Synthesis, characterization, cellular uptake and interaction with native DNA of a bis(pyridyl)-1,2,4-oxadiazole copper(ii) complex

Abstract

The copper(II) complex of 3,5-bis(2′-pyridyl)-1,2,4-oxadiazole was synthesized and characterized. X-Ray crystallography revealed that the complex consists of a discrete [Cu(3,5-bis(2′-pyridyl)-1,2,4-oxadiazole)₂(H₂O)₂]²⁺ cation and two ClO₄⁻ anions. The Cu^II coordination sphere has a distorted octahedral geometry and each ligand chelates the copper ion through the N(4) nitrogen of the oxadiazole ring and the nitrogen of one pyridine moiety. The coordinated water molecules are in cis position and each of them is H-bonded to the 5-pyridyl nitrogen of the oxadiazole ligand and to an oxygen of the perchlorate anion. Biological assays showed that, despite the free ligand not being effective, [Cu(3,5-bis(2′-pyridyl)-1,2,4-oxadiazole)₂(H₂O)₂]²⁺ reduced the vitality of human hepatoblastoma HepG2 and colorectal carcinoma HT29 cells in a dose- and time-dependent manner. The interaction of the cationic copper complex with native DNA was investigated by variable-temperature UV-vis spectroscopy, circular dichroism, viscosity and gel electrophoresis, indicating that it is a groove binder with binding constant K_b = 2.2 × 10⁴ M⁻¹.