Understanding @entity11064 and @entity9734 transfer is central to many biochemical processes. However, despite decades of experimental and computational studies, a consensus concerning the precise mechanistic details of these reactions has yet to be reached. In this work we perform a detailed comparative theoretical study of the hydrolysis of @entity7480 , @entity68488 and @entity68489 , all of which have served as key model systems for understanding @entity11064 and @entity9734 transfer reactions, respectively. We demonstrate the existence of energetically similar but mechanistically distinct possibilities for @entity42839 hydrolysis. The calculated kinetic isotope effects for @entity7480 provide a means to discriminate between substrate- and solvent-assisted pathways of @entity1391 monoester hydrolysis, and show that the solvent-assisted pathway dominates in solution. This preferred mechanism for @entity7480 hydrolysis is difficult to find computationally due to the limitations of compressing multiple bonding changes onto a 2-dimensional energy surface. This problem is compounded by the need to include implicit solvation to at least microsolvate the system and stabilize the highly charged species. In contrast, @entity68488 hydrolysis shows a preference for a substrate-assisted mechanism. For @entity68489 hydrolysis there is only one viable reaction pathway, which is similar to the solvent-assisted pathway for @entity1391 hydrolysis, and the substrate-assisted pathway is not accessible. Overall, our results provide a unifying mechanistic framework that is consistent with the experimentally measured kinetic isotope effects and reconciles the discrepancies between theoretical and experimental models for these biochemically ubiquitous classes of reaction.

Resolving Apparent Conflicts between Theoretical and Experimental Models of XXXX Monoester Hydrolysis.

@entity68489 :: ('MESH:C023379', 'Chemical') :: ['p-nitrophenyl sulfate'] @entity42839 :: ('CHEBI:7794', 'Chemical') :: ['phosphate monoester'] @entity1391 :: ('CHEBI:26020', 'Chemical') :: ['phosphate'] @entity9734 :: ('CHEBI:29825', 'Chemical') :: ['sulfuryl'] @entity68488 :: ('MESH:C027265', 'Chemical') :: ['methyl phosphate'] @entity11064 :: ('CHEBI:29315', 'Chemical') :: ['phosphoryl'] @entity7480 :: ('MESH:C008644', 'Chemical') :: ['p-nitrophenyl phosphate']
@entity1391 :: (CHEBI:26020,Chemical) :: ['Phosphate']
