Synthesis, characterization, crystal structure, DNA and human serum albumin interactions, as well as antiproliferative activity of a Cu(II) complex containing a Schiff base ligand formed in situ from the Cu(II)‐induced cyclization of 1,5‐bis(salicylidene)thiocarbohydrazide
Sidhali U. Parsekar, Paramita Haldar, P. K. Sudhadevi Antharjanam, Manjuri Kumar, Aditya P. Koley
Abstract
The reaction of Cu(OAc) 2 ·H 2 O with o ‐HOC 6 H 4 ‐C(H)N‐NH‐C(S)‐NH‐NC(H)‐C 6 H 4 OH‐ o in methanol resulted in the formation of a dinuclear Cu(II) complex [( o ‐phen)Cu(HL)Cu(HL)] ( 1 ) in the solution where HL 2− is a new O − NN − ligand formed in situ from cyclization of the Schiff base and the isolated product was found to be a dimer of 1 forming a tetranuclear compound in solid due to axial coordination of bridging phenolate O − as revealed from X‐ray crystallography. Electronic spectroscopic study using calf thymus DNA as well as fluorescence quenching study of ethidium bromide bound DNA in presence of 1 showed intercalative DNA binding with K b = 1.12 × 10 5 M −1 and K app = 8.80 × 10 5 M −1 , respectively. This compound was found to be efficient in hydrolytic as well as oxidative DNA cleavage. The binding interaction between complex 1 and human serum albumin (HSA) was investigated using fluorescence emission, absorption, and molecular docking studies. 3D fluorescence studies revealed that HSA structure was altered at secondary and tertiary levels. The binding constant K a value (~10 6 M −1 ) suggested a strong binding affinity of 1 to HSA, and the bimolecular quenching constant k q value (10 13 M −1 s −1 ) suggested a static quenching mechanism operative in the quenching of the intrinsic fluorescence of the protein. Such high k q value may also be accounted by Förster resonance energy transfer (FRET) process. The distance r (3.22 nm) between donor HSA and acceptor complex 1 calculated from FRET theory suggested that they are close to each other. 3‐(4,5‐Dimethylthiazol‐2‐yl)‐2,5‐diphenyltetrazolium bromide assay with human cervical cancer HeLa cells and human breast cancer MCF7 cells (IC 50 = 2.2 and 1.2 μM, respectively) suggested remarkable in vitro anticancer activity of 1 . Cell death in HeLa cells was induced via apoptosis as revealed from nuclear staining assays using Hoechst 33342 and acridine orange/propidium iodide dual staining, and apoptosis induction in HeLa cells happened through reactive oxygen species accumulation.