Structural Characterisation and Docking Studies of Copper Homocysteine Complex with Cytochrome c Oxidase, Glutathione Peroxidase, Superoxide Dismutase for Evaluation of Metal Mediated Homocysteine Toxicity

Abstract

An emerging understanding of the role and regulation of homocysteine metal ion interactions during oxidative injury which leads to vascular pathogenesis underlines metal ion importance and need for more research on this aspect. In the present work metal ion interactions in solution and as well as solid state were carried out. Synthesized Cu (II), Ni (II) and Zn (II) complexes with homocysteine. The complexes were further characterized spectrally with IR, UV, Mass, ESR, X-ray photoelectron spectroscopy and TGA techniques. The possible geometries of metal complexes were evaluated using the molecular mechanics calculations. The refined structures were screened based on lowest strain energies calculated by applying MM3 force field. The molecular docking study of copper complex was performed by using Autodock4.2 software against Cytochrome C oxidase, Glutathione peroxidase 1 and Superoxide Dismutase 1 enzymes. Based on analytical, conductance, magnetic and electronic spectral data the Cu (II) and Zn (II) complexes are assigned tetrahedral geometry and Ni (II) complex is assigned square planar geometry. These complexes are formulated as [M(L)H2O]. The formation constants for the interaction of metal ions with homocysteine under physiological conditions as well as the structure and composition of metal complexes synthesized provide some evidence to earlier biochemical studies on animal models. The docking values obtained in the present study may provide supporting information for the biochemical studies related to homocysteine toxicity in presence of metal ions. The binding interactions at these enzymes active site revealed that copper homocysteine complex interaction led to Inhibition of COX, SOD and Glutathione peroxidase enzymes activity, a possible mechanism for therapeutic intervention to treat diseases caused by homocysteine toxicity