A comparative study of the antioxidant properties of chalcone derivatives through the Fe chelation mechanism

Abstract

This dissertation reports the results of a theoretical investigation on the conformational and antioxidant properties of four chalcone derivatives, namely butein, homobutein, kanakugiol and pedicellin, through their Fe coordination ability. Chalcone derivatives have been reported to possess various biological activities such as anticancer, antimalarial and antioxidant. The antioxidant activities of chalcone derivatives have been investigated extensively from an experimental approach and from a theoretical approach using the hydrogen atom and electron transfer mechanism. However, there is scarce information on the metal chelation ability of these compounds as pertaining to their antioxidant properties; therefore, the study reported here investigated the Fen+ chelation ability of four chalcone derivatives. The selection of the Feⁿ⁺ cations is based on the fact that they have been utilised extensively in the experimental investigation of antioxidant activity of biologically active molecules. The conformers of the isolated chalcone derivatives were investigated with the aim of understanding factors influencing their stability and as starting point for obtaining the lowest-energy conformer(s) that can be utilised in the study involving the Feⁿ⁺ cations. The ligand---Feⁿ⁺ complexes were investigated with the objective of elucidating the nature of the complexes, Fe---ligand stabilities, metal ion affinities and electronic properties of the cations before and after complexation. The study was performed in vacuo and in water solution by utilising the DFT/B3LYP and DFT/BP86 methods. The 6-31+G(d,p) basis set was utilised to describe the C, H, O atoms and the LANL2DZ basis set was selected to describe the Fen+ cations. Final energies were obtained by running single point calculations on the optimised geometries using the 6-311+G(2d,p) basis set. The results suggest that conformational stability of the selected chalcone derivatives is influenced by the presence of intramolecular hydrogen bonds, arrangement of the 2-propen-1-one aliphatic chain and in the cases of homobutein, kanakugiol and pedicellin, the orientation of the methoxy groups. The stability of the ligand---Feⁿ⁺ complexes is influenced by the media (the relative energy values in water are dampened relative to those obtained in vacuo), the nature of the Fen+ cation and the nature of the ligand---Feⁿ⁺ interactions; the binding energies depend on the media (they are higher in vacuo than in water solution), the site for coordination of the Feⁿ⁺ cation as well as the nature of the cation. The reducing ability of the chalcone derivatives were assessed by the reduction of charge on the Feⁿ⁺ cation after complexation. All the selected chalcone derivatives exhibited the ability to reduce the Feⁿ⁺ cation, which indicates that all the investigated chalcone derivatives may play an important role as antioxidant molecules.