Assessing the Conformational Landscape of Dicarboxylic Acids Using Ab Initio Molecular Dynamics: The Role of Phase...

Molecules often adopt multiple conformations with distinct energies and reactivities, making it essential to characterize their conformational free energy landscape to understand their reactivity. Traditionally, computational studies identify stable molecular configurations using direct energy minimization with density functional theory (DFT), which effectively locates local minima. However, this approach does not fully capture the conformational landscape, particularly in the condensed phase where intermolecular interactions are playing a significant role. Here, we address this limitation by employing ab initio molecular dynamics (AIMD) to simulate the conformers of three dicarboxylic acids (DCAs), in both vapor and condensed phases. Our findings show that while direct energy minimization predicts the predominant conformer for fumaric acid (FA), AIMD is necessary to account for complex intermolecular interactions that stabilize additional conformers in succinic acid (SA) and maleic acid (MA). Specifically, AIMD reveals conformers that direct energy minimization does not predict to be thermally accessible but are stabilized by condensed-phase interactions. Additionally, we demonstrate a direct correlation between the density of the SA environment and the probability of forming external hydrogen bonds, which affects the conformational distribution. Finally, we demonstrate that these conformational distributions can serve as predictors for reactivity in an industrially relevant polyurethane acidolysis reaction.