Cu (II) and Co (II/III) complexes of N,O-chelated Schiff base ligands: DNA interaction, protein binding, cytotoxicity, cell death mechanism and reactive oxygen species generation studies

A series of copper (II) (1and3) and cobalt (II/III) (2,4and5) complexes comprising different imino-phenolate ligandsDCH,DTHandDBH(2)(whereDCH= 2,4-dichloro-6-((mesitylimino)methyl)phenol,DTH= 2,4-di-tert-butyl-6-((mesitylimino)methyl) phenol andDBH(2)= 2,4-dibromo-6-((mesitylimino)methyl)phenol) have been prepared with excellent yield and high purity. By utilizing different spectroscopic tools such as UV-visible, electrospray ionization (ESI)-mass, Fourier-transform infrared (FTIR) spectrometry and elemental analysis, the prepared complexes (1-5) were thoroughly characterized. The molecular structure of the synthesized complexes was ascertained by using single-crystal X-ray diffraction studies (SCXRDs). The experiment reveals that Complexes1-5bind to calf thymus DNA (CT-DNA) through non-intercalative way with good interacting abilities. However,1-5are excellent quenchers of the fluorescence intensity of bovine serum albumin (BSA) following the static pathway. Additionally, they had shown remarkable cytotoxic potential against MCF-7 (mammary gland adenocarcinoma) and A549 (lung adenocarcinoma) cell lines. The IC(50)values associated with these complexes were much lower than the conventional drug cisplatin. Apoptosis-induced cell death was confirmed from the DNA fragmentation studies and Hoechst 33342 staining. The 2 ',7 '-dichlorofluorescein diacetate (DCFDA) assay indicates that the complex mediated reactive oxygen species (ROS) generation is accountable for governing the apoptosis mechanism via oxidative cell distress. Apart from these studies, by carrying out density functional theory (DFT) method, highest occupied molecular orbital-lowest unoccupied molecular orbital (HOMO-LUMO) energy gap calculations and optimized structures of the synthesized complexes were accomplished.

Automated summary

A series of copper and cobalt complexes with different imino-phenolate ligands were synthesized and their interaction with DNA, albumin, and cancer cells were studied, showing significant cytotoxic potential and involvement in inducing apoptosis mechanism.