Investigation of protein/DNA binding, and cytotoxicity of novel Cu() and Zn()-dipyrazinyl pyridine complexes

Two new transition metal complexes of a dipyrazinylpyridine (dppy) ligand 3,4-diethoxyphenyl-2,6-di(pyrazine-2-yl)pyridine L , {[CuL 2 ]Cl 2 ( 1 ) and [ZnL 2 ]Cl 2 ( 2 )}, have been synthesized and characterized using NMR (for L and 2 ), UV-vis spectroscopy, ESR (for 1 ), HRMS, elemental analysis and DFT study. Upon interaction with bovine serum albumin (BSA), complexes 1 and 2 demonstrated varying binding capabilities, with 1 displaying superior binding (binding constant 4.5 × 10 4 M −1 ) towards BSA than 2 (binding constant 1.2 × 10 4 M −1 ). Similarly, with calf-thymus DNA (ct-DNA), 1 showed better binding affinity (1.1 × 10 6 M −1 ) than 2 (8.5 × 10 5 M −1 ) as observed from UV-visible spectroscopy. The mechanism that leads to the quenching of BSA fluorescence by 1 and 2 is attributed to static quenching. The complexes demonstrated an intercalative binding mode with ct-DNA, and molecular docking has been employed to elucidate the biomolecular interactions with the complexes. Circular dichroism spectra have been utilized to confirm the binding and assessment of the interactions with the biomolecules. Furthermore, studies of the anticancer potentials of 1-2 were evaluated using the Dalton's lymphoma (DL) cancer cell line. Following 48 hours of treatment, the IC 50 values for 1 and 2 were identified as 24 μM and 28 μM, respectively, indicating their potency in inhibiting cancer cell growth. Novel Cu( ii ) and Zn( ii ) complexes of a dipyrazinyl pyridine (dppy) ligand L , {[CuL 2 ]Cl 2 ( 1 ) and [ZnL 2 ]Cl 2 ( 2 )}, have been prepared and their binding affinity with protein/DNA and in vitro cytotoxicity have been studied.