Theoretical Chemistry Research Group

Research interest

The main goal of the studies carried out at the Theoretical Chemistry Research Group is to provide a theoretical background for ongoing synthetic, material science and structural research at RCNS and also in various Hungarian universities. The theoretical investigations are aimed at revealing the mechanism of chemical reactions and characterizing the structure and reactivity of newly prepared compounds. In these studies, quantum chemical and molecular dynamic simulation methods are applied, but methodological developments are carried out as well.

Current research projects

1) Organocatalytic transformations

Organocatalysis belongs to the most dynamically developing fields of synthetic chemistry. In the past ten years or so, a large number of new synthetic methods have been reported, werein relatively simple chiral organic molecules were used to promote asymmetric transformations. Despite these developments, the information regarding the reaction mechanism is far from complete, the observed stereoselectivity cannot always be easily understood. The working hypothesis of the present proposal is that the most relevant states of the catalytic cycle (i.e. intermediates and transition states that determine the reactivity and the stereochemical outcome of the reactions), can be revealed and characterized in joint theoretical-experimental studies. These states, as well as the effect of catalyst modification, can be identified computationally by using accurate quantum chemical methods. The theoretical predictions can be tested experimentally as well. But how to find an optimal catalyst for a given process? We seek an answer to this question in our research in collaboration with synthetic chemists, Dr. Tibor Soós (RCNS HAS) and Prof. Petri Pihko (University of Jyväskylä).

New stereoselectivity model for diphenylprolinol silyl ether catalyzed Michael additions Foldamer catalysts as new generation of bifunctional thiourea-amine catalysts

Related papers:

  • T. Földes, Á. Madarász, Á. Révész, Z. Dobi, Sz. Varga, A. Hamza, P. R. Nagy, P. M. Pihko, I. Pápai, Stereocontrol in Diphenylprolinol Silyl Ether Catalyzed Michael Additions: Steric Shielding or Curtin-Hammett Scenario?, J. Am. Chem. Soc. 139, 17052 (2017)
  • A. J. Neuvonen, T. Földes, Á. Madarász, I. Pápai, P. M. Pihko, Organocatalysts Fold To Generate an Active Site Pocket for the Mannich Reaction, ACS Catal. 7, 3284 (2017)
  • Á. Madarász, Z. Dósa, S. Varga, T. Soós, I. Pápai, Thiourea Derivatives as Bronsted Acid Organocatalysts, ACS Catal. 6, 4379 (2016)
  • A. Claraz, G. Sahoo, D. Berta, Á. Madarász, I. Pápai, P. M. Pihko, A Catalyst Designed for the Enantioselective Construction of Methyl- and Alkyl-Substituted Tertiary Stereocenters, Angew. Chem. Int. Ed. 55, 669 (2016)
  • M. Kortelainen, A. Suhonen, A. Hamza, I. Pápai, E. Nauha, S. Yliniemela-Sipari, M. Nissinen, P. M. Pihko, Folding Patterns in a Family of Oligoamide Foldamers, Chem. Eur. J. 21, 9493 (2015)
  • E. K. Kemppainen, G. Sahoo, A. Piisola, A. Hamza, B. Kótai, I. Pápai, P. M. Pihko, Mukaiyama–Michael Reactions with trans-2,5-Diarylpyrrolidine Catalysts: Enantioselectivity Arises from Attractive Noncovalent Interactions, Not from Steric Hindrance, Chem. Eur. J. 20, 5983 (2014)
  • B. Kótai, G. Kardos, A. Hamza, V. Farkas, I. Pápai, T. Soós, On the Mechanism of Bifunctional Squaramide-Catalyzed Organocatalytic Michael Addition: A Protonated Catalyst as an Oxyanion Hole, Chem. Eur. J. 20, 5631 (2014)
  • G. Sahoo, H. Rahaman, Á. Madarász, I. Pápai, M. Melarto, A. Valkonen, P. M. Pihko, Dihydrooxazine Oxides as Key Intermediates in Organocatalytic Michael Additions of Aldehydes to Nitroalkenes, Angew. Chem. Int. Ed. 51, 13144 (2012)

2) Reactivity of frustrated Lewis pairs

Frustrated Lewis pairs (FLPs) are bulky donor-acceptor systems in which formation of the dative bond is hindered, leading to diverse reactions with small molecules. They are capable, for example, of cleaving molecular hydrogen heterolytically under mild conditions and of catalyzing hydrogenation of unsaturated substrates. Our current research is focused on further development of the model of FLP-type reactivity, on the design of new FLP systems, and on the detailed characterization of FLP-catalyzed hydrogenation processes. In this field, we are collaborating with Dr. Tibor Soós (RCNS HAS) and Prof. Timo Repo (University of Helsinki).

