For reversible reactions that do not occur in aqueous buffers, the pre-equilibrated DCC approach can be used. The DCL was initially generated (or pre-equilibrated) in organic solvent, and then diluted into aqueous buffer containing the protein target for selection. Organic based reversible reactions, including Diels-Alder[38] and alkene cross metathesis reactions,[39] have been proposed or applied to protein-directed DCC using this method.