Aqueous pK_a prediction for tautomerizable compounds using equilibrium bond lengths.

ABSTRACT: The accurate prediction of aqueous pK_a values for tautomerizable compounds is a formidable task, even for the most established in silico tools. Empirical approaches often fall short due to a lack of pre-existing knowledge of dominant tautomeric forms. In a rigorous first-principles approach, calculations for low-energy tautomers must be performed in protonated and deprotonated forms, often both in gas and solvent phases, thus representing a significant computational task. Here we report an alternative approach, predicting pK_a values for herbicide/therapeutic derivatives of 1,3-cyclohexanedione and 1,3-cyclopentanedione to within just 0.24 units. A model, using a single ab initio bond length from one protonation state, is as accurate as other more complex regression ap

SUBMITTER: Caine BA 

PROVIDER: S-EPMC9814527 | biostudies-literature | 2020 Feb

REPOSITORIES: biostudies-literature