Our research activities are concerned with the application of quantum chemical methods to investigate both enzymatic and homogeneous catalysis.

Quantum chemical modeling of enzymatic reactions

We use quantum chemical methods, predominantely density functional theory (DFT), to model enzyme active sites and reactions. Using DFT, it is today possible to treat systems consisting of more than 300 atoms quite accurately and routinely. This has allowed for more realistic models of enzyme active site. In the adopted Cluster Approach methodology, the parts of the enzyme that are not included in the model are approximated by a homogenenous polarizable medium.

Using the cluster methodology, we have studied a large number of enzymatic reactions belonging to different enzyme families. In recent years, we have become interested in enzymes used in biocatalytic iapplications.

For reviews/perspectives on the cluster approach, see:

Fahmi Himo,
Recent Trends in Quantum Chemical Modeling of Enzymatic Reactions,
J. Am. Chem. Soc. 2017, 139, 6780–6786.
[[link]] Open Access
Margareta R.A. Blomberg, Tomasz Borowski, Fahmi Himo, Rong-Zhen Liao, Per E.M. Siegbahn,
Quantum Chemical Studies of Mechanisms for Metalloenzymes,
Chem. Rev. 2014, 114, 3601-3658.
[[link]] Open Access
Per E.M. Siegbahn, Fahmi Himo,
The Quantum Chemical Cluster Approach for Modeling Enzyme Reactions,
Wiley Interdisciplinary Reviews, Comput. Mol. Sci. 2011, 1, 323-336.


Quantum chemical modeling of homogeneous catalysis

In this field, we are interested in elucidating reaction mechanisms and origins of various selectivities of both organocatalytic and organometallic reactions. To investigate and explain sources of selectivities, one has typically to reproduce relative transition state energies of 1-2 kcal/mol. The accuracy of modern quantum chemical methods, in particular DFT, has proven to be sufficiently high to achieve this.

For a recent account and some recent applications, see:

Binh Khanh Mai, Kálmán J. Szabó, Fahmi Himo,
Mechanisms of Rh-Catalyzed Oxyfluorination and Oxytrifluoromethylation of Diazocarbonyl Compounds with Hypervalent Fluoroiodine,
ACS Catal. 2018, 8, 4483–4492.
Marcin Kalek, Fahmi Himo,
Mechanism and Selectivity of Cooperatively-Catalyzed Meyer-Schuster Rearrangement/Tsuji-Trost Allylic Substitution. Evaluation of Synergistic Catalysis by Means of Combined DFT and Kinetics Simulations,
J. Am. Chem. Soc. 2017, 139, 10250–10266.
[[link]] Open Access
Stefano Santoro, Marcin Kalek, Genping Huang, Fahmi Himo,
Elucidation of Mechanisms and Selectivities of Metal-Catalyzed Reactions using Quantum Chemical Methodology,
Acc. Chem. Res. 2016, 49, 1006–1018.
[[link]] Open Access
Stefano Santoro, Rong-Zhen Liao, Tommaso Marcelli, Peter Hammar, Fahmi Himo,
Theoretical Study of Mechanism and Stereoselectivity of Catalytic Kinugasa Reaction,
J. Org. Chem. 2015, 80, 2649–2660.
[[link]] Open Access