博士（东京大学）

硕士（京都大学）

学士（京都大学）

Hajime Hirao教授分别于1998年和2000年在京都大学获得学士和硕士学位，并于2004年在东京大学获得博士学位。他在耶路撒冷希伯来大学、埃默里大学和京都大学进行了博士后研究。从学生时代开始，他就在诺华公司、南洋理工大学和香港城市大学等多家机构从事计算化学研究。他的研究小组感兴趣的是，通过计算得出化学反应和自然界和实验室中发生的分子相互作用的一般原理，以及与实验家一起合理设计治疗性分子和其他类型的功能分子。

该小组的具体研究主题包括：
1. 开发用于分析化学反应性和分子相互作用的直观吸引人的方法：反应性混合轨道（RHO）；反应性键轨道（RBO）；能量分解分析；用于化学目的的分子波功能的重建。
2. 开发独特的分子力学（MM）力场参数化方案：局部Hessian近似（PHF）；完全Hessian近似（FHF）;内部Hessian近似（IHF）；几何修正（Katachi）；遗传和其他优化算法；机器学习Python等
3. 酶催化：金属酶，蛋白酶等；密度泛函理论（DFT）;从头算量子化学；量子力学和分子力学（QM / MM）； ONIOM；分子动力学（MD）；催化循环； QM / MM能量分解；自由能计算。
4. 计算药物设计：发现有效和选择性的酶抑制剂；对接模拟分析蛋白质-配体相互作用；药物代谢基于机制的灭活（MBI）；中枢神经系统（CNS）；β-内酰胺类抗生素；靶向DNA的抗癌药物。
5. 生物无机化学：血红素酶（细胞色素P450等）；非血红素酶（肌醇加氧酶（MIOX），羟乙基膦酸酯双加氧酶（HEPD）等；铁（IV）氧代中间体的高自旋反应性；带有合成配体的金属-氧配合物；C-H键激活。
6. 均相和非均相催化：过渡金属催化；光催化反应；主族化学有机催化由异质系统（例如纳米颗粒和金属有机框架（MOF））催化的反应；机器学习QM / QM杂交。
7. 多孔材料：MOF；柱芳烃;沸石分子有机笼多孔有机框架（POF）；客体分子的吸附、分离、纯化、催化活化和感测；多孔系统的QM / MM，MM和平面波密度泛函理论（DFT）处理。

