Through-Space Stabilization of an Imidazolium Cation by Aromatic Rings
- Jie JianJie JianDepartment of Physics, Chemistry and Pharmacy, University of Southern Denmark, Campusvej 55, 5230 Odense, DenmarkMore by Jie Jian
- Darina BarkhatovaDarina BarkhatovaDepartment of Physics, Chemistry and Pharmacy, University of Southern Denmark, Campusvej 55, 5230 Odense, DenmarkMore by Darina Barkhatova
- Roel HamminkRoel HamminkDivision of Immunotherapy, Oncode Institute, Radboud University Medical Center, Geert Grooteplein 26, 6525 GA Nijmegen, The NetherlandsDepartment of Tumor Immunology, Radboud Institute for Molecular Life Sciences, Radboud University Medical Center, Geert Grooteplein 26, 6525 GA Nijmegen, The NetherlandsMore by Roel Hammink
- Paul TinnemansPaul TinnemansInstitute for Molecules and Materials, Radboud University, Heyendaalseweg 135, 6525 AJ Nijmegen, The NetherlandsMore by Paul Tinnemans
- F. Matthias BickelhauptF. Matthias BickelhauptInstitute for Molecules and Materials, Radboud University, Heyendaalseweg 135, 6525 AJ Nijmegen, The NetherlandsDepartment of Theoretical Chemistry, Amsterdam Center for Multiscale Modeling, Vrije Universiteit Amsterdam, De Boelelaan 1083, 1081 HV Amsterdam, The NetherlandsMore by F. Matthias Bickelhaupt
- Jordi Poater*
- , and
- Jasmin Mecinović*
Imidazole-based compounds are widely found in natural products, synthetic molecules, and biomolecules. Noncovalent interactions between the imidazole ring and other functional groups play an important role in determining the function of diverse molecules. However, there is a limited understanding of the underlying noncovalent interactions between imidazoles and aromatic systems. In this work, we report physical-organic chemistry studies on 2-(2,6-diarylphenyl)-1H-imidazoles and their protonated forms to investigate the noncovalent interactions between the central imidazole ring and two flanking aromatic rings possessing substituents at the para/meta position. Hammett analysis revealed that pKa values and proton affinities correlate well with Hammett σ values of para-substituents at the flanking rings. Additional quantitative Kohn–Sham molecular orbital and energy decomposition analyses reveal that through-space π–π interactions and NH−π interactions contribute to the intramolecular stabilization of the imidazolium cation. The results are important because they clearly demonstrate that the imidazolium cation forms energetically favorable noncovalent interactions with aromatic rings via the through-space effect, a knowledge that can be used in rational drug and catalyst design.
This article has not yet been cited by other publications.