Theoretical investigation of microcystin-LR, microcystin-RR and nodularin-R complexation with α-, β-, and γ-cyclodextrin as a starting point for the targeted design of efficient cyanotoxin traps

Abstract

The interactions of three abundant cyanotoxins, namely microcystin-LR, microcystin-RR and nodularin-R with α-, β-, and γ-cyclodextrin in water were structurally and thermodynamically investigated by a computationally affordable methodology using the semi-empirical PM7 method in conjunction with an implicit treatment of solvent effects by the conductor-like screening model (COSMO). As an in silico methodology, PM7(COSMO) offers the advantage of being more environment-friendly than experimental approaches, provided that its computational accuracy limitations are properly accounted for. The results suggest the formation of 1:1 complexes via partial inclusion of the hydrophobic side-chain of cyanotoxins inside the cyclodextrin cavity preferably via the wider opening, further stabilized by hydrogen bonds between hydrophilic groups of the interacting molecules. Enthalpy and entropy changes upon complexation result in a binding efficiency increasing with cyclodextrin size, along with an increase dependent on cyanotoxin, in the order nodularin-R<microcystin-RR<microcystin-LR. The calculated binding efficiency trends are in accordance with literature experimental results demonstrating the reliability and utility of the PM7(COSMO) level of theory in modeling the interactions of cyanotoxins with cyclodextrins. In addition, the method has the ability to describe the structural features of the complexes. Therefore, it may be considered as a valuable computational tool for the targeted design of efficient cyanotoxin filtration agents utilizing cyclodextrin derivatives. The environmental benefits from the theoretical screening of non-toxic carbohydrate macrocycles as effective scavengers of harmful cyanotoxins satisfy the growing demand for sustainable chemistry solutions to practical problems of worldwide significance.