Dissociation of a tripodal pyridyl-pyrazole ligand and assortment of metal complex: Synthesis, structure, DFT, thermal stability, cytotoxicity, DNA cleavage, and molecular docking studies

A tripodal pyridyl-pyrazole based N,N,O donor ligand ( L ) has been designed, and it's copper(II) complex, [Cu(L1)Cl-2](2).(dmpzH)2 ( 1 ) where dmpzH refers protonated dimethylpyrazole, and manganese(II) complex, [Mn(L)(Cl)(2)] ( 2 )] have been synthesized and characterized by a combination of various spectroscopy, Xray crystallography, electrochemical, thermogravimetric and density functional theory. The X-ray structure of 1 showed the copper(II) coordinated by the two sets of NO donors which had been assorted from the ligand ( L ) along with two bridging and one terminal chloride atoms. The distorted square-planar centrosymmetric structure of 1 is further stabilized by the hydrogen bonding with exogenous protonated pyrazole units that had been extracted from L . The title ligand retained its original structure when bound with Mn(II) giving a pseudo-octahedral geometry. The central Mn(II) was coordinated by two pyrazolyl nitrogen (N1, N7), one tertiary amine nitrogen (N3), one carbohydrazide oxygen atom O1, and two exogenous chloride ions in a cis disposition. Cytotoxicity experiments carried out in a series of human cell lines (IMR-32, HepG2 and HeLa) to confirm the apoptotic mechanism of cell death, predominantly in IMR-32. The DNA cleavage studies were then performed in the presence of the synthesized compounds to verify the influence of ligand structural features in their nuclease activity. Complex 2 was able to cause double-strand DNA scissions both in an oxidizing and reducing environment, whereas complex 1 broke the single-strand DNA in a reducing environment only, suggesting its potential anticancer therapeutics. To shed a better understanding of DNA-substrate interaction, a molecular docking study was performed.(C) 2022 Elsevier B.V. All rights reserved.

Automated summary

This study designed and synthesized a tripodal pyridyl-pyrazole based N,N,O donor ligand and its copper and manganese complexes. The synthesized compounds were characterized using various spectroscopy, X-ray crystallography, electrochemical, thermogravimetric, and density functional theory techniques. The cytotoxicity experiments confirmed the potential apoptotic mechanism of cell death, while the DNA cleavage studies verified the nuclease activity of the compounds. Furthermore, a molecular docking study was performed to investigate the interaction between the compounds and DNA substrate.