Efficient Molecular Catalysis of ATP‐Hydrolysis by Protonated Macrocyclic Polyamines

Abstract

Abstract Molecular catalysis of ATP‐hydrolysis by a number of protonated macrocyclic polyamines 1–9 has been investigated by 31 P‐NMR spectroscopy, and marked rate enhancements have been obtained. The largest acceleration is produced by the [24]‐N 6 O 2 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 10 3 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.