Design, synthesis and application of carbazole macrocycles in anion sensors

Abstract

Carboxylate sensing solid-contact ion-selective electrodes (ISEs) were created to provide a proof-of-concept ISE development process covering all aspects from in silico ionophore design to functional sensor characterization. The biscarbazolylurea moiety was used to synthesize methylene-bridged macrocycles of different ring size aiming to fine tune selectivity towards different carboxylates. Cyclization was achieved with two separate strategies, using either amide synthesis to access up to –[CH2]10– macrocycles or acyl halides to access up to –[CH2]14– macrocycles. Seventy-five receptor–anion complexes were modelled and studied with COSMO-RS, in addition to all free host molecules. In order to predict initial selectivity towards carboxylates, 1H NMR relative titrations were used to quantify binding in DMSO-d 6/H2O solvent systems of two proportions – 99.5%:0.5% m/m and 90.0%:10.0% m/m, suggesting initial selectivity towards acetate. Three ionophores were selected for successful sensor prototype development and characterization. The constructed ion-selective electrodes showed higher selectivity towards benzoate than acetate, i.e., the selectivity patterns of the final sensors deviated from that predicted by the classic titration experiments. While the binding constants obtained by NMR titration in DMSO-d 6/H2O solvent systems provided important guidance for sensor development, the results obtained in this work emphasize the importance of evaluating the binding behavior of receptors in real sensor membranes.

Carbazole-Based Colorimetric Anion Sensors

“…It combines several attractive features, such as the presence of a strong carbazole chromophore and fluorophore directly coupled with anion binding sites, a strong hydrogen bond donor (i.e., carbazole NH), a rigid skeleton that facilitates the preorganization of auxiliary hydrogen bond donors and the ease of synthesis and derivatization. Diaminocarbazole-based receptors show particularly high affinity towards oxyanions (carboxylates, phosphates, and sulfates) [ 3 , 11 , 12 , 13 , 14 , 15 , 16 , 17 , 18 , 19 , 20 , 21 , 22 , 23 , 24 ] and some of them are also very active anion transporters [ 22 , 25 , 26 ].…”

Carbazole-Based Colorimetric Anion Sensors

“…It combines several attractive features, such as the presence of a strong carbazole chromophore and fluorophore directly coupled with anion binding sites, strong hydrogen bond donor -carbazole NH, rigid skeleton that facilitates preorganization of auxiliary hydrogen bond donors and the ease of synthesis and derivatization. Diaminocarbazole-based receptors show particularly high affinity towards oxyanions (carboxylates, phosphates and sulphates) [3,[11][12][13][14][15][16][17][18][19][20][21][22][23][24] and some of them are also very active anion transporters [22,[25][26].…”

Potentiometric Carboxylate Sensors Based on Carbazole-Derived Acyclic and Macrocyclic Ionophores

“…Many inorganic cationic analytes (e.g., H + , Na + , K + , Cu 2+ , Pb 2+ ) have receptors that can be used to prepare ISMs with good or even excellent selectivity [12]. However, there are many anionic analytes that are of great importance in, e.g., clinical chemistry, and, as such, the field of anion receptors has received a great deal of attention in the last two decades [15][16][17][18][19][20][21][22][23][24][25][26][27][28][29][30]. Many new anion receptors are published each year, but unfortunately, in the vast majority of cases, these receptors do not make the leap from binding studies to sensor prototyping, let alone practical use.…”

“…In the present work, four derivatives of 1,3-bis(carbazolyl)urea (Figure 1) were systematically studied as anion receptors in SC-ISEs. These receptors were originally designed in silico and were recently found to be promising as ionophores for acetate and other carboxylates [30,31]. Here, ISEs based on these four anion receptors were prepared and investigated.…”

“…The receptors included three macrocyclic receptors (Figure 1a) and an acyclic receptor (Figure 1b). The chosen receptors had previously only been used to prepare ISEs with a single membrane composition [30,31]. In this work, the influences of the plasticizer and the material of the electrode body were studied systematically for each anion receptor.…”