Theoretical Studies on Organometallic Catalysis

Due to applications in industrial and synthetic processes of catalytic transition-metal reactions, ab initio molecular orbital (MO) and density functional theory (DFT) methods are used to study a series of transition-metal-catalyzed chemical reactions. Here, we focus on reaction mechanisms of transition-metal chiral catalysis involving various classes of elementary reactions such as substitution, migratory insertion, hydrogen transfer, oxidative addition/reductive elimination, metathesis, and nucleophilic addition.

Asymmetric hydrogenation

Chiral alcohols and amines are of importance in pharmaceutical, perfume and agrochemical industries. Asymmetric hydrogenation of ketone/imine is one of major ways to produce chiral alcohol/amine catalyzed by transition metal complexes. A series of theoretical studies have been performed in our group to study the catalytic activity and enantioselectivity which could be affected by the transition metal centers and the coordinated ligands. The calculated results also unveil the intrinsic nature of alcohol and acid assistance in transfer hydrogenation and H2 hydrogenation of ketones. Meanwhile, chemical information of chiral phosphine ligands is used in order to establish a reliable quantitative structure-property relationship (QSPR) model. In general, new framework transition metal catalyst with a high activity and enantioselectivity are hoped to be designed considering factors above, which could be used in industry of ketone/imine hydrogenation in the future.  [This project is supported by NSFC (Grant No. 21072018, 01/01/2011-12/31/2013)]


Theoretical Studies on Catalysis on Surfaces

The first-principles theory and DFT method are used to study the heterogeneous catalysis on surfaces. Here we focus on reaction mechanisms of catalysis on surfaces involving metal oxides related to small molecules activation in sustainable energy field, to unveil the nature of heterogeneous catalysis and build relationship between structures of surfaces and their catalytic activities. 

Computational Biophysical Chemistry

The three-dimensional structure and dynamics are closely related with the function of biomolecules. Biomolecular modelling provides a praticising way to investigate the relationship between the dynamics and the function of the molecule at atom level, the effects of mutations or PH. The computation of thermodynamic and kinetic properties of macromolecules are feasible using simulation methods and powerful supercomputer facilities. They are very useful to design new drugs on biomolecular targets.

Molecular dynamic simulation

Molecular modelling including molecular dynamics or Monte Carlo simulations to simulate dynamic features and compute thermodynamic and kinetic properties. Predicting three-dimensional structure of a protein from its amino acid sequence is a hot field in current structural biology. A lot of amyloid-related diseases are proposed to be related with protein folding and misfolding, such as Alzheimer’s disease (AD), Huntington’s disease (HD) and Parkinson’s disease (PD). In the past 15 years, tremendous advances have been made with the development in experimental and theoretical technologies. Molecular dynamic (MD) simulation is one of the most realistic theoretical methods to predict native-like structures of peptides correctly. It could elucidate the folding features of small proteins at atom level. These dynamic features, which cannot be revealed by the X-ray crystallography, will provide significant insights into the origins of the qualitative differences in behavior and may also gain insight into what is likely to be the first step in the amyloid pathway. 

Drug design 

Besides crystallography, molecular modeling is of importance in structural biology and drug discovery. Using bioinformatic, docking and QSAR tools, we could make it clear on the binding modes of “keys” with the “lock”. The three-dimensional shape of the lock based on experimental (X-ray or NMR structures) or theoretical methods (Homology models), it provides us a chance to design a lead compound to fit the lock precisely.

QM/MM study on transition metal biomolecular systems

Quantum mechanics with molecular mechanics (QM/MM) method is used to investigate biomolecular catalytic mechanisms.

J Software Development

J project aims on the development of a GUI software to construct molecules, display the model, investigate reaction mechanism, perform data mining, build QSAR relationship. This will be used to develop new catalysts based on reaction mechanisms. In addition, some education functions will also be developed such as point group conception.


Research support

The researches in our group are supported in part by grants from the following agencies:

National Natural Science Foundation of China (NSFC Grant No. 22073005 (2021-2024, PI M Lei), 21672018 (2017-2020, PI M Lei), 21373023 (2014-2017, PI: M Lei), 21203006 (2013-2015, PI: X Zhang), 21072018 (2011-2013, PI: M Lei), and 20703003 (2008-2010, PI: M Lei))

The Joint Research Fund of National Natural Science Foundation of China (NSFC) and Royal Society of UK (RS) (NSFC-RS Grant No. 2161101308 (2017-2019, PI: M Lei))

The Special Program for Applied Research on Super Computation of the NSFC-Guangdong Joint Fund (the second phase) (2015-2017, PI M Lei)

Beijing Municipal Natural Science Foundation (BJNSF Grant No. 2162029 (2016-2018, PI M Lei))

Beijing Nova Fund (2005B17, 2005-2008, PI: M Lei)

Scientific Research Foundation for the Returned Overseas Chinese Scholars, MOE (SRF for ROCS, 2006-2008, PI: M Lei)

Open Research Fund of State Key Laboratory of Physical Chemistry of Solid Surfaces, Xiamen Univ. (Grant No. 201811, 2019-2020, PI: M Lei)

Fundamental Research Funds for the Central Universities, MOE (FRFCU Grant No. PYCC1708 (2017, PI: M Lei), XK1527 (2015-2016, PI: M Lei), ZZ1020 (2008-2010, PI: M Lei))

NHwa Pharmaceutical Corp. Foundation (NHwa, 2006-2008, PI: M Lei)

Open Research Fund of State Key Laboratory of Natural and Biomimetic Drugs in Peking Univ. (ORF of SKLNBD Grant No. K20100103, 2009-2011, PI: M Lei)