面向当前创新药物研究中的挑战，何伟研究组主要在下述两个方向展开研究。（1）金属纳米有机催化。根据精细化学品和药物合成的需求，我们立足于金属纳米材料的可控合成，通过调控催化剂活性来实现高效高选择性的有机反应, 包括含硅化合物的合成化学和化学生物学研究; (2)基于片段的药物发现。我们结合片段筛选和基于结构的药物设计，发现特异性靶向新型、可药性低的蛋白靶点的功能有机小分子(如溴域蛋白、去泛素化酶等)，并展开化学生物学及早期药物发现工作。

用硅来替代药物分子中的碳的策略是药物研发中的一个合理而又诱人的途径。要实现这一策略，必须克服方法，合成和概念上的诸多挑战。我们从发展新化学方法入手，合成了多种新型的硅替代药物单元和药物分子，并在临床前研究中展示了这一策略的诱人前景。我们在研究中，使用多学科交叉手段，包括纳米材料合成，有机化学，药物化学，以及基于片段的药物设计等，促进了这些手段的融合。

奖励

2013年 清华大学“221”基础研究青年人才计划

2011，2015， 2016， Bayer Investigator Award

2012, 2013, Janssen Investigator Award

1.Liu, C.; Zhang, Q.; Li, H.; Guo, S.; Xiao, B.; Deng, W.; Liu, L.; *He, W. Cu/Fe Catalyzed Intermolecular Oxidative Amination of Primary Benzylic C-H Bonds. Chem. Eur. J. 2016, DOI: chem.201600107. (HOT paper)

2.Zhang, Q.-W.; An, K.; Liu, L.-C.; Guo, S.; Jiang, C.; Guo, H.; *He, W. Silacyclobutane: a New C-H Silylation Reagent. Angew. Chem. doi ： 10.1002/anie.201602376

3.Zhao, C.; Liu, L-C.; Wang, J.; Jiang, C.; Zhang, Q.-W.; *He, W. Rh(I)-Catalyzed Insertion of Allenes into C−C Bonds of Benzocyclobutenols. Org. Lett. 2016, 18, 328-331.

4.Guo, H.; Chen, X.; Zhao, C.; *He, W. Suzuki-type Cross Coupling between Aryl Halides and Silylboranes for the Syntheses of Aryl Silanes. Chem. Commun. 2015, 51, 17410 – 17412.

5.Ji, Y.; Wu, Y.; Zhao, G.; Wang, D.; Liu, L.; He, W.; *Li, Yadong. Porous bimetallic Pt-Fe nanocatalysts for highly efficient hydrogenation of acetone. Nano Research 2015. 8, 2706-2713.

6.Zhang, Q.; An, K.; *He, W. Rh Catalyzed Enantioselective Intramolecular C-H Silylation for the Syntheses of Planar Chiral Metallocene Siloles. Angew. Chem. Int. Ed., 2015, 54, 6918-6921.

7.Guo, H.; Xiuling Y;, Zhi, Y.; Li，Z.; Wu, C.; Zhao, C.; Wang, J.; Yu, Z.; *Ding, Y.; *He, W.; Li. Y. Nanostructuring Gold Wires for Highly Durable Nanocatalysts toward Selective reduction of nitro compounds and azides with organosilanes. Nano Research 2015, 8, 1365-1372 (Cover story)

8.Xiao, B.; Niu, Z.; Wang, Y.; Jia, W.; Shang, J.; Zhang, L.; Wang, D.; Fu, Y.; Zeng, J.; He, W.; Wu, K.; Li, J.; Yang, J.; *Liu, L.; *Li, Y. Copper Nanocrystal Plane Effect on Stereoselectivity of Catalytic Deoxygenation of Aromatic Epoxides. J. Am. Chem. Soc. 2015, 137, 3791-3794.

9.Zhang, Q.; An, K.; *He, W. Catalytic Synthesis of π-Conjugated Silole through Si-C (sp3) Bond Activation. Synlett, 2015, 26, 1145-1152.

