Design and Electrochemical Investigation of Ureido-Sulfonamidic Receptors for Phosphates
Authors: Salvadori Karolína , Cuřínová Petra , Šimková Ludmila , Ludvik Jiri , Matějka Pavel 
Published: July 2021

Anions play an important role in biological systems. At the same time, many of them are the major environmental pollutants and substances endangering living organisms [1]. For these purposes the anion recognition, elimination and sensing would find application in many branches including application in medicine or environmental chemistry. Suitable examples of anion pollutants are phosphates, which could cause eutrophication of water and they are also known for their limited removal from body fluids, which could lead to serious health problems. Therefore, the aim of our research group is the design and preparation of anionic receptors with suitable binding sites to bind these anions.

In the first step of our synthesis a series of substituted nosylamidic intermediates (fig. a, b) was prepared. These substances are suitable precursors for the synthesis of novel receptors bearing ureido functions (fig. c). The sulfonamidic motif itself is known as a neutral donor of hydrogen bond. Hence for better understanding of the behaviour of the final urea receptors, the properties of intermediate molecules were studied by various physicochemical techniques including spectroscopic and electrochemical methods.

Spectroscopic methods were used to evaluate the binding ability of this motif and to determine its acid-basic properties. Electrochemical methods (represented by polarography and cyclic voltammetry with mercury dropping or hanging electrodes in dimethylformamide with Bu4N PF6 as electrolyte) were chosen because the nitro groups in our intermediate molecules are not only important substituents enabling continuation in synthesis, but also electrochemical "probes" reflecting the properties of the parent molecule. Their reduction in aprotic media is generally known after the first one-electron reversible reduction step where a stable radical anion is formed, a three-electron irreversible process follows resulting in the corresponding hydroxylamine [2]. However, the reduction pattern of the series (b) is totally different: After the first irreversible step (theoretically involving 4/5 of electron) a one-electron reversible reduction takes place followed by a multielectron process. This behaviour can be explained by using autoprotonation mechanism [3] where the acidic hydrogen of the sulfonamidic group is involved.

Then our attention focused on final receptors (fig c). It was shown, that sulfonamidic moiety can be utilized as an electron-withdrawing group useful to enhance the anion complexation properties of urea-based receptors. On the other hand, it brings an inherent predisposition for deprotonation in the presence of more basic anions. In order to shift the deprotonation/complexation equilibrium in favour of the complexation, the receptors were derivatized by electron-donating groups like –OCH3 at sulfonamidic moiety. The binding for this receptor was evaluated in a competitive solvent (DMSO) by using NMR titration experiments. The experimental results show a considerable selectivity of our receptor to phosphates compared to another biologically important anions such as Cl-, NO3
- and HSO4
- [4].

Based on these results, the prepared receptors appear to be suitable motifs for binding phosphate anions. In order to take advantage of their binding capabilities, these molecules need to be attached to the surface of a suitable molecular carrier. The formation of these functional materials (in our case especially dendrimers) is also associated with the need to design and optimize methods to describe anion binding ability, as well as the possibility to recycle the prepared materials. This was the reason for which it seems to be interesting to consider the presence of an electrochemical “probe” also in the final molecular receptors. The redox transformation of such a probe should fundamentally affect the complexing abilities of the receptor and allow targeted degradation of the complex.

Acknowledgements: The work was supported by the grant number 18-12150S and 20-07833S.

References:

[1] A J. L. Sessler, P. A. Gale and W. S. Cho in Anion Receptor Chemistry, The Royal Soc. Of Chemistry, Cambridge, 2006.

[2] a) O. Exner, A critical compilation of substituent constants, in: N.B. Chapman, J. Shorter (Eds.), Correlation Analysis in Chemistry, Plenum Press, N.Y. London, 1978, pp. 445. b) P. Zuman, Subsituent Effects in Organic Polarography, Plenum Press, New York, 1967.

[3] E. Brillas, G. Farnia, M. G. Severin, E. Vianello; Electrochimica Acta 31 (1986) 759-766.

[4] K. Salvadori, L. Šimková, I. Císařová, J. Sýkora, J. Ludvík, P. Cuřínová, Sulphonamidic groups as electron‐withdrawing units in ureido‐based anion receptors: enhanced anion complexation versus deprotonation. ChemPlusChem 2020, 85 (7), 1401–1411.

Figure 1