Density functional investigations on alkali metal (Li, Na, K) catalyzed thymidylyl (3′-5′) thymidine phosphodiester hydrolysis

► Reaction pathways of alkali metal catalyzed Tp-OT hydrolysis are analyzed. ► Transition states on either side of intermediate points to (AN + DN) mechanism. ► Activation free energy data in water reveal a trend: Li < Na < K. ► MED topography used to quantify bond formation/cleavage during hydrolysis.