PhD (The University of Tokyo)
MEng (Kyoto University)
BEng (Kyoto University)）

Hajime Hirao obtained his BEng and MEng degrees from Kyoto University in 1998 and 2000, respectively, and his PhD from The University of Tokyo in 2004. He did his postdoctoral studies at The Hebrew University of Jerusalem, Emory University, and Kyoto University. Since his student days, he has been engaged in computational chemistry research at various institutions such as Novartis, Nanyang Technological University, and City University of Hong Kong. His research group is interested in computationally deriving general principles of chemical reactions and molecular interactions occurring in nature and labs, and also in rationally designing therapeutic and other types of functional molecules with experimentalists.

Specific research themes of the group include the following:
1. Development of intuitively appealing methods for analyzing chemical reactivities and molecular interactions: reactive hybrid orbital (RHO); reactive bond orbital (RBO); energy decomposition analysis; reconstruction of molecular wave functions for chemistry purposes.
2. Development of unique molecular mechanics (MM) force-field parametrization schemes: partial hessian fitting (PHF); full hessian fitting (FHF); internal hessian fitting (IHF); geometry amendment (Katachi); genetic and other optimization algorithms; machine learning; Python, etc.
3. Enzyme catalysis: metalloenzymes, proteases, etc.; density functional theory (DFT); ab initio quantum chemistry; quantum mechanics and molecular mechanics (QM/MM); ONIOM; molecular dynamics (MD); catalytic cycles; QM/MM energy decomposition; free energy calculations.
4. Computational drug design: discovery of potent and selective enzyme inhibitors; docking simulation; analysis of protein-ligand interactions; drug metabolism; mechanism-based inactivation (MBI); central nervous system (CNS); β-lactam antibiotics; DNA-targeting anti-cancer drugs.
5. Bioinorganic chemistry: heme enzymes (cytochrome P450, etc.); nonheme enzymes (myo-inositol oxygenase (MIOX), hydroxyethylphosphonate dioxygenase (HEPD), etc.); high-spin reactivity of iron(IV)-oxo intermediates; metal-oxo complexes bearing synthetic ligands; C–H bond activation.
6. Homogeneous and heterogeneous catalysis: transition-metal catalysis; photocatalytic reactions; main group chemistry; organocatalysis; reactions catalyzed by heterogeneous systems such as nanoparticles and metal–organic frameworks (MOFs); machine learning; QM/QM hybridization.
7. Porous materials: MOFs; pillararenes; zeolites; molecular organic cages; porous organic frameworks (POFs); adsorption, separation, purification, catalytic activation, and sensing of guest molecules; QM/MM, MM, and plane-wave density functional theory (DFT) treatments of porous systems.

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.