10.Dang, S.; Wu, S.; Wang, J.; Li, H.; Huang, M.; He, W.; Li, Y.; Wong, C. C. L.; *Shi, Y. Cleavage of amyloid precursor protein by an archaeal presenilin homologue PSH. PNAS 2015, 112, 3344-3349.

11.Zhao, C.; Jiang, C.; Wang, J.; Wu, C.; Zhang, Q.; *He, W. Enantioselective Syntheses of α-Silyl Amines via a Copper-N-HeterocyclicCarbene Catalyzed Nucleophilic Silicon Transfer to Imines. Asian. J. Org. Chem. 2014, 3, 851-855. (Cover story)

12.Zhang, Z.; Chen, Y.; He, S.; Zhang, J.; Xu, X.; Yang, Y.; Nosheen, F.; Saleem, F.; He, W.;*Wang, X. Hierarchical Zn/Ni-MOF-2 Nanosheet-Assembled Hollow Nanocubes for Multicomponent Catalytic Reactions. Angew. Chem. Int. Ed., 2014, 53, 12517-12521.

13.Zhang, Q.; An, K.; *He, W. Rh Catalyzed Tandem Cyclization/Si-C Activation Reaction for the Synthesis of Siloles. Angew. Chem. Int. Ed. 2014, 53, 5667-5671.

14.Zhang, Z.; Chen, Y.; Xu, X.; Zhang, J.; Xiang, G.; He, W.; *Wang, X. Well-Defined Metal-Organic Framework Hollow Nanocages. Angew. Chem. Int. Ed., 2014, 53, 429-433.

15.Li, L.; Niu, Z.; Cai, S.; Zhi, Y.; Li, H.; Rong, H.; Liu, L.; Liu, L.; *He, W.; *Li, Y. A PdAg Bimetallic Nanocatalyst for Selective Reductive Amination of Nitroarenes. Chem. Comm. 2013, 49, 6843.

16.Zhang, Q.; Cai, S.; Li, L.; Chen, Y.; Rong, H.; Niu, Z.; Liu, J.; *He, W.; *Li, Y. Direct Syntheses of Vinyl Ethers from Benzyl Alcohols via Ag Nanoparticles Catalyzed Tandem Aerobic Oxidation. ACS Catalysis, 2013, 3, 1681-1684.

17.Liu, J.; *Liu, C.; *He, W. Fluorophores and Their Applications as Molecular Probes in Living Cells. Current Organic Chemistry 2013, 17, 564-579.

18.Huang, W.; Choi, W.; Chen, Y.; Zhang, Q.; Deng, H.; He, W.; *Shi, Y. A Proposed Role for Glutamine in Cancer Cell Growth through Acid Resistance. Cell Research 2013, 23, 724-727.

19.Cai, S.; Duan, H.; Rong, H.; Wang, D.; Li, L.; *He, W.; *Li, Y. Highly Active and Selective Catalysis of Bimetallic Rh₃Ni₁ Nanoparticles in the Hydrogenation of Nitroarenes ACS Catalysis, 2013, 3, 608-612.

20.Cai, S.; Rong, H.; Yu, X.; Liu, X.; Wang, D.; *He, W.; *Li, Y. Room Temperature Activation of Oxygen by Monodispersed Metal Nanoparticles: Oxidative Dehydrogenative Coupling of Anilines for Azobenzene Syntheses. ACS Catalysis, 2013, 3, 478-486.

21.Wu, Y.; Cai, S.; Wang, D.; * He, W.; *Li, Y. Syntheses of Water-Soluble Octahedral, Truncated Octahedral and Cubic Pt−Ni Nanocrystals and Their Structure−Activity Study in Model Hydrogenation Reactions. J. Am. Chem. Soc. 2012. 134, 8975-8981.

22. Niu, Z.; Peng, Q.; Zhuang, Z.; *He, W.; *Li, Y. Evidence of an Oxidative-Addition-Promoted Pd-Leaching Mechanism in the Suzuki Reaction by Using a Pd-Nanostru

cture Design. Chem. Eur. J. 2012, 18, 9813-9817.