Novel copper(ii) complexes with fenamates and isonicotinamide: structure and properties, and interactions with DNA and serum albumin

Abstract

Reactions of non-steroidal anti-inflammatory drugs tolfenamic (Htolf), meclofenamic (Hmeclf), mefenamic (Hmef), clonixic (Hclon) and niflumic (Hnif) acids with isonicotinamide (isn) and copper(II) acetate resulted in the formation of five novel mixed-ligand Cu(II) coordination compounds: [Cu(tolf-O,O′)₂(isn-N)₂] (1), [Cu(meclf-O,O′)₂(isn-N)₂] (2), [Cu(mef-O,O′)₂(isn-N)₂] (3), [Cu(clon-O,O′)₂(isn-N)₂] (4), and [Cu(nif-O,O′)₂(isn-N)₂] (5). The structures of the complexes were determined by single-crystal X-ray analyses. The monomeric complexes build up 1D chains or 2D hydrogen bonding supramolecular networks. The intermolecular interactions were studied by Hirshfeld surface analysis. The redox properties of the complexes were studied by cyclic voltammetry. Cu redox cycling was documented by UV-vis and EPR spectroscopy. Formation of free radicals was monitored by the EPR trapping technique using a DMPO spin trap in a Fenton-like system. Evidence of reduction of the Cu(II) ions upon reaction with O₂˙⁻ was obtained using a specific chelator of Cu(I), neocuproine. The interaction of the complexes with bovine serum albumin was studied by fluorescence emission spectroscopy and the binding constants of the compounds to the albumin were calculated. The interaction of the complexes with calf-thymus DNA was monitored by diverse techniques (UV-vis spectroscopy, cyclic voltammetry, viscosity measurements) suggesting intercalation as the most possible mode of binding. DNA-competitive studies of the complexes with ethidium bromide were monitored by fluorescence emission spectroscopy.