Quantum mechanical study of interaction between phenolic compounds as inhibitor with active site of human carbonic anhydrase enzyme

CO2, bicarbonate and protons are an essential molecule and ions for many important physiologic processes occurring in all living organisms. However, the uncatalyzed rate ofinterconversion of such species is too slow to meet the physiological needs of most biochemical processes. This task is efficiently accomplished by the carbonic anhydrases. This superfamily of metals-enzymes possess within their active sites a highly nucleophilic metal hydroxide species, such as zinc(II), cadmium(II) or iron (II) hydroxide, depending on the class [1]. Phenol and its derivatives were reported to be a competitive inhibitor of human Carbonic Anhydrase II (hCA II). The phenolic moiety has an amphiphilic character. The presence of the hydrophobic planar aromatic ring is responsible for hydrophobic interactions (π-stacking), whereas at the same time the polar hydroxyl groups can participate in hydrogen bonding. This dual behavior allows these molecules to bind to the amino acid residues of several proteins, enzymes or receptors Figure 1 [2]. In the present research the mechanism of the inhibition of phenolic compounds with active form of CA (II) using DFT calculations have been investigated. The electronic structure and electronic energy of all studied compounds have been calculated in the gas phase and then in water solvent using B3LYP and split-valance6-31G* basis set.