Stability of formic acid/pyridine and isonicotinamide/formamide cocrystals by molecular dynamics simulations

A cocrystal is a system with at least two components that can be solids or liquids at room conditions. The molecules in a cocrystal interact by hydrogen bonds producing a new crystal that has different properties than the original compounds and also improved physicochemical properties. In this work, we study by molecular dynamics simulations the formic acid/pyridine and the isonicotinamide/formamide cocrystals at 173 and 150 K, respectively. Except isonicotinamide that is a solid, the rest of molecules are liquids at ambient conditions. The OPLS/AA force field is used with two sets of parameters for the liquids: (a) the original set obtained by matching the simulations results to experimental density and heat of vaporization at room conditions and (b) new values that reproduce the dielectric constant, surface tension and density at different temperatures. The parameters of pyridine and formamide have been published previously by our group (Salas et al. in J Chem Theory Comput 11(2):683, 2015). The liquid formic acid is parameterized in this work using the same procedure. The new parameters improved the predictions of the original values. The isonicotinamide parameters are obtained from those of pyridine and formamide assuming they are transferable. The structure and stability of cocrystals are determined through the calculation of distances and angles of atoms that form hydrogen bonds in different molecules. The simulation results are compared with experimental measurements of X-ray diffraction, and a good agreement is found. Although the new parameters for the liquids give simulation results of thermodynamic properties in better agreement with experimental data at different temperatures and pressures, the cocrystal results are essentially the same as those obtained using the original values.