Boosting Anion Transport Activity of Diamidocarbazoles by Electron Withdrawing Substituents.

Frontiers in Chemistry
Krystyna Maslowska-JarzynaMichał J Chmielewski

Abstract

Artificial chloride transporters have been intensely investigated in view of their potential medicinal applications. Recently, we have established 1,8-diamidocarbazoles as a versatile platform for the development of active chloride carriers. In the present contribution, we investigate the influence of various electron-withdrawing substituents in positions 3 and 6 of the carbazole core on the chloride transport activity of these anionophores. Using lucigenin assay and large unilamellar vesicles as models, the 3,6-dicyano- and 3,6-dinitro- substituted receptors were found to be highly active and perfectly deliverable chloride transporters, with EC50,270s value as low as 22 nM for the Cl-/NO3 - exchange. Mechanistic studies revealed that diamidocarbazoles form 1:1 complexes with chloride in lipid bilayers and facilitate chloride/nitrate exchange by carrier mechanism. Furthermore, owing to its increased acidity, the 3,6-dinitro- substituted receptor acts as a pH-switchable transporter, with physiologically relevant apparent pKa of 6.4.

References

Feb 1, 2007·Chemical Society Reviews·Anthony P DavisBradley D Smith
Oct 28, 2009·IUBMB Life·Wei-Qun Ding, Stuart E Lind
Aug 19, 2011·Journal of the American Chemical Society·Nathalie BusschaertPhilip A Gale
Mar 29, 2013·Accounts of Chemical Research·Francesco De RiccardisPaolo Tecilla
Dec 18, 2013·Chemical Communications : Chem Comm·Krzysztof M Bąk, Michał J Chmielewski
Aug 15, 2014·Journal of the American Chemical Society·Hennie ValkenierAnthony P Davis
Dec 30, 2014·Acta Crystallographica. Section A, Foundations and Advances·George M Sheldrick
Jan 9, 2015·Acta Crystallographica. Section C, Structural Chemistry·George M Sheldrick
May 23, 2015·Chemical Communications : Chem Comm·Robert B P ElmesKatrina A Jolliffe
Jul 7, 2015·Chemical Science·Nathalie BusschaertPhilip A Gale
Aug 12, 2015·Chemical Communications : Chem Comm·Hennie ValkenierAnthony P Davis
Dec 18, 2015·Nature Chemistry·Hongyu LiAnthony P Davis
May 26, 2016·Journal of the American Chemical Society·Tanmoy SahaPinaki Talukdar
Jun 15, 2016·Journal of the American Chemical Society·Ethan N W HowePhilip A Gale
Apr 6, 2017·Chemical Society Reviews·Philip A GaleRoberto Quesada
Mar 1, 2016·Chemical Science·Nestor Lopez MoraAlexander Kros
Jan 30, 2018·Organic & Biomolecular Chemistry·Christopher M DiasAnthony P Davis
Mar 2, 2018·Chemistry : a European Journal·Christopher M DiasAnthony P Davis
Jul 5, 2018·Organic & Biomolecular Chemistry·Krzysztof M BąkMichał J Chmielewski
Sep 29, 2018·Cancers·Vivek KaushikAnand K V Iyer
Mar 30, 2019·Angewandte Chemie·Glenn GrauwelsKristin Bartik
May 29, 2019·Organic & Biomolecular Chemistry·Abhishek SahaDebasis Manna
Apr 3, 2020·Chemical Communications : Chem Comm·Krzysztof M BąkMichał J Chmielewski
Jul 22, 2020·Chemical Society Reviews·Jeffery T DavisRoberto Quesada
Aug 20, 2020·Chemical Communications : Chem Comm·Giacomo PicciClaudia Caltagirone

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Citations

Jun 3, 2021·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Krystyna Maslowska-JarzynaMichał J Chmielewski

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