Evidence for an Alternative Mechanism to a Previously Proposed Self-Replicating System

Article abstract of DOI:10.1021/jo00114a043

Rebek et al.^1,2 have proposed a "self-replicative" mechanism in which the amide product of an ester aminolysis forms a termolecular complex with the ester and amine reactants.In this manner, the product catalyzes its own formation.The evidence for the mechanism lies mainly in a 40-70percent acceleration when product is added externally to the reaction mixture.The system has now been reinvestigated owing, in part, to doubts created by troublesome experimental problems (e.g. small rate enhancements coupled to >/= 35percent unidentified side reactions) and by the entropic unlikehood of the highly constrained termolecular complex.Our new experiments prove that the Rebek mechanism is unnecessary.Thus, the aminolysis of simple naphthoyl and benzoyl esters, both lacking any hydrogen-bonding sites, are catalyzed by the Rebek "template".In the latter case, the reactions were run under the identical conditions used recently by Rebek (2 mM) while monitoring the formation of the major reaction product.Although the benzoyl ester cannot hydrogen-bond to the template, the ester aminolysis is catalyzed by the template to an extent even greater than that observed by Rebek (i.e. 2-fold).The Rebek mechanism, predicted upon ester/template binding, is clearly invalidated by these experiments.An alternative mechanism, involving amide catalysis, is proposed and found consistent with all available data.