Efficient Molecular Catalysis of ATP-Hydrolysis by Protonated Macrocyclic Polyamines

Article abstract of DOI:10.1002/hlca.19830660811

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 ortho phosphate (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.