Thio-Functionalized β-Cyclodextrin as a Metal-Binding Therapeutic Scaffold: Coordination with Co (II)/Cu (II), Antibacterial Activity, and in Silico Evaluation for Biomedical Use.

This paper describes a new approach to the synthesis and design of mono-6-deoxy-(m-acetophenonethio)-β-cyclodextrin, a novel thio-functionalized β-cyclodextrin-based ligand. The ligand effectively complexed with Cu(II) and Co(II) ions to produce two complexes that were soluble in water. Through structural characterization using FT-IR, UV-visible spectroscopy, ¹H NMR, and MS, it was discovered to have a 1:1 stoichiometry of metal to ligand and a tetra-coordinated geometry. Further investigation of the complexes' electronic structure, stability, and optimized geometries was carried out using Density Functional Theory (DFT) calculations, which showed that the electronic characteristics agreed with experimental results. The in vitro anti-microbial activity of the free ligand and its metal complexes was assessed against various Gram-positive and Gram-negative bacterial strains. Additional evidence for the reported biological activity came from molecular docking simulations that revealed advantageous interactions with significant bacterial proteins that suggested possible mechanisms of action. This work opens the door for the creation of bioactive cyclodextrin-metal complexes by tying coordination chemistry/ coordination, and theoretical investigations to supramolecular ligand design principles.