Thioether sulfur-bound [Cu2] complexes showing catechol oxidase activity and DNA cleaving behaviour

Abstract

Rational ligand design approaches allowed {Cu₂(μ-OH/OMe)} cores to be accommodated within μ-phenoxido bis(tetradentate) and μ-phenoxido bis(tridentate) ligands having thioether donors. The complexes [Cu₂(μ-H₂L1)(μ-OH)](ClO₄)₂·2H₂O (1), [Cu₂(μ-L2)(μ-OH)(OH₂)](ClO₄)₂ (2a) and [Cu₂(μ-L2)(μ-OCH₃)(OH₂)](ClO₄)₂ (2b) were obtained from an N₂O₃S₂ donor set bearing the H₃L1 ligand (2,6-bis-[{2-(2-hydroxyethylthio)ethylimino}methyl]-4-methylphenol) and N₂OS₂ donor set containing the HL2 ligand (4-methyl-2,6-bis-[{2-(methylthio)phenylimino}methyl]phenol) without showing double phenoxido bridging or any type of preformed inter-fragment aggregation. Previously, we showed that H₃L (2,6-bis[((2-(2-hydroxyethoxy)ethyl)imino)methyl]-4-methylphenol), the ether analogue of H₃L1, in the presence of carboxylate anions, was responsible for the self-aggregation of preformed {Cu₂} fragments and gave two types of [Cu₄] complexes comprising [Cu₄O] and [Cu₄(OH)₂] cores (T. S. Mahapatra, A. Bauzá, D. Dutta, S. Mishra, A. Frontera and D. Ray, ChemistrySelect, 2016, 1, 64–74). The molecular structures of 1, 2a and 2b were determined via single crystal X-ray diffraction and solution studies, which indicated the presence of [Cu₂] species. This was further confirmed via UV-vis spectroscopy and HRMS analysis. The synthesized complexes were screened for their potential as catalysts for the catalytic oxidation of 3,5-di-tert-butylcatechol (3,5-DTBCH₂). A change in the mechanism of catalytic oxidation was observed with a change in the ligand backbone. All three complexes also showed DNA binding properties, which were further substantiated via molecular docking studies. Their DNA binding affinities were quantitatively ascertained using their intrinsic binding constant, K_b, values which were found to be 4.2 × 10⁴, 5.6 × 10⁴ and 4.8 × 10⁴ M⁻¹, respectively. Furthermore, the complexes displayed efficient DNA cleavage behaviour with pBR322 and the oxidative path was established in presence of ROS, singlet oxygen, ¹O₂, and the superoxide anion, O₂·⁻.