On the role of isomeric composition in determining the stability of liquid phases: A Molecular Dynamics study of acetaldehyde phenylhydrazone

Acetaldehyde phenylhydrazone (APH) exists as a pair of E and Z isomers, but only the Z form is known to form crystals. Crystalline Z-APH was the subject of intense research efforts for over a century due to an erratic melting behavior, which failed to find satisfactory explanations. The mystery was solved just a few years ago, when Threlfall showed that melting involves partial isomerization, which might be sped up even by trace of acid catalysts. In this work, we apply the Molecular Dynamics tools available in the Milano Chemistry Molecular Simulation (MiCMoS) package, to explain the compositional stability range of the liquid, as estimated by NMR measurements. We also propose a cheap protocol to predict relevant thermodynamic state functions, based on experimental estimates for the equilibrium composition. We show that electrostatic interactions favor partially ordered arrangements of close neighboring molecules, which assume elongated antiparallel conformations. This interaction geometry is not easily achieved by Z isomers, which are constrained to bear partially folded hydrocarbon chains, and form liquids with lower cohesive energy. The consequence is that E-diluted solutions are enthalpically unfavored. Increasing the concentration of E reduces the enthalpic penalty and provides a favorable entropy of mixing, until partial molecular ordering at short range makes the entropic term unfavorable as well. The equilibrium is achieved when the entropic term is still large and positive enough to contrast the enthalpic cost. We predict that this occurs within the ≤ x(E) ≤ 0.6 compositional range, in good agreement with the experimental estimate. The applicability of our method to the general case of binary mixtures of organic liquids is discussed in the context of providing a molecular-level understanding of the observed thermodynamic properties.