Mechanochemical synthesis of six Cu(II)complexes with selected thiols, their physicochemical characterization and interaction with DNA

Cysteine together with histidine (His2Cys)has been identified as one of the ligands in Type 1 copper protein active sites, and Cu-S(Cys)interaction determines their unique spectroscopic features. This work reports the synthesis of model Cu(II)-thiolates, which could mimic the Type 1 sites. The Cu (II)-complexes with l-cysteine, n-acetylcysteine, l-glutathione, l-penicillamine, mercaptosuccinic acid and dl-dithiothreitol were synthesized by solvent-free mechanochemical methods. The complexes were found to be of the ML2 type as revealed by solid-state analytical techniques including FT-IR (ATR)spectroscopy, Raman spectroscopy, electronic absorption spectroscopy (diffuse reflectance), powder X-ray diffraction and desorption electrospray ionization mass spectrometry. These compounds are difficult, in some cases impossible, to isolate from solution because of rapid oxidation of thiols to disulfides and reduction of Cu(II)to Cu(I)or Cu(0). However, in the solid state these complexes were found to be highly stable and exhibited spectroscopic features similar to those in the Type 1 site. Interaction of the complexes with genomic DNA isolated from human blood was studied by electrophoresis, which showed that Cu(II)-mercaptosuccinic acid and Cu(II)-n-acetylcysteine caused extensive degradation, whereas Cu(II)-penicillamine amd Cu(II)-glutathione significantly degraded the DNA. Cu(II)-cysteine appears to form DNA adducts. Docking of Cu(II)-cysteine with thioredoxine reductase suggests that the complex has the potential to inhibit the activity of the enzyme.