Probing Polar-π Interactions Between Tetrazoles and Aromatic Rings.

Autor: Jian J; Department of Physics, Chemistry and Pharmacy, University of Southern Denmark, Campusvej 55, 5230, Odense, Denmark., Hammink R; Division of Immunotherapy, Oncode Institute, Radboud University Medical Center, Geert Grooteplein 26, 6525 GA, Nijmegen, The Netherlands.; Department of Medical BioSciences, Radboud University Medical Center, Geert Grooteplein 26, 6525 GA, Nijmegen, The Netherlands., Tinnemans P; Institute for Molecules and Materials, Radboud University, Heyendaalseweg 135, 6525 AJ, Nijmegen, The Netherlands., Bickelhaupt FM; Institute for Molecules and Materials, Radboud University, Heyendaalseweg 135, 6525 AJ, Nijmegen, The Netherlands.; Department of Theoretical Chemistry, Amsterdam Center for Multiscale Modeling, Vrije Universiteit Amsterdam, De Boelelaan 1083, 1081 HV, Amsterdam, The Netherlands.; Department of Chemical Sciences, University of Johannesburg, Auckland Park, Johannesburg, 2006, South Africa., Poater J; ICREA, Passeig Lluís Companys 23, 08010, Barcelona, Spain.; Departament de Química Inorgànica i Orgànica & IQTCUB, Universitat de Barcelona, Martí i Franquès 1-11, 08028, Barcelona, Spain., Mecinović J; Department of Physics, Chemistry and Pharmacy, University of Southern Denmark, Campusvej 55, 5230, Odense, Denmark.
Jazyk: angličtina
Zdroj: Chemistry, an Asian journal [Chem Asian J] 2023 May 16; Vol. 18 (10), pp. e202300192. Date of Electronic Publication: 2023 Apr 26.
DOI: 10.1002/asia.202300192
Abstrakt: The heterocyclic tetrazole, a well-established bioisosteric replacement of carboxylic acid, plays an important role in medicinal chemistry. To deepen the functional understanding of tetrazoles in chemical sciences, it is essential to investigate the noncovalent interactions between the tetrazole ring and aromatic rings. Here, we report synthetic, spectroscopic, structural and quantum chemical analyses on specially designed 2-arylphenyl-1H-tetrazoles to study the underlying noncovalent interactions between the tetrazole ring and the neighboring aromatic ring possessing substituents at para/meta position. pK a values and proton affinities of 2-arylphenyl-1H-tetrazoles correlate well with Hammett sigma values of para-substituents at the flanking aromatic ring. Molecular orbital and energy decomposition analyses reveal that through-space NH-π interactions and π-π interactions contribute to the trend of pK a values and proton affinities of 2-arylphenyl-1H-tetrazoles. The electrostatic interaction between tetrazole/tetrazolide interacting with the aromatic rings appears responsible for the observed acidity trends. These results will be helpful for the rational design of tetrazole-based drugs and materials.
(© 2023 The Authors. Chemistry - An Asian Journal published by Wiley-VCH GmbH.)
Databáze: MEDLINE
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