The bioisosteric similarity of the tetrazole and carboxylate anions: clues from the topologies of the electrostatic potential and of the electron density

European Journal of Medicinal Chemistry
Chérif F MattaDonald F Weaver

Abstract

There is a need for an a priori method with which to demonstrate the physical similarities between non-classical bioisosteres. In this study we explore the utility of the electron density and the electrostatic potential as the basis for a systematic investigation of the physical and chemical similarities between bioisosteres. The tetrazole and carboxylate bioisosteric pair is used as an illustrative example. It is shown that tetrazole and carboxylate anions give rise to electrostatic potentials (ESP) that exhibit a remarkable local similarity in the disposition of four coplanar local minima at positions consistent with lone pairs. The similarity of the disposition of these ESP minima generated by the two bioisosteres is in sharp contrast with their differences in the number and types of atoms, their nuclear geometrical arrangements, their total volumes, their partial charges, and their electron populations. The topology and geometrical disposition of these minima are shown to be independent of the capping group used in the model, and thus an inherent property of this bioisosteric pair. A model of the receptor region responsible for binding to either of these bioisosteres is proposed on the basis of an electrostatic "lock-and-key".

References

Jan 1, 1999·Bioorganic & Medicinal Chemistry Letters·W W MederskiC Wilm
Sep 15, 1988·Physical Review A: General Physics·A D Becke

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Citations

Jan 10, 2012·ACS Chemical Biology·Kristin E FinchPaul J Hergenrother
Mar 13, 2016·Bioorganic & Medicinal Chemistry·Zheng LiuAlicia Regueiro-Ren
Mar 16, 2016·Future Medicinal Chemistry·Alya A Arabi, Chérif F Matta
Mar 12, 2016·Journal of Medicinal Chemistry·Pierrik LassalasCarlo Ballatore
Jun 4, 2016·Journal of Molecular Graphics & Modelling·Abdolkarim FarrokhzadehAli Ebrahimi
Jun 29, 2016·ACS Chemical Biology·Tyler D HuberJon S Thorson
Jun 24, 2020·Molecular Informatics·Dominique Douguet, Frédéric Payan
Jul 22, 2020·Future Medicinal Chemistry·Hrvoje RimacVladimir A Potemkin
Jan 17, 2013·ChemMedChem·Christian B M Poulie, Lennart Bunch
Feb 17, 2017·Dalton Transactions : an International Journal of Inorganic Chemistry·Lars H FingerJörg Sundermeyer
Dec 7, 2013·Chemistry : a European Journal·Lukasz AlbrechtKarl Anker Jørgensen
Nov 10, 2017·Future Medicinal Chemistry·Alya A Arabi
Nov 12, 2020·Organic & Biomolecular Chemistry·Huang-Chi DuYing-Chu Chen
Jul 3, 2021·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Nadezhda PalkoVladimir Potemkin
Dec 17, 2011·The Journal of Organic Chemistry·Andriy V TymtsunikIgor V Komarov
Feb 2, 2019·Chemical Reviews·Constantinos G NeochoritisAlexander Dömling

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