Peptidomimetics based on pillar[5]arene: Charge effect on self-assembly, toxicity, and herbicide binding

Abstract

Contact herbicides are widely used if rapid weeds eradication is required despite of a number of inherent disadvantages (transfer to water and soil, damage of non-target plants, promotion of resistant weeds expansion, etc.). Supramolecular chemistry can solve the problems associated with herbicide degradation and spreading, as well as suppress their harmful effects on humans and the environment. Pillar[n]arene derivatives are of special interest among other macrocyclic platforms due to their ability to implement various substrates in the macrocycle cavity. However, most of the works devoted to the interaction of pillararenes with pesticides considers binding of paraquat and its derivatives. In this work, water soluble derivatives of pillar[5]arene containing L-tryptophan residues have been proposed for binding a range of herbicides including paraquat dichloride, pyridate, 3-(methylphosphinico)propionic acid, and glufosinate-ammonium. The ester derivative of pillar[5]arene was found to be able to bind the above species. The betaine derivative showed selective and efficient interaction with pyridate (logKa = 4.02) and paraquat (logKa = 3.17). The effect of the charge of the pillar[5]arene substituent on the toxicity of the macrocyclic platform towards A549 and LEK cell lines was demonstrated. Introduction of carboxylate functions to form betaine fragments compensated for the positive charge of the macrocycle substituent and decreased its toxicity by three orders of magnitude for A549 cell line (167.0 μM), and by two orders of magnitude for LEK cells (56.0 μM) compared to ester derivative of pillar[5]arene (3.1 and 3.6 μM respectively). The results obtained confirmed the prospects of the use of amino acid derivatized pillar[5]arenes in the development of new approaches to the removal of the herbicides from the environment that are demanded both in agriculture and aquaculture.