Cu(II) and Ni(II) Complexes with New Tridentate NNS Thiosemicarbazones: Synthesis, Characterisation, DNA Interaction, and Antibacterial Activity.

Dorian Polo-Cerón

doi:10.1155/2019/3520837

Abstract

This paper reports the synthesis and detailed characterisation of copper(II) and nickel(II) complexes with tridentate thiosemicarbazone ligands H 2 L1 and H 2 L2 derived from 2-acetylpyrazine. The ligands and their metal complexes were characterised by different physicochemical techniques, including elemental and thermogravimetric analysis; UV-Vis, IR, 1H-NMR, and 13C-NMR spectroscopy; molar conductance measurements; and mass spectrometry. The crystal structure of the H 2 L1 ligand was determined by single crystal X-ray diffraction studies. The spectral data showed that the thiosemicarbazone behaves as an NNS tridentate ligand through the nitrogen atoms of the azomethine group and pyrazine ring and the sulphur atom of the thioamide group. Elemental and thermal analyses indicated that the obtained metal complexes had a 1 : 1 stoichiometry (metal-ligand). The interactions between these complexes and calf thymus DNA (CT-DNA) were studied by electronic absorption and viscosity measurements. The activities of these compounds against oxidative DNA cleavage were examined by agarose gel electrophoresis. Cu(II) and Ni(II) complexes can wind DNA strands through groove interactions and promote strand breakage of the plasmid pmCherry under oxidative stress conditions. Moreover, all the complexes could interact more strongly with DNA than could with the free ligands. Finally, the antibacterial activities of the ligands and their complexes were determined by in vitro tests against Gram-positive bacterial strains (S. aureus ATCC 25923, L. monocytogenes ATCC 19115, and B. cereus ATCC 10876) and Gram-negative bacterial strains (E. coli ATCC 25922, S. typhimurium ATCC 14028, and K. pneumoniae ATCC BAA-2146) using the broth microdilution method. The metal complexes showed greater antimicrobial activities than the precursor ligands against some of the microorganisms.

Highlights

In recent decades, coordination compounds with transition metals have become quite important in medicinal chemistry [1,2,3,4]. e fight against infectious diseases, one aspect of this field, has seen great advances; antimicrobial resistance remains a major obstacle and continues to increase, and it is considered a global public health problem [5]
Considering the pharmacological potential of Cu(II) and Ni(II) thiosemicarbazone complexes and following our interest in developing new molecules with biological activity [2], this paper describes the synthesis and characterisation of Cu(II) and Ni(II) complexes with new N(4)-(4-R-phenyl) thiosemicarbazones derived from 2-acetylpyrazine. is study examines how these compounds interact with DNA strands through different experiments, in addition to testing their antibacterial activities against Gram-positive and Gram-negative bacterial strains
Synthesis and Characterisation of Ligands. e syntheses of 2-acetylpyrazine N(4)-phenylthiosemicarbazone (H2L1) and 2-acetylpyrazine N(4)-(4-chlorophenyl)thiosemicarbazone (H2L2) were performed through a three-step synthetic route (Scheme 1), following previously reported standard methodologies [14, 25, 26]

Summary

Introduction

Coordination compounds with transition metals have become quite important in medicinal chemistry [1,2,3,4]. e fight against infectious diseases, one aspect of this field, has seen great advances; antimicrobial resistance remains a major obstacle and continues to increase, and it is considered a global public health problem [5]. Multiple investigations have been performed to test new free organic or metal coordination compounds, which can be precursors of more efficient and less toxic drugs by acting through different biological mechanisms [6,7,8]. E electronic properties of the NNS donor system and the variety of chemical species that the system can produce are the reasons why TSC ligands act as good chelating agents that can coordinate with a great variety of transition metal ions, forming complexes that can change the biological activity of precursor ligands [12]. Bioinorganic Chemistry and Applications e interaction between these compounds and DNA has attracted great attention in medicinal chemistry due to the potential use of these complexes as antineoplastic agents [17]. Considering the pharmacological potential of Cu(II) and Ni(II) thiosemicarbazone complexes and following our interest in developing new molecules with biological activity [2], this paper describes the synthesis and characterisation of Cu(II) and Ni(II) complexes with new N(4)-(4-R-phenyl) thiosemicarbazones derived from 2-acetylpyrazine. is study examines how these compounds interact with DNA strands through different experiments, in addition to testing their antibacterial activities against Gram-positive and Gram-negative bacterial strains

Methods

Results

Conclusion