Predicting hydration propensities of biologically relevant α-ketoamides

Henry B Wedler; Teresa A Palazzo; Ryan P Pemberton; Christian S Hamann; Mark J Kurth; Dean J Tantillo

doi:10.1016/j.bmcl.2015.08.010

Predicting hydration propensities of biologically relevant α-ketoamides

Bioorg Med Chem Lett. 2015 Oct 1;25(19):4153-7. doi: 10.1016/j.bmcl.2015.08.010. Epub 2015 Aug 12.

Authors

Henry B Wedler¹, Teresa A Palazzo¹, Ryan P Pemberton¹, Christian S Hamann², Mark J Kurth¹, Dean J Tantillo¹

Affiliations

¹ Department of Chemistry, University of California, Davis, 1 Shields Avenue, Davis, CA 95616, USA.
² Department of Chemistry & Biochemistry, Albright College, Reading, PA 19604, USA.

PMID: 26306983
DOI: 10.1016/j.bmcl.2015.08.010

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.

Keywords: Density functional theory; Hydration propensity; Predictive methods; Theory versus experiment; α-Ketoamide.

MeSH terms

Amides / chemistry*
Models, Molecular
Molecular Structure
Quantum Theory
Water / chemistry*

Substances

Amides
Water