Synthesis and crystal structure determination of a mononuclear cobalt(ii) complex derived from 4-(pyridin-4-ylmethoxy)-benzoic acid: evaluation of the DNA/protein interaction and photo-induced pBR322 DNA cleavage

Abstract

New metal-based chemotherapeutic drug candidate [Co(L)₂·(H₂O)₄] (1) was synthesized from ligand 4-(pyridin-4-ylmethoxy)-benzoic acid (HL) and thoroughly characterized by spectroscopic, analytical and single crystal X-ray diffraction techniques. The crystal structure analysis reveal that the asymmetric unit of the complex consists of one Co(II) ion, one L⁻ ligand and two coordinated aqua molecules. The Co(II) ion is coordinated to four oxygen atoms from four aqua molecules. Hence, the geometry around the Co(II) ion can be described as a MN₂O₄ octahedral geometry. In vitro DNA binding studies of complex 1 with CT DNA were carried out by employing various biophysical techniques viz. electronic absorption, fluorescence and circular dichroism techniques to examine the binding propensity of 1 towards CT DNA. The experimental results revealed that complex 1 avidly binds to CT DNA via an electrostatic mode and the intrinsic binding constant K_b value was found to be 4.25 × 10⁴ M⁻¹. Complex 1 shows significant DNA photo cleavage activity through the formation of hydroxyl radicals via a photo-redox pathway. Futhermore, interaction studies of complex 1 with human serum albumin (HSA) revealed the quenching of intrinsic fluorescence of the HSA Trp 214 residue through a static quenching mechanism.