Theoretical Exploration of Enhanced Antioxidant Activity in Copper Complexes of Tetrahydroxystilbenes: Insights into Mechanisms and Molecular Interactions

Abstract

A theoretical investigation was conducted using DFT/PW91/TZP/DMSO calculations on a complete set of exhaustive lists of 18 compounds resulting from the complexation of trans-2,4,3',5'-tetrahydroxystilbene (T-OXY) and cis-2,4,1',3'-tetrahydroxystilbene (C-OXY) with copper metal cations (Cu⁺ and Cu²⁺). The ligand-binding sites are the critical points of Quantum Theory of Atoms in Molecules (QTAIM) analysis on neutral and deprotonated ligands. Various mechanisms, including hydrogen atom transfer (HAT), sequential proton loss electron transfer (SPLET), single electron transfer followed by proton transfer (SET-PT), and bond dissociation energy (BDE(E0)) calculations, were employed to quantify the antioxidant activity. The BDE(E0) mechanism emerged as the most suitable approach for such analyses to evaluate the departure of hydrogen atoms since the results show the HAT mechanism is the most likely occurring. Particularly intriguing were the anionic Cu⁺ complexes with ligands adopting trans configurations and deprotonated conformations, displaying superior antioxidant activity compared to their counterparts. Remarkably, a single ligand within the Cu⁺ complex exhibited exceptional antioxidant prowess, yielding a BDE(E0) value of 91.47 kcal/mol. Furthermore, a complex involving two deprotonated ligands demonstrated antioxidant activity of 31.12 kcal/mol, signifying its potential as a potent antiradical agent, surpassing T-OXY by a factor of 3.91 and even surpassing the antioxidant efficiency of Vitamin C.

Figure 1

Graphic representation of bond critical points (BCPs in red) and ring critical points (RCPs in green) of T-OXY and C-OXY with QTAIM analysis by PW91/TZP in DMSO.

Figure 2

Optimized structures using computational level DFT/PW91/TZP/DMSO of Cu⁺ complexes with mono-2,4,3′,5′-tetrahydroxystilbene neutral and deprotonated at the binding sites.

Figure 3

Optimized structures using computational level DFT/PW91/TZP/DMSO of Cu²⁺ complexes with mono-2,4,3′,5′-tetrahydroxystilbene neutral and deprotonated at the binding sites.

Figure 4

Chemical structures of cis- and trans-OXY.

Figure 5

Optimized structures of Cu⁺ and Cu²⁺ complexes with bi-2,4,3′,5′-tetrahydroxystilbene neutral and deprotonated by PW91/TZP in DMSO.

Figure 6

Graphical representation of HOMOs and LUMOs of Cu⁺ and Cu²⁺ complexes, respectively, by the PW91/TZP/DMSO level of theory.

Figure 7

Graphic representation of various energy contributions of Cu⁺ complexes.

Figure 8

Graphic representation of various energy contributions of Cu²⁺ complexes.

Figure 9

Graphic representation of various energy contributions of Cu⁺ and Cu²⁺ complexes.