Intramolecular FLP containing the smallest possible boryl group (BH2) and capable of hydrogen cleavage Asymmetric reduction of imines and enamines is feasible using a binaphthyl-derived chiral intramolecular FLP

Related papers:

  • É. Dorkó, B. Kótai, T. Földes, Á. Gyömöre, I. Pápai, T. Soós, Correlating electronic and catalytic properties of frustrated Lewis pairs for imine hydrogenation, J. Organomet. Chem. 847, 258 (2017)
  • É. Dorkó, M. Szabó, B. Kótai, I. Pápai, A. Domján, T. Soós, Expanding the Boundary of Water Tolerant Frustrated Lewis Pair Hydrogenation: Enhanced Back Strain in the Lewis Acid Enables the Reductive Amination of Carbonyls, Angew. Chem. Int. Ed. 56, 9512 (2017)
  • K. Chernichenko, B. Kótai, M. Nieger, S. Heikkinen, I. Pápai, T. Repo, Replacing C6F5 groups with Cl and H atoms in frustrated Lewis pairs: H2 additions and catalytic hydrogenations, Dalt. Trans. 46, 2263 (2017)
  • V. Iashin, K. Chernichenko, I. Pápai, T, Repo, Atom-Efficient Synthesis of Alkynylfluoroborates Using BF3-Based Frustrated Lewis Pairs, Angew. Chem. Int. Ed. 55, 14146 (2017)
  • K. Chernichenko, M. Lindqvist, B. Kótai, M. Nieger, K. Sorochkina, I. Pápai, T. Repo, Metal-Free sp2-C–H Borylation as a Common Reactivity Pattern of Frustrated 2-Aminophenylboranes, J. Am. Chem. Soc. 138, 4860 (2016)
  • Á. Gyömöre, M. Bakos, T. Földes, I. Pápai, A. Domján, T. Soós, Moisture-Tolerant Frustrated Lewis Pair Catalyst for Hydrogenation of Aldehydes and Ketones, ACS Catal. 5, 5366 (2015)
  • M. Lindqvist, K. Borre, K. Axenov, B. Kótai, M. Nieger, M. Leskelä, I. Pápai, T. Repo, Chiral Molecular Tweezers: Synthesis and Reactivity in Asymmetric Hydrogenation, J. Am. Chem. Soc. 137, 4038 (2015)
  • K. Chernichenko, B. Kótai, I. Pápai, V. Zhivonitko, M. Nieger, M. Leskelä, T. Repo, Intramolecular Frustrated Lewis Pair with the Smallest Boryl Site: Reversible H2 Addition and Kinetic Analysis, Angew. Chem. Int. Ed. 54, 1749 (2015)
  • É. Dorkó, E. Varga, T. Gáti, T. Holczbauer, I. Pápai, H. Mehdi, T. Soós, Steric Control of Geminal Lewis Pair Behavior: Frustration Induced Dyotropic Rearrangement, Synlett 25, 1525 (2014)
  • K. Chernichenko, Á. Madarász, I. Pápai, M. Nieger, M. Leskelä, T. Repo, A frustrated-Lewis-pair approach to catalytic reduction of alkynes to cis-alkenes, Nature Chem. 5, 718 (2013)
  • T. A. Rokob, I. Bakó, A. Stirling, A. Hamza, I. Pápai, Reactivity Models of Hydrogen Activation by Frustrated Lewis Pairs: Synergistic Electron Transfers or Polarization by Electric Field?, J. Am. Chem. Soc. 135, 4425 (2013)
  • T. A. Rokob, I. Pápai, Hydrogen Activation by Frustrated Lewis Pairs: Insights from Computational Studies, Top. Curr. Chem. 332, 157 (2013)

3) Transition metal catalyzed C-C coupling reactions

Homogeneous transition metal catalysis is a rapidly expanding field in synthetic chemistry for the construction of new scaffolds or improving routes to previously synthesized molecules. A large number of new synthetic strategies have been developed over the past decades, affording efficient and selective formation and cleavage of carbon-carbon or carbon-heteroatom bonds under mild conditions. These transition metal catalyzed reactions play an important role in natural product synthesis, pharmaceutical and fine chemical industry, in constructing biologically active molecules, and also in large-scale industrial processes. Understanding the mechanism and identification of the key steps are fundamental in improving the catalytic performance and in developing new processes. Computational chemistry can offer an important contribution by providing a detailed atomistic view of the reaction steps together with valuable thermodynamic and kinetic insights.

