Efficient Molecular Catalysis of ATP‐Hydrolysis by Protonated Macrocyclic Polyamines

Molecular catalysis of ATP‐hydrolysis by a number of protonated macrocyclic polyamines 1–9 has been investigated by ³¹P‐NMR spectroscopy, and marked rate enhancements have been obtained. The largest acceleration is produced by the [24]‐N₆O₂ macrocycle 1, and the process displays the following properties: 1. protonated 1 forms very stable complexes with ATP, as well as with ADP and AMP; 2. it enhances the rate of ATP‐hydrolysis by a factor of 10³ at pH = 8.5; the rate of hydrolysis is constant over a wide pH‐range, from pH = 2.5 to 8.5; 3. 1 is more efficient than acyclic analogues; 4. the products of the reaction are orthophosphate (OP) and ADP, which is subsequently hydrolyzed to OP and AMP at a slower rate; 5. at pH > 6.5, a transient species is detected, which is tentatively identified as a phosphoramidate intermediate, resulting from phosphorylation of the macrocycle 1; 6. the reaction presents first‐order kinetics and is catalytic. The mechanism of the process is discussed in terms of initial formation of a complex between ATP and protonated 1, followed by an intracomplex reaction which may involve a combination of nucleophilic or acid catalysis with electrostatic catalysis. Copyright © 1983 Verlag GmbH & Co. KGaA, Weinheim