Interactive Copigmentation in Multicopigment Systems: Mechanistic Insights from Thermodynamics and Molecular...

Copigmentation enhances and stabilizes wine anthocyanin color, but its behavior in multicopigment systems remains unclear. In this study, we investigated the interaction between malvidin-3-O-glucoside and gallic acid, caffeic acid, catechin, and quercetin-3-O-glucoside, focusing on additive and inhibitory effects. Multiple copigments increased the calculated fraction of red flavylium cation by up to 75%, indicating additive effects, whereas binary copigmentation showed -14.13% to -78.7% lower hyperchromic effects relative to the corresponding single-copigment. Thermodynamic analysis showed contrasting enthalpy-entropy compensation patterns depending on whether a stronger copigment was introduced into a weaker system or vice versa. Quantum-chemical calculations supported possible ternary complexes and provided plausible structural explanations for inhibition. Molecular dynamics simulations further suggested competing association processes and direct copigment-copigment interactions. Collectively, these results support that natural copigmentation is a dynamic multicomponent equilibrium governed by competitive and cooperative interactions, providing a framework for understanding nonlinear color responses in complex wine matrices.