Our research activities are concerned with the application of quantum chemical methods to the study of catalytic processes.

Three main areas are pursued:

I. 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 study 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 applications, in particular enzymes exhibiting enantioselectivity.

For some recent applications, see:

Ferran Planas, Michael J. McLeish, Fahmi Himo,
Enzymatic Stetter Reaction: Computational Study of the Reaction Mechanism of MenD,
ACS Catal. 2021, 11, 12355–12366.
[[link]] Open Access
Xiang Sheng, Fahmi Himo,
Mechanism of 3-Methylglutaconyl CoA Decarboxylase AibA/AibB: Pericyclic Reaction versus Direct Decarboxylation,
Angew. Chem. Int. Ed. 2020, 59, 22973-22977.
[[link]] Open Access
Xiang Sheng, Fahmi Himo,
Enzymatic Pictet-Spengler Reaction: Computational Study of the Mechanism and Enantioselectivity of Norcoclaurine Synthase,
J. Am. Chem. Soc. 2019, 141, 11230-11238.
Masoud Kazemi, Xiang Sheng, Wolfgang Kroutil, Fahmi Himo,
Computational Study of Mycobacterium smegmatis Acyl Transferase Reaction Mechanism and Specificity,
ACS Catal. 2018, 8, 10698–10706.
[[link]] Open Access

For recent reviews, see:

Xiang Sheng, Fahmi Himo,
Mechanisms of Metal-Dependent Non-Redox Decarboxylases from Quantum Chemical Calculations,
Comput. Struct. Biotech. J. 2021, 19, 3176–3186.
[[link]] Open Access
Xiang Sheng, Masoud Kazemi, Ferran Planas, Fahmi Himo,
Modeling Enzymatic Enantioselectivity using Quantum Chemical Methodology,
ACS Catal. 2020, 10, 6430−6449.
[[link]] Open Access
Fahmi Himo,
Recent Trends in Quantum Chemical Modeling of Enzymatic Reactions,
J. Am. Chem. Soc. 2017, 139, 6780–6786.
[[link]] Open Access


II. 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 rationalize selectivities, one has typically to reproduce relative barriers 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 some recent applications, see:

Ferran Planas, Matteo Costantini, Marc Montesinos-Magraner, Fahmi Himo, Abraham Mendoza,
Combined Experimental and Computational Study of Ruthenium N-Hydroxyphthalimidoyl Carbenes in Alkene Cyclopropanation Reactions,
ACS Catal. 2021, 11, 10950−10963.
[[link]] Open Access
Stefano Santoro, Fahmi Himo,
Mechanism of the Kinugasa Reaction Revisited,
J. Org. Chem. 2021, 86, 10665–10671.
[[link]] Open Access
Man Li, Amparo Sanz-Marco, Samuel Martinez-Erro, Victor García-Vázquez, Binh Khanh Mai, Jacob Fernández-Gallardo, Fahmi Himo, Belén Martín-Matute,
Unraveling the Mechanism of the IrIII-Catalyzed Regiospecific Synthesis of α-Chlorocarbonyl Compounds from Allylic Alcohols,
Chem. Eur. J. 2020, 65, 14978-14986.
[[link]] Open Access
Qiang Wang, Marvin Lübcke, Maria Biosca, Martin Hedberg, Lars Eriksson, Fahmi Himo, Kálmán J. Szabó,
Enantioselective Construction of C-F Quaternary Stereocenters by Organocatalytic Fluorocyclization,
J. Am. Chem. Soc. 2020, 142, 20048–20057.
[[link]] Open Access
Oriana Brea, Kálmán J. Szabó, Fahmi Himo,
Mechanisms of Formation and Rearrangement of Benziodoxole-Based CF3 and SCF3 Transfer Reagents,
J. Org. Chem. 2020, 85, 15577–15585.
[[link]] Open Access

For recent reviews, see:

Binh Khanh Mai, Fahmi Himo,
Mechanisms of Metal-Catalyzed Electrophilic F/CF3/SCF3 Transfer Reactions from Quantum Chemical Calculations,
In: Lledós A., Ujaque G. (eds) New Directions in the Modeling of Organometallic Reactions.
Topics in Organometallic Chemistry 2020, 67, pp 39-56. Springer, Cham.
Jeremy N. Harvey, Fahmi Himo, Feliu Maseras, Lionel Perrin,
Scope and Challenge of Computational Methods for Studying Mechanism and Reactivity in Homogeneous Catalysis,
ACS Catal. 2019, 9, 6803-6813.
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


III. Modeling of reactions in confined spaces

We have in recent years started to investigate a number of reactions taking place in confined spaces.

Here are some representative publications:

Henrik Daver, Julius Rebek Jr., Fahmi Himo,
Modeling the Reaction of Carboxylic Acids and Isonitriles in a Self-Assembled Capsule,
Chem. Eur. J. 2020, 26, 10861-10870.
[[link]] Open Access
Oriana Brea, Henrik Daver, Julius Rebek Jr., Fahmi Himo,
Modeling Decomposition of N-Nitrosoamides in a Self-Assembled Capsule,
J. Org. Chem. 2019, 84, 7354-7361.
Henrik Daver, Andrés G. Algarra, Jeremy N. Harvey, Julius Rebek Jr., Fahmi Himo,
Mixed Explicit-Implicit Solvation Approach for Modeling of Alkane Complexation in Water-Soluble Self-Assembled Capsules,
J. Am. Chem. Soc. 2018, 140, 12527–12537.
[[link]] Open Access
Henrik Daver, Jeremy N. Harvey, Julius Rebek Jr., Fahmi Himo,
Quantum Chemical Modeling of Cycloaddition Reaction in a Self-Assembled Capsule,
J. Am. Chem. Soc. 2017, 139, 15494–15503.
[[link]] Open Access