1. Liu, C.-Y.; Chen, X.-R.; Chen, H.-X.; Niu, Z.; Hirao, H.; Braunstein, P.; Lang, J.-P. "Ultrafast Luminescent Light-Up Guest Detection Based on the Lock of the Host Molecular Vibration", J. Am. Chem. Soc. 2020, 142, 6690-6697.
2. Ogoshi, T. Sueto, R.; Yagyu, M.; Kojima, R.; Kakuta, T.; Yamagishi, T.; Doitomi, K.; Tummanapelli, A.; Hirao, H.; Sakata, Y.; Akine, S.; Mizuno, M. "Molecular Weight Fractionation by Confinement of Polymer in One-dimensional Pillar[5]arene Channels", Nat. Commun. 2019, 10, 479.
3. Xu, K.; Hirao, H. "Revisiting the Catalytic Mechanism of Mo-Cu Carbon Monoxide Dehydrogenase Using QM/MM and DFT Calculations", Phys. Chem. Chem. Phys. 2018, 20, 18938-18948 (Outside Back Cover).
4. Wang, R.; Ozhgibesov, M.; Hirao, H. "Analytical Hessian Fitting Schemes for Efficient Determination of Force-Constant Parameters in Molecular Mechanics", J. Comput. Chem. 2018, 39, 307-318 (Front Cover).
5. Ghalei, B.; Sakurai, K.; Kinoshita, Y.; Isfahani, A. P.; Song, Q.; Doitomi, K.; Furukawa, S.; Hirao, H.; Kusuda, H.; Kitagawa, S.; Sivaniah, E. "Enhanced Selectivity in Mixed Matrix Membranes for CO2 Capture through Efficient Dispersion of Amine-Functionalized MOF Nanoparticles", Nat. Energy 2017, 2, 17086.
6. Wang, R.; Ozhgibesov, M.; Hirao, H. "Partial Hessian Fitting for Determining Force Constant Parameters in Molecular Mechanics", J. Comput. Chem. 2016, 37, 2349-2359 (Inside Cover).
7.  Wu, C.; Yue, G.; Nielsen, C. D.-T.; Xu, K.; Hirao, H.; Zhou, J. S. "Asymmetric Conjugate Addition of Organoboron Reagents to Common Enones Using Copper Catalysts", J. Am. Chem. Soc. 2016, 138, 742-745
8. Cho, K.-B.; Hirao, H.; Shaik, S.; Nam, W. "To Rebound or Dissociate? This is the Mechanistic Question in C–H Hydroxylation by Heme and Nonheme Metal-oxo Complexes", Chem. Soc. Rev. 2016, 45, 1197-1210.
9. Gazi, S.; Ng, W. K. H.; Ganguly, R.; Moeljadi, A. M. P.; Hirao, H.; Soo, H. S. "Selective Photocatalytic C–C bond Cleavage under Ambient Conditions with Earth Abundant Vanadium Complexes", Chem. Sci. 2015, 6, 7130-7142.
10. Xu, K.; Wang, Y.; Hirao, H. "Estrogen Formation via H-Abstraction from the O–H Bond of gem-Diol by Compound I in the Reaction of CYP19A1: Mechanistic Scenario Derived from Multiscale QM/MM Calculations", ACS Catal. 2015, 5, 4175-4179 (included in “Catalysis in Singapore”).
11. Ribeiro, A. J. M.; Yang, L.; Ramos, M. J; Fernandes, P. A.; Liang, Z.-X.; Hirao, H. "Insight into Biological Nitrile Reduction: A QM/MM Study of the Catalytic Mechanism of Nitrile Reductase", ACS Catal. 2015, 5, 3740-3751 (included in “Catalysis in Singapore”).
12. Chuanprasit, P.; Goh, S. H.; Hirao, H. "Benzyne Formation in the Mechanism-Based Inactivation of Cytochrome P450 by 1-Aminobenzotriazole and N-Benzyl-1-Aminobenzotriazole: Computational Insights", ACS Catal. 2015, 5, 2952-2960 (included in “Catalysis in Singapore”).
13. Cui, J.; Li, Y.; Ganguly, R.; Inthirarajah, A.; Hirao, H.; Kinjo, R. "Metal-Free 𝜎-Bond Metathesis in Ammonia Activation by a Diazadiphosphapentalene", J. Am. Chem. Soc. 2014, 136, 16764-16767.
14.  Thellamurege, N. M.; Hirao, H. "Effect of Protein Environment within Cytochrome P450cam Evaluated Using a Polarizable-Embedding QM/MM Method", J. Phys. Chem. B 2014, 118, 2084-2092.
15.  Wang, X.; Hirao, H. "ONIOM(DFT:MM) Study of the Catalytic Mechanism of myo-Inositol Monophosphatase: Essential Role of Water in Enzyme Catalysis in the Two-Metal Mechanism", J. Phys. Chem. B 2013, 117, 833-842.
16. Hirao, H.; Morokuma, K. "ONIOM(DFT:MM) Study of 2-Hydroxyethylphosphonate Dioxygenase: What Determines the Destinies of Different Substrates?", J. Am. Chem. Soc. 2011, 133, 14550-14553.
17. Hirao, H.; Morokuma, K. "Insights into the (Superoxo)Fe(III)Fe(III) Intermediate and Reaction Mechanism of myo-Inositol Oxygenase: DFT and ONIOM(DFT:MM) Study", J. Am. Chem. Soc. 2009, 131, 17206-17214.
18.  Irie, O.; Kosaka, T.; Ehara, T.; Yokokawa, F.; Kanazawa, T.; Hirao, H.; Iwasaki, A.; Sakaki, J.; Teno, N.; Hitomi, Y.; Iwasaki, G.; Fukaya, H.; Nonomura, K.; Tanabe, K.; Koizumi, S.; Uchiyama, N.; Bevan, S. J.; Malcangio, M.; Gentry, C.; Fox, A. J.; Yaqoob, M.; Culshaw, A. J.; Hallett, A. "Discovery of Orally Bioavailable Cathepsin S Inhibitors for the Reversal of Neuropathic Pain", J. Med. Chem. 2008, 51, 5502-5505.
19. Shaik, S.; Hirao, H.; Kumar, D. "Reactivity Patterns of High-Valent Iron Oxo Species in Enzymes and Synthetic Reagents: A Tale of Many States", Acc. Chem. Res. 2007, 40, 532-542
20. Hirao, H.; Kumar, D.; Thiel, W.; Shaik, S. "Two States and Two More in the Mechanisms of Hydroxylation and Epoxidation by Cytochrome P450", J. Am. Chem. Soc. 2005, 127, 13007-13018.