Weak intermolecular forces lie at the heart of biochemical recognition phenomenon and the last decade has seen much activity in the evaluation of these forces. A number of model systems have been developed including macrocyclic structures and molecular clefts. With these structures it has been possible to measure forces at the sub-kilocalorie level involving hydrogen bonding, aromatic stacking and van der Waals interactions. This manuscript deals with molecular clefts as synthetic receptors for nucleic acid components and their ultimate use in developing chemical reactions between components within a complex. This has led to an entirely synthetic, self-replicating system that shows the features of self-complementarity and autocatalysis. A general discussion of self-replicating systems and their implications for prebiotic chemistry is developed.