EVIDENCE FOR AN ALTERNATIVE MECHANISM TO A PREVIOUSLY PROPOSED SELF-REPLICATING SYSTEM

Rebek et al.(1,2) have proposed a ''self-replicative'' mechanism in wh ich the amide product of an ester aminolysis forms a termolecular comp lex with the ester and amine reactants. In this manner, the product ca talyzes its own formation. The evidence for the mechanism lies mainly in a 40-70% acceleration when product is added externally to the react ion mixture. The system has now been reinvestigated owing, in part, to doubts created by troublesome experimental problems (e.g. small rate enhancements coupled to greater than or equal to 35% unidentified side reactions) and by the entropic unlikelihood of the highly constrained termolecular complex. Our new experiments prove that the Rebek mechan ism is unnecessary. Thus, the aminolysis of simple naphthoyl and benzo yl esters, both lacking any hydrogen-bonding sites, are catalyzed by t he Rebek ''template''. In the latter case, the reactions were run unde r the identical conditions used recently by Rebek (2 mM) while monitor ing the formation of the major reaction product. Although the benzoyl ester cannot hydrogen-bond to the template, the ester aminolysis is ca talyzed by the template to an extent even greater than that observed b y Rebek (i.e. 2-fold). The Rebek mechanism, predicated upon ester/temp late binding, is clearly invalidated by these experiments. An alternat ive mechanism, involving amide catalysis, is proposed and found consis tent with all available data.