What are the prospects for using complexes of copper(ii) and zinc(ii) to suppress the vital activity of Mycolicibacterium smegmatis?

Irina A Lutsenko,Yulia V Nelyubina,Igor L Eremenko,Yulia K Voronina,Veronika V Garaeva,Mikhail A Kiskin,Valery N Danilenko,Teimur M Aliev,Petr V Primakov,Olga B Bekker,Dmytry A Aleshin,Dmitry E Baravikov,Kseniya A Koshenskova

doi:10.1039/d1ra08555g

Abstract

New complexes of zinc(ii) and copper(ii) with 2-furoic acid (Hfur), acetic acids and N-donor ligands with the compositions [Zn2(fur)4]n (1), [Zn2(fur)4(NH2py)2] (2, NH2py = 3-aminopyridine), [Zn(fur)2(neoc)] (3, neoc = 2,9-dimethyl-1,10-phenantroline), [Zn(OAc)2(neoc)] (4, OAc = acetat-anion), and [Cu(fur)2(neoc)(H2O)] (5) were synthesized. The structures of the compounds were established by single crystal X-ray diffraction analysis. Complexes 1 and 2 are binuclear; whereas 3–5 are mononuclear. The stabilization of supramolecular architectures in crystals for compounds 1–5 occurs due to π–π-bonding between heterocycles and hydrogen interactions that provide good solubility in aqueous solutions. The stability of the complexes upon dissolution in 5% dextrose and 0.9% NaCl was confirmed by UV-vis spectroscopic and NMR (1H) data. The study of in vitro biological activity was carried out against the non-pathogenic strain of Mycolicibacterium smegmatis that is a model for M. tuberculosis. The synergistic effect of ligands is observed for complexes 3–5 and is characterized by an increase in the biological activity values. On passage from Zn2+ to Cu2+ complexes, the biological activity increases and the maximum effect is observed for compound [Cu(fur)2(phen)]. Analysis of the transcriptomic profiles of the M. smegmatis mc2155 strain under the pressure of the copper complex [Cu(fur)2(phen)] made it possible to isolate 185 genes, one quarter of which are associated with the compensation of iron deficiency in the bacterial strain. Genes associated with the transport and metabolism of heavy metals, biosynthesis of fatty and amino acids, biodegradation and transport of urea were also isolated.

Highlights

Tuberculosis is among the most hazardous diseases of mankind and takes the lives of tens of thousands of people every year.1 More than 130 years have passed since the discovery of the tuberculosis pathogen by R
All the complexes are readily soluble in water and show stability according to NMR (1H) data upon dissolution in DMSO solutions, as well as in glucose and NaCl solutions according to UV-vis results
The in vitro biological activity of the complexes against the model non-pathogenic strain M. smegmatis showed the lowest activity of polymeric complex 1

Summary

Introduction

Tuberculosis is among the most hazardous diseases of mankind (according to the WHO) and takes the lives of tens of thousands of people every year.1 More than 130 years have passed since the discovery of the tuberculosis pathogen by R. Compounds 3 (Fig. 4a) and 4 (Fig. 4b) have a very similar molecular structures (Table 1) with the zinc ion binding one neoc ligand (Zn–N 2.057(2)–2.102(3) A) and two furÀ or AcÀ anions (Zn–O 1.9485(18)–1.976(2) and 1.911(3)–2.43(3) A) that coordinate it in a monodentate mode or in monodentate and chelate modes, respectively, as o en found in other transition metal complexes with phenanthroline- and carboxylate-derived ligands (see, e.g.).46 The resulting coordination environment of the zinc(II) ions in 3 is a distorted tetrahedron while in 4, it is better described as a square pyramid

Results

Conclusion