Copper(II) сomplexes with 2-hydrохy-5-ethylphenylphosphosphonic acid: synthesis, structure, cytotoxicity, and accumulation in HeLa cells

Abstract

In order to study the physicochemical and biological properties of the coordination compounds of bioactive metal ions with 2-hydroxyphenylphosphonic acid derivatives, the reaction of 2-hydroxy-5-ethylphenylphosphonic acid (Н3L1) with copper(II) perchlorate, sulfate, nitrate, and acetate in water was studied for the first time. It has been established that, regardless of the ratio of reagents, in the case of copper(II) perchlorate, sulfate, and nitrate, a complex of the composition [Cu(H2L1)2(Н2О)2] is formed in high yield, while in the case of using copper(II) acetate a complex [Cu(HL1)(H2O)2] is formed, the composition of which is established on the basis of a combination of elemental analysis data, IR and electronic spectra. Quantum-chemical calculations of the structure of [Cu(H2L1)2(H2O)2] and [Cu(HL1)(H2O)2] complexes were performed for the first time by the density functional theory (DFT) method. The cytotoxic properties of H3L1 acid and copper complexes [Cu(HL1)(H2O)2] and [Cu(H2L1)2(H2O)2] with respect to HeLa tumor cells of human cervical adenocarcinoma were studied. The accumulation of the resulting copper(II) complexes in HeLa cells was proved by laser confocal microscopy.