A DFT/PCM Study on the Affinity of Salinomycin to Bind Monovalent Metal Cations.

Todor Dudev,Diana Cheshmedzhieva,Ivayla Pantcheva,Peter Dorkov

doi:10.3390/molecules27020532

Todor Dudev, Diana Cheshmedzhieva + Show 2 more

Open Access

https://doi.org/10.3390/molecules27020532

Copy DOI

Abstract

The affinity of the polyether ionophore salinomycin to bind IA/IB metal ions was accessed using the Gibbs free energy of the competition reaction between SalNa (taken as a reference) and its rival ions: [M+-solution] + [SalNa] → [SalM] + [Na+-solution] (M = Li, K, Rb, Cs, Cu, Ag, Au). The DFT/PCM computations revealed that the ionic radius, charge density and accepting ability of the competing metal cations, as well as the dielectric properties of the solvent, have an influence upon the selectivity of salinomycin. The optimized structures of the monovalent metal complexes demonstrate the flexibility of the ionophore, allowing the coordination of one or two water ligands in SalM-W1 and SalM-W2, respectively. The metal cations are responsible for the inner coordination sphere geometry, with coordination numbers spread between 2 (Au+), 4 (Li+ and Cu+), 5/6 (Na+, K+, Ag+), 6/7 (Rb+) and 7/8 (Cs+). The metals’ affinity to salinomycin in low-polarity media follows the order of Li+ > Cu+ > Na+ > K+ > Au+ > Ag+ > Rb+ > Cs+, whereas some derangement takes place in high-dielectric environment: Li+ ≥ Na+ > K+ > Cu+ > Au+ > Ag+ > Rb+ > Cs+.

Highlights

Laboratory of Computational Chemistry and Spectroscopy, Faculty of Chemistry and Pharmacy, Laboratory of Biocoordination and Bioanalytical Chemistry, Faculty of Chemistry and Pharmacy
Salinomycin is a polyketide ionophore extracted from Streptomyces albus [1]
The metal(I)-loaded constructs of salinomycin were modeled according to the only available crystal structures of sodium salinomycinate (SalNa) [31]

Summary

Introduction

Laboratory of Computational Chemistry and Spectroscopy, Faculty of Chemistry and Pharmacy, Laboratory of Biocoordination and Bioanalytical Chemistry, Faculty of Chemistry and Pharmacy,. The biological activity of salinomycin is primarily based on its ability to form lipophilic complexes with the monovalent alkaline ions, making the membranes of target cells permeable to the ions mentioned. In this way, the intracellular cation concentration in the cells is disturbed, leading to a cascade of energy-consuming processes and ultimate cell death. The weak interaction (H-bond formation) between the carboxylic and hydroxyl groups placed on the opposite ends of the molecule causes folding of the structure with the formation of a hydrophilic cavity due to the internally placed polyether oxygen atoms This core is able to accommodate water molecules (SalH) or monovalent

Objectives

Methods

Results

Conclusion