Transition state of proton-coupled electron transfer as a step of a Pd-catalyzed cross coupling reaction Free energy diagram of a silver-catalyzed C-C coupling

Related papers:

  • Orsolya Tischler, Szabolcs Kovács, Gábor Érsek, Péter Králl, János Daru, András Stirling, Zoltán
    Novák, Study of Lewis Acid Accelerated Palladium Catalyzed C-H Activation, J. Mol. Catal. A 426, 444 (2017)
  • Szabolcs Kovács, Balázs L. Tóth, Gábor Borsik, Tamás Bihari, Nóra V. May, András Stirling, Zoltán Novák, Direct ortho-Trifluoroethylation of Aromatic Ureas by Palladium Catalyzed C-H activation: A Missing Piece of Aromatic Substitutions, Adv. Synth. Catal. 359, 527 (2017)
  • G. L.Tolnai, A. Székely, Z. Makó, T. Gáti, J. Daru, T. Bihari, A. Stirling, Z. Novák, Efficient direct 2,2,2-trifluoroethylation of indoles via C-H functionalization, Chem. Comm., 51, 4488 (2015)
  • A. Jakab, Z. Dalicsek, T. Holczbauer, A. Hamza, I. Pápai, Z. Finta, G. Timári, T. Soós, Superstable Pd(0) Complex as an Air- and Thermostable Catalyst for Suzuki Coupling Reactions, Eur. J. Org. Chem., 2015, 60 (2015)
  • M. V. Leskinen, Á. Madarász, K. T. Yip, A. Vuorinen, I. Pápai, A. J. Neuvonen, P. M. Pihko, Cross-Dehydrogenative Couplings between Indoles and β-Keto Esters: Ligand-Assisted Ligand Tautomerization and Dehydrogenation via a Proton-Assisted Electron Transfer to Pd(II), J. Am. Chem. Soc., 136, 6453 (2014)
  • F. Szabó, J. Daru, D. Simkó, T. Z. Nagy, A. Stirling, Z. Novák, Mild Palladium Catalyzed Oxidative Direct ortho-C-H Acylation of Anilides under Aqueous Conditions, Adv. Synth. Catal., 355, 685 (2013)
  • J. Daru, Z. Benda, A. Poti, Z. Novak, A. Stirling, Mechanistic study of silver-mediated furan formation by oxidative coupling, Chem. Eur. J. 20, 15395 (2014)

4) CO2 chemistry

There is an inceasing interest in the utilization of carbon dioxide as a raw material in environmentally benign processes. CO2 is a readily available, inexpensive and potentially renewable carbon source, but the economical transformation is hindered by its thermodynamical stability. The required input energy is usually provided via high-energy reactants (H2, unsaturated compounds, strained ring compounds, etc.) and the development of efficient catalysts is necessary to make these reactions kinetically feasible.

In collaboration with Prof. Michele Aresta (University of Bari), we investigate the energetic requirements and the mechanisms of reactions leading to organic carbonates.

Dimethyl carbonate product bound to zinc catalyst

Related papers:

  • A. Dibenedetto, A. Angelini, S. Fasciano, Imre Pápai, D. Curulla-Ferré, M. Aresta, The reaction mechanism in the ethanolysis of urea with transition metal-based catalysts: DFT calculations and experiments, J. CO2 Util. 8, 27 (2014)
  • M. Aresta, A. Dibenedetto, A. Angelini, I. Pápai, Reaction Mechanisms in the Direct Carboxylation of Alcohols for the Synthesis of Acyclic Carbonates, Top. Catal. 58, 2 (2015)
  • A. Dibenedetto, F. Nocito, A. Angelini, I. Papai, M. Aresta, R. Mancuso, Catalytic Synthesis of Hydroxymethyl-2-oxazolidinones from Glycerol or Glycerol Carbonate and Urea, ChemSusChem 6, 345 (2013)
  • M. Aresta, A. Dibenedetto, C. Pastore, A. Angelini, B. Aresta, and I. Pápai, Influence of Al2O3 on the performance of CeO2 used as catalyst in the direct carboxylation of methanol to dimethylcarbonate and the elucidation of the reaction mechanism, J. Catal., 269, 44 (2010)

