????The a-ketoamide functionality is common in many pharmaceuticals on the market today and is found as a moiety of numerous natural products that are attracting significant interest. However, no literature exists on hydration equilibrium constants of a-ketoamides, which dictate whether the ketoamide will be in the keto or geminal diol form in various conditions. Physiological conditions are of particular interest to us, as these conditions resemble the environment that a-ketoamide functionalities would be in in ingested pharmaceuticals.Hydration propensities of biologically-relevant a-ketoamides were determined using water as an implicit solvent using computational chemistry. By computing hydration equilibria of many ketones and aldehydes with known hydration equilibrium constants and developing a good correlation between our calculated equilibrium constants and experimental constants, we constructed a method that anyone can use to determine accurate hydration equilibria for a-ketoamides and similar carbonyl compounds computationally. We have not located any experimental hydration equilibrium constants for a-ketoamides that we can use to validate our method, so we have executed a one-step, one-pot synthesis of several aryl a-ketoamides. We will determine experimental hydration equilibria by performing population analysis of the keto and geminal diol forms using proton NMR. We will then compare these newly-determined experimental equilibria to our computational results to obtain a correlation which will validate our computational method.

Theoretical hydration energies of biologically relevant a-ketoamides

247th National Meeting (2014)

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