Phase equilibria play a central role in most chemical processes ranging from fractional distillation of organic mixtures, extraction with selective solvents, to crystallization of specfic forms of drug molecules. In fact, such separation processes are often dominating productions costs for many chemicals and pharmaceuticals. The prediction of phase equilibria of multicomponent mixtures is one of the grand challenges for molecular simulation requiring both accurate force fields and efficient sampling algorithms. The ternary liquid-liquid-vapor phase diagram below was predicted from a simulation of a three-component mixture that may find potential use for biphasic catalytic systems. At elevated pressures, carbon dioxide swells the two liquid phases and these expanded phases become more miscible. Above the upper critical solution pressure, the catalytic reaction can progress rapidly in the single liquid phase. Thereafter, the pressure is lowered and phase separation occurs. Thus, the separation of the fluorous catalyst (soluble in the fluorocarbon phase) from the organic products (soluble in the hydrocarbon phase) is greatly facilitated.
In the area of phase equilibria, the Siepmann group's research interests are directed toward tunable solvents, adsorbed films, and polymorphism and solvate formation of pharmaceutical solids. There is great need to develop environmentally benign and highly tunable process solvents that can replace chlorinated or fluorinated solvents. Molecularly-thin fluid films adsorbed on solid substrates play a central role for lubrication and as protective surface coating. Polymorphism, the ability of a given molecule to crystalize into different solid forms or to form crystalline solvates upon addition of stochiometric amounts of solvent, is an important problem for the pharmaceutical and food industries because certain polymorphs have desirable properties (e.g., stability, bioavailability, or dissolution characteristics) and individual polymorphic forms may be patentable. One of the continuing scandals of science, as emphasized by John Maddox (former editor of Nature), is that there is no general method for the predicition of crystal structures from molecular formulae, and that designing organic solids with specific and desired properities remains only a dream [G.R. Desiraju, Nature Materials 1, 77-79 (2002)].