5) Chemistry in aqueous environment

In these projects, we focus on the structural and spectroscopic properties as well as on the reactivity of hydrated molecules and ions. The common motifs of these studies are the simulation tool, namely ab initio MD and the motivation to understand the diverse roles of the solvent water molecules in shaping the chemistry of the solute. In aquous reactions, the solvent H2O molcules usually play dual role: they both stabilize the reaction partners, intermediates and TS structures, and in the same time they participate in the reactions. From modelling point of view the challenge is how to build these roles into the simulations. We employ extended, periodic models for the that also include the solvent water molecules explicitely. In order to incorporate the various entropy effects, we carry out molecular dynamics simulations and employ additional techniques (mostly metadynamics) to observe rare events (such as reactions).

We have recently applied this methodology to study the first steps of the Wacker reaction, and the dissolution of carbon dioxide in neutral or basic environment.

Related papers:

  • I. Bakó, L. Pusztai and L. Temleitner, Decreasing temperature enhances the formation of sixfold hydrogen bonded rings in water-rich water-methanol mixtures, Scientific Reports, 7, 1073 (2017)
  • T. Zhou, A. McCue, Y. Ghadar, I. Bakó and A. E. Clark, Structural and Dynamic Heterogeneity of Capillary Wave Fronts at Aqueous Interfaces, J. Phys. Chem. B., 121, 9052 (2017)
  • A. Stirling, T. Rozgonyi, M. Krack and M. Bernasconi, Prebiotic NH3 formation: insights from simulations, Inorg. Chem., 55, 1934 (2016)
  • A. Stirling, T. Rozgonyi, M. Bernasconi and M. Krack, Pyrite in contact with supercritical water: The desolation of steam, Phys. Chem. Chem. Phys., 17, 17375 (2015)
  • A. Stirling, N. Nair, G. Ujaque, A. Lledos, Challenges in Modelling Homogeneous Catalysis: New Answers from Ab Initio Molecular Dynamics to the Controversy on the Wacker Process, Chem. Soc. Rev., 43, 4940 (2014)
  • A. Stirling, HCO3– Formation from CO2 at High pH: ab Initio Molecular Dynamics Study, J. Phys. Chem. B., 115, 14683 (2011)
  • A. Stirling, I. Pápai, H2CO3 Forms via HCO3- in Water, J. Phys. Chem. B, 114, 16854 (2010)

6) Obtaining chemical information from molecular wave functions

According to the classical picture in chemistry, molecules consist of atoms connected by chemical bonds. Quantum chemical calculations, however, do not refer to atoms, but to particles that make them up, i.e., nuclei and electrons, with the emphasis usually on the latter. Consequently, wave functions describing electronic structures of molecules contain only indirect information about the location and multiplicity of bonds, about energy terms that can be associated with individual bonds, or about other similar information of chemical nature.

The aim of our research, pursued since 1982, is to introduce definitions and devise theoretical methods for the quantification of chemically relevant concepts, which allow the processing of wave functions from a chemical point of view in practice. In this way, useful information can be gathered about specific molecules, and the results can be interpreted also within a classical chemical framework.

Concrete topics in focus include bond order and valence indices, energy components, effective atom and group orbitals, as well as local spins.

I. Mayer: Bond Orders and Energy Components: Extracting Chemical Information from Molecular Wave Functions

Related papers:


  • University of Jyväskylä, Finland
  • University of Helsinki, Finland
  • University of Bari, Italy
  • Universitat Autonoma de Barcelona, Spain
  • University of Girona, Spain
  • Angstrom Laboratory, Uppsala University, Sweden

Educational activities

Supervising PhD students (ELTE Chemistry Doctoral School)

Doctoral courses (ELTE Chemistry Doctoral School)


Imre Pápai


2018-07-25T15:46:37+00:00 2018. April 11.|Research Groups|