Supramolecular catalysis in the hydrolysis of ATP facilitated by macrocyclic polyamines: mechanistic studies

Article abstract of DOI:10.1021/ja00236a036

Protonated polyaza macrocycles that bind anionic substrates can perform reactions on the bound species and provide information on the various factors contributing to catalysis.They form stable complexes wtih adenosine triphosphate, adenosine diphosphate, and pyrophosphate, and these supramolecular assemblies catalyze the solvolysis of the bound substrates. 31P NMR was found to be a useful technique both for the kinetic analysis and for the detection of unstable intermediates formed in the reaction.The 24-membered macrocyclic polyamine, 1,4,7,13,16,19-hexaaza-10,22-dioxocyclotetradecane (<24>N6O2,1), catalyzed the hydrolysis of ATP at both pH 3 and 7 with calculated entropies of activation of -11 and -8.7 eu.The reaction is intensive to ionic strength; however, both sodium and chloride ions depress the k_obsd at pH 7.The reaction at neutral pH is characterized by nucleophilic catalysis with the formation of the symmetrical monophosphorylated derivative 2 of macrocycle 1; a Δs of -26 eu was found for the solvolysis of 2 at pH 7.A series of related 22- to 32-membered rings containing up to 10 groups demonstrated specific structural requiments for effective cataysis of the hydrolytic reactions.Analogues of 1 wherein the oxygen atoms are either replaced by amino groups (<24>N₈,4) or removed (<22>N2C4, 6) enhanced the rate of ATP hydrolysis at pH 3 by a factor of 300.Clear evidence for electrostatic and nucleophilic catalysis coupled with potential sites for acid and base catalysis make such macrocycles fruitful materials for the study of the mechanisms of molecular catalysis in polyphosphate hydrolysis, as well as models for the processes that may occur in enzymes utilizing ATP and related species as substrates or phosphoryl donors.