Research

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 quite large systems with reasonable accuracy. In the Cluster Approach, the parts of the enzyme that are not modeled explicitly are approximated by a homogenenous polarizable medium. Using this 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:

185.
Mario Prejanò, Jana Škerlová, Pål Stenmark, Fahmi Himo,
Reaction Mechanism of Human PAICS Elucidated by Quantum Chemical Calculations,
J. Am. Chem. Soc. 2022, 14258–14268.
[[link]]
178.
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]]
171.
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]]
158.
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.
[link]

For recent reviews, see:

187.
Xiang Sheng, Fahmi Himo,
The Quantum Chemical Cluster Approach in Biocatalysis,
Acc. Chem. Res. 2023, 56, 938–947
[[link]]
174.
Xiang Sheng, Fahmi Himo,
Mechanisms of Metal-Dependent Non-Redox Decarboxylases from Quantum Chemical Calculations,
Comput. Struct. Biotech. J. 2021, 19, 3176–3186.
[[link]]
162.
Xiang Sheng, Masoud Kazemi, Ferran Planas, Fahmi Himo,
Modeling Enzymatic Enantioselectivity using Quantum Chemical Methodology,
ACS Catal. 2020, 10, 6430−6449.
[[link]]

 

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. The accuracy of modern quantum chemical methods, in particular DFT, has proven to be sufficiently high to achieve this.

For some recent applications, see:

191.
Maria Biosca, Kálmán J. Szabó, Fahmi Himo,
Mechanism of Asymmetric Homologation of Alkenylboronic Acids with CF3-diazomethane via Borotropic Rearrangement,
J. Org. Chem. 2024, 89, 4538–4548.
[[link]]
188.
Srimantra Manna, Joannes Peters, Aitor Bermejo-López, Fahmi Himo, Jan-E. Bäckvall,
Mechanistic Studies on Iron-Catalyzed Dehydrogenation of Amines Involving Cyclopentadienone Iron Complexes – Evidence for Stepwise Hydride and Proton Transfer,
ACS Catal. 2023, 13, 8477–8484.
[[link]]

179.
Qiang Wang, Maria Biosca, Fahmi Himo, Kálmán J. Szabó,
Electrophilic Fluorination of Alkenes via Bora-Wagner-Meerwein Rearrangement. Access to β-Difluoroalkyl Boronates,
Angew. Chem. Int. Ed. 2021, 60, 26327-26331.
[[link]]
177.
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]]
175.
Stefano Santoro, Fahmi Himo,
Mechanism of the Kinugasa Reaction Revisited,
J. Org. Chem. 2021, 86, 10665–10671.
[[link]]

For recent reviews, see:

180.
Akinobu Matsuzawa, Jeremy N. Harvey, Fahmi Himo,
On the Importance of Considering Multinuclear Metal Sites in Homogeneous Catalysis Modeling,
Topics Catal. 2022, 65, 96–104.
[[link]]
166.
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.
[link]
157.
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.
[link]

 

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:

189.
Gantulga Norjmaa, Julius Rebek Jr.,Fahmi Himo,
Modeling Amine Methylation in Methyl Ester Cavitand,
Chem. Eur. J. 2024, 30, e202303911.
[[link]]
164.
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]]
156.
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.
[link]
147.
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]]
138.
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]]