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

Abstract

A series of copper (II) (1 and 3) and cobalt (II/III) (2, 4 and 5) complexes comprising different imino-phenolate ligands DCH, DTH and DBH 2 (where DCH = 2,4-dichloro-6-((mesitylimino)methyl)phenol, DTH = 2,4-di-tert-butyl-6-((mesitylimino)methyl) phenol and DBH 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 Complexes 1-5 bind to calf thymus DNA (CT-DNA) through non-intercalative way with good interacting abilities. However, 1-5 are 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 0 ,7 0-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.

Reactions of cobalt(ii) chloride and cobalt(ii) acetate with hemisalen-type ligands: ligand transformation, oxidation of cobalt and complex formation. Preliminary study on the cytotoxicity of Co(ii) and Co(iii) hemisalen complexes

“…Though not emphasized, the change of the cobalt oxidation state was observed previously for the reactions of other diphenol imines with Co( ii ) salts. 16,19 Therefore, we suggest that diphenolate ligands strongly stabilize the +3 oxidation number of cobalt.…”

“…[12][13][14][15][16][17] Schiff bases feature exciting properties related to the simultaneous presence of proton-donor and proton-acceptor groups, the possibility of formation of inter-and intramolecular hydrogen bonds and participation in proton transfer processes. [16][17][18][19][20][21][22][23][24] Based on these properties, imines are widely used in organic processes, such as the addition of organometallic reagents to C]N bond, 16,20,21,25,26 hydrolysis to aldehyde/ketone and amine, 21,27,28 self-condensation, 25,[29][30][31][32] complexation reactions with both main groups and transition metals, 21,33,34 pHand metal ion-dependent hydrolysis on the metal center during the formation of the coordination complex. [35][36][37][38] In our previous work, we described the immediate hydrolysis of the imine HL1 (2-methoxy-6-(E-2-pyridyliminomethyl)phenol) in the presence of nickel cations.…”

Transition Metal Complexes with Tridentate Schiff Bases (O N O and O N N) Derived from Salicylaldehyde: An Analysis of Their Potential Anticancer Activity

“…The authors hypothesized that the higher DNA‐binding affinity and higher K b value are possible reasons for the increased cytotoxic activity of Co‐02 . Additional experiments confirm that Co‐02 binds to DNA (calf thymus) in a non‐intercalated manner, that it is an excellent inhibitor of BSA fluorescence intensity via the static pathway, and that it induces cell death by apoptosis by generating ROS through cellular oxidative stress [117] …”

Synthesis, structural elucidation, biological screening, and density functional theory calculations of Cu(II), Ni(II), Mn(II), and Co(II) complexes of 20 Z‐N‐((Z)‐2‐(6‐nitrobenzo[d]thiazol‐2‐ylimino)‐1,2‐diphenylethylidene)‐5‐nitrobenzo[d]thiazol‐2‐amine Schiff base ligand

“…Schiff base‐derived metal complexes are well renowned to exhibit their binding ability towards drug proteins with the serum albumins. [ 22,23 ] The abundance of serum albumins proteins in the blood is employed in the drug transportation of drug molecules in the body human. These bindings of metal‐derived drugs have a significant impact on the distribution of drugs and their metabolism in the human body.…”