A Tetranuclear copper(II) Complex with a Pyridine‐2,6‐dicarboxamide Ligand: Structural and Magnetic Properties and In vitro Antiproliferative Activity Against Human Cancer Cells

Abstract A pentadentate diamide ligand, N,N′‐di(pyridine‐2‐yl)pyridine‐2,6‐dicarboxamide (L 1 H 2 ) and its tetranuclear Cu(II) complex [Cu 4 (L 1 ) 2 (μ 3 ‐OH) 2 (H 2 O) 3 (ClO 4 )](ClO 4 ) ⋅ H 2 O are reported. X‐ray crystal structure of the complex reveals that it has an open‐book type architecture. Two central copper atoms are connected to each other by two hydroxo bridges. Each of these two hydroxo bridges also connects the two central copper atoms to one of the two terminal copper atoms. Variable temperature susceptibility measurements show that χ M T decreases with the temperature, indicating a strong antiferromagnetic behavior. With the help of DFT calculations the magnetic data was analyzed using the spin Hamiltonian H =−2 J 1 S 3 ⋅ S 4 −2 J 2 (S 3 ⋅ S 1 + S 3 ⋅ S 2 + S 4 ⋅ S 1 + S 4 ⋅ S 2 )−2 J 3 S 1 ⋅ S 2 (where subscripts 1 and 2 refer to the terminal copper atoms and 3 and 4 refer to the central copper atoms). The best fit was obtained with 2 J 1 =−322 cm −1 , 2 J 2 =+34.8 cm −1 , 2 J 3 =−8.8 cm −1 and g =2.18, indicating a δ‐type interaction between terminal copper atoms. The complex proves to be an avid binder of ct‐DNA, with apparent binding constant (K app ) value estimated as 1.536×10 7 M −1 . In vitro experiments indicate that the Cu(II) complex reduced the proliferation of HCT116 cells among other cell lines. This reduction of cell proliferation may be attributed to the enhancement of intracellular ROS, along with modulation and disruption of cell cycle associated proteins. SKC conceptualized the project, arranged funding and involved in overall coordination among collaborators, analyzing the data, and writing the paper. AM was involved in doing the experimental work on synthesis of the compounds, carrying out analytical and spectroscopic measurements, collecting X‐ray crystallographic data and DNA binding experiments. MS , SM and KDS were involved in study of anticancer activities of the complex. SS helped in refining X‐ray structure of the complex. MC did the magnetic measurements and analysis whereas AF did the DFT calculations.