Theoretical study on the ring-opening hydrolysis reaction of cAMP

Abstract The ring-opening hydrolysis reaction mechanism of cyclic 3′, 5′-adenosine monophosphate (cAMP) have been theoretically investigated at the B3LYP/6-31G** level. It is found that each ring-opening hydrolysis reaction of cAMP takes place via a four-membered transition state. For the reactions, H 2 O has two attacking sites (α and β). At each site, H 2 O has two attacking objects. One is the P atom, the other is the bond P–O, and they are competitive each other. The potential energy surface of reaction 4 is the lowest. The computations strongly support the experimental result that the nonenzymatic hydrolysis of cAMP yields 3′-AMP and in-line nonenzymatic hydrolysis of cAMP to 3′-AMP is the most advantageous hydrolysis reaction path. Our present calculations have rationalized and verified all the possible reaction channels.