title: Predicting hydration propensities of biologically relevant α-ketoamides.
abstract: Quantum chemical calculations coupled to experiments were used to predict covalent hydration propensities of biologically relevant α-ketoamides. Experimentally determined hydration equilibrium constants for related ketones and aldehydes were compared to computationally determined values to develop a method for predicting hydration equilibrium constants. This method was used on six newly synthesized α-ketoamides to experimentally verify computational predictions. A correlation between calculation and experiment was observed and applied to models of several pertinent APIs. Our results indicate that the keto form is favored for practically all α-ketoamides in biological environs.
authors: Department of Chemistry, University of California, Davis, 1 Shields Avenue, Davis, CA 95616, USA.
authors: Henry B
authors: HB
authors: Wedler
authors: Department of Chemistry, University of California, Davis, 1 Shields Avenue, Davis, CA 95616, USA.
authors: Teresa A
authors: TA
authors: Palazzo
authors: Department of Chemistry, University of California, Davis, 1 Shields Avenue, Davis, CA 95616, USA.
authors: Ryan P
authors: RP
authors: Pemberton
authors: Department of Chemistry & Biochemistry, Albright College, Reading, PA 19604, USA.
authors: Christian S
authors: CS
authors: Hamann
authors: Department of Chemistry, University of California, Davis, 1 Shields Avenue, Davis, CA 95616, USA.
authors: Mark J
authors: MJ
authors: Kurth
authors: Department of Chemistry, University of California, Davis, 1 Shields Avenue, Davis, CA 95616, USA.
authors: Dean J
authors: DJ
authors: Tantillo
mesh_terms: D000577:Amides / Q000737:chemistry*; D008958:Models, Molecular; D015394:Molecular Structure; D011789:Quantum Theory; D014867:Water / Q000737:chemistry*
chemical_list: D000577:Amides; D014867:Water
keywords: Density functional theory; Hydration propensity; Predictive methods; Theory versus experiment; α-Ketoamide