pH-Regulated anion transport activities of bis(iminourea) derivatives across the cell and vesicle membrane

Saha, Abhishek; Akhtar, Nasreen; Kumar, Vishnu; Kumar, Suresh; Srivastava, H. K.; Kumar, Sachin; Manna, Debasis

doi:10.1039/c9ob00650h

Cited by 37 publications

(57 citation statements)

References 38 publications

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“…Since cancer cells are generally associated with lower pH values than healthy cells, it would be very beneficial if synthetic transporters could effectively switch ON in acidic environment and OFF at neutral pH. To date, however, there are only few reports on pH-dependent transporters ( Busschaert et al, 2014 ; Elmes et al, 2015 ; Howe et al, 2016 ; Saha et al, 2019 ; Wang et al, 2021 ) and highly active carriers that possess very specific pH-regulated ON/OFF function are still unavailable.…”

Section: Resultsmentioning

confidence: 99%

“…Among other polar solutes, chloride transport is gaining increasing interest in recent years due to the growing appreciation of its physiological importance (Pusch, 2007). Chloride is the most abundant anion in the extracellular fluids, where its concentration typically exceeds 100 mM (Davis et al, 2007).…”

Section: Introductionmentioning

confidence: 99%

“…The resulting chloride concentration gradients are important physiological parameters and in living cells they are precisely controlled by specialized proteins: pumps, channels and carriers. The transmembrane chloride transport they provide is important for CO 2 excretion and pH regulation, neural signaling and maintaining cell volume (Pusch, 2007). Mutations in genes coding for these proteins are responsible for severe diseases, such as cystic fibrosis (Sheppard et al, 1993;Welsh and Smith, 1993), Bartter syndrome (Simon et al, 1996;Simon et al, 1997), and Dent's disease (Lloyd et al, 1996).…”

Section: Introductionmentioning

confidence: 99%

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Boosting Anion Transport Activity of Diamidocarbazoles by Electron Withdrawing Substituents

2021

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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.

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Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Boosting Anion Transport Activity of Diamidocarbazoles by Electron Withdrawing Substituents

2021

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“…Owing to their very high hydrogen bond donating abilities, combined with their relatively high Brønsted acidities, diamidocarbazoles similar to 3 and 4 may be applicable in organocatalysis [ 37 ] or pH-switchable anion transport through lipophilic membranes [ 38 , 39 , 40 , 41 ]. Research in these directions is ongoing in our laboratories and will be published in due course [ 42 ].…”

Section: Discussionmentioning

confidence: 99%

Carbazole-Based Colorimetric Anion Sensors

et al. 2021

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Owing to their strong carbazole chromophore and fluorophore, as well as to their powerful and convergent hydrogen bond donors, 1,8-diaminocarbazoles are amongst the most attractive and synthetically versatile building blocks for the construction of anion receptors, sensors, and transporters. Aiming to develop carbazole-based colorimetric anion sensors, herein we describe the synthesis of 1,8-diaminocarbazoles substituted with strongly electron-withdrawing substituents, i.e., 3,6-dicyano and 3,6-dinitro. Both of these precursors were subsequently converted into model diamide receptors. Anion binding studies revealed that the new receptors exhibited significantly enhanced anion affinities, but also significantly increased acidities. We also found that rear substitution of 1,8-diamidocarbazole with two nitro groups shifted its absorption spectrum into the visible region and converted the receptor into a colorimetric anion sensor. The new sensor displayed vivid color and fluorescence changes upon addition of basic anions in wet dimethyl sulfoxide, but it was poorly selective; because of its enhanced acidity, the dominant receptor-anion interaction for most anions was proton transfer and, accordingly, similar changes in color were observed for all basic anions. The highly acidic and strongly binding receptors developed in this study may be applicable in organocatalysis or in pH-switchable anion transport through lipophilic membranes.

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“…Owing to their very high hydrogen bond donating ability combined with relatively high Bronsted acidity, diamidocarbazoles similar to 3 and 4 may find applications in, for example, organocatalysis [33] or in pH-switchable anion transport through lipophilic membranes [34][35][36][37]. Research in these directions is ongoing in our laboratories and will be published in due course.…”

Section: Discussionmentioning

confidence: 99%

Carbazole-Based Colorimetric Anion Sensors

Maslowska-Jarzyna¹,

Korczak²,

Wagner³

et al. 2021

Preprint

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Endowed with strong carbazole chromophore and fluorophore as well as with powerful and convergent hydrogen bond donors, 1,8-diaminocarbazoles are amongst the most attractive and synthetically versatile building blocks for the construction of anion receptors, sensors and transporters. Aiming at the development of carbazole-based colorimetric anion sensors, we describe here the synthesis of 1,8-diaminocarbazoles substituted with strongly electron-withdrawing substituents: 3,6-dicyano and 3,6-dinitro. Both of these precursors were subsequently converted into model diamide receptors. Anion binding studies revealed that the new receptors show greatly enhanced anion affinity, but also significantly increased acidity. We found also that rear substitution of 1,8-diamidocarbazole with two nitro groups shifts its absorption spectrum to the visible region and converts receptor into colorimetric anion sensor. The new sensor produces vivid changes in colour and fluorescence upon addition of basic anions in wet DMSO, but is poorly selective: due to its greatly enhanced acidity, for most anions the dominant receptor-anion interaction is proton transfer and, accordingly, similar changes in colour can be observed for every basic anion. The highly acidic and strongly binding receptors developed in this study may find applications in organocatalysis or in pH-switchable anion transport through lipophilic membranes.

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pH-Regulated anion transport activities of bis(iminourea) derivatives across the cell and vesicle membrane

Abstract: pH regulates the transmembrane transport of Cl− ions by bis(iminourea) derivatives.

Cited by 37 publications

References 38 publications

Boosting Anion Transport Activity of Diamidocarbazoles by Electron Withdrawing Substituents

Boosting Anion Transport Activity of Diamidocarbazoles by Electron Withdrawing Substituents

Carbazole-Based Colorimetric Anion Sensors

Carbazole-Based Colorimetric Anion Sensors

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