Predicting when precipitation-driven synthesis is feasible: Application tobiocatalysis

Precipitation-driven synthesis offers the possibility of obtaining high rea ction yields using very low volume reactors and is finding increasing appli cations in biocatalysis. Here, a model that allows straightforward predicti on of when such a precipitation-driven reaction will be thermodynamically f easible is presented. This requires comparison of the equilibrium constant, K-eq,with the saturated mass action ratio, Z(sat), defined as the ratio of product solubilities to reactant solubilities. A hypothetical thermodynami c cycle that can be used to accurately predict Z(sat) in water is described . The cycle involves three main processes: fusion of a solid to a supercool ed liquid, ideal mixing of the liquid with octanol, and partitioning from o ctanol to water. To obtain the saturated mass action ratio using this cycle , only the melting points of the reactants and products, and in certain cas es the pK(a) of ionisable groups, are required as input parameters. The mod el was tested on a range of enzyme-catalysed peptide syntheses from the lit erature and found to predict accurately when precipitation-driver reaction was possible. The methodology employed is quite general and the model is th erefore expected to be applicable to a wide range of other (bio)-catalysed reactions.