky Groups at C-3’ and C-7’.” J. Org. Chem., 2015, 80, 11538-11543.

6.  Yanming Shen, Zhihao Shang, Yanhong Yang, Shaojia Zhu, Xuhong Qian, Ping Shi*, Jing Zheng*, and Youjun Yang*. “Structurally Rigid 9-Amino-benzo[c]cinnoliniums Make Up a Class of Compact and Large Stokes-Shift Fluorescent Dyes for Cell-Based Imaging Applications.” J. Org. Chem., 2015, 80, 5906−5911.

5.  Yanming Shen, Quanjuan Zhang, Xuhong Qian, and Youjun Yang*. “Practical Assay for Nitrite and Nitrosothiol as an Alternative to the Griess Assay or the 2,3-Diaminonaphthalene Assay.” Anal. Chem., 2015, 87, 1274-1280.

4.  Ziqian Zhang, Baoyan Zhang, Xuhong Qian, Zhong Li, Zhiping Xu*, Youjun Yang*. Simultaneous Quantification of Hg²⁺ and MeHg⁺ in Aqueous Media by a Single Fluorescent Probe via Multiplexing in the Time Domain. Anal. Chem., 2014, 86, 11919-11924.

3.  Linlin Song, Zuhai Lei, Baoyan Zhang, Zhiping Xu*, Zhong Li* and Youjun Yang*. “A Zero-Background Fluorescent Probe for Hg²⁺ Designed via the Covalent-Assembly Principle.” Anal. Methods, 2014, 6, 7597-7600.

2.  Zuhai Lei, Youjun Yang*. A concise colorimetric and fluorimetric probe for Sarin related threats designed via the covalent-assembly approach. J. Am. Chem. Soc., 2014, 136, 6594−6597. Highlight in Advances in Engineering.

1.  Quanjuan Zhang, Zhichuan Zhu, Yongli Zheng, Jiagao Cheng, Na Zhang, Yi-Tao Long, Jing Zheng, Xuhong Qian, and Youjun Yang*. “A Three-Channel Fluorescent Probe That Distinguishes Peroxynitrite from Hypochlorite.” J. Am. Chem. Soc., 2012, 134, 18479-18482.

Below are publications from graduate and Post-doc works.

7.  Youjun Yang, Balazs Szamosfalvi, Jerry Yee, Stanley Frinak, Eric V. Anslyn*. “Development of an online citrate/Ca²⁺ sensing system for dialysis,” Analyst, 2011, 136, 317-320.

6.  Youjun Yang, Stephanie K. Seidlits, Michelle M. Adams, Vincent M. Lynch, Christine E. Schmidt, Eric V. Anslyn*, Jason B. Shear*. “A highly selective low background fluorescent imaging agent for nitric oxide,” J. Am. Chem. Soc., 2010, 132, 13114-13116.

5.  Youjun Yang, Mark Lowry, Xiangyang Xu, Jorge O. Escobedo, Martha Sibrian -Vazquez, Lisa Wong, Corin M. Schowalter, Timothy J. Jensen, Frank R. Fronczek, Isiah M. Warner, Robert M. Strongin*. “Seminaphthofluorones are a family of water-soluble, low molecular weight, NIR-emitting fluorophores,” Proc. Natl. Acad. Sci. USA2008, 105, 8829-8834. Highlights in Chemical and Engineering News, “Near-IR Imaging Goes Further”, September 22, 2008 issue.

4.  Youjun Yang, Mark Lowry, Corin M. Schowalter, Sayo O. Fakayode, Jorge O. Escobedo, Xiangyang Xu, Huating Zhang, Timothy J. Jensen, Frank R. Fronczek, Isiah M. Warner, Robert M. Strongin*. “An organic white light-emitting fluorophore,” J. Am. Chem. Soc., 2006, 128, 14081 -14092.(Addition and Correction) J. Am. Chem. Soc., 2007, 129, 1008-1008. Highlights in Biophotonics International, “Fluorophores Emit White Light”, December 2006 issue and in Photonics Spectra, “White Light Emitting Fluorophore has Solid State Applications”, January 2007 issue.

3.  Youjun Yang, Jorge O. Escobedo, Alexander Wong, Corin M. Schowalter, Michael C. Touchy, Lijuan Jiao, William E. Crowe, Frank R. Fronczek, Robert M. Strongin*. “A convenient preparation of xanthene dyes,” J. Org. Chem., 2005, 70 (17), 6907-6912.

2.  Youjun Yang, Patrick T. Lewis, Jorge. O. Escobedo, Nadia N. St. Luce, Dale W. Treleaven, Robert L. Cook, Robert M. Strongin*. “Mild Colorimetric Detection of Sialic Acid”, Coll. Czech. Chem. Comms., 2004, 69, 1282-1291.

1.  Guan-Wu Wang*, Li-Juan Jiao, Er-Hong Hao, Yu-Ming Lu, You-Jun Yang. “Aggregation properties of an amphiphilic methanofullerene derivative in THF-H₂O solvent mixtures”, Chin. Chem. Letts., 2004, 15, 579-582.

团队成员：

博士后：罗潇

毕业博士：沈龑鸣、张泉娟、张子谦、雷祖海、何海红、罗潇、肖彦胜

毕业硕士：李欣然、宋琳琳、尚志浩、李义、辛凯、曾振华、顾露燕、徐秀、赵杰

在读博士：郁杨、郭颖华、李紧、邢林峰、汪明康、董严、鲁锡存、尹蕾

在读硕士：李艳春、黄云霞、陈伟超、胡心茹、庄晓莉、李红菊、刘彬、姚成、朱玉峰