Structure-making solvation of ferulic acid across protic and aprotic solvents: viscosity experiments, simulations, and implications for antioxidant function

Abstract

Solvent structure-making is an important feature of molecular organization in liquids as it shapes thermodynamic, dynamic and reactive properties. In this paper, we combine experimental and computational approaches to elucidate the structure-making behaviour of trans-4-hydroxy-3-methoxycinnamic acid (ferulic acid, FA) in a series of solvents: the protic alcohols methanol, ethanol, and 2-propanol, and the aprotic solvents tetrahydrofuran (THF) and dimethyl sulfoxide (DMSO). Precise viscometric measurements over 11 temperatures in the molality range from ∼0.01 to ∼0.5 mol kg⁻¹ reveal that FA acts as a structure-maker across all solutions. Molecular dynamics simulations complement these findings, revealing marked cross-species correlations and mixed clusters in protic solvents. Hydrogen-bond analysis highlights the long lifetimes of cross-species hydrogen bonds, underscoring the dual donor–acceptor capacity of FA. The insights from experiments and simulations provide a molecular foundation for understanding how solute-induced structure-making by ferulic acid influences solvent organization, and ultimately, properties such as viscosity and antioxidant performance.