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

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

Chemistry

Research output: Contribution to journal › Article › peer-review

1 Scopus citations

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.

Original language	English (US)
Pages (from-to)	4153-4157
Number of pages	5
Journal	Bioorganic and Medicinal Chemistry Letters
Volume	25
Issue number	19
DOIs	https://doi.org/10.1016/j.bmcl.2015.08.010
State	Published - Oct 1 2015

Keywords

Density functional theory
Hydration propensity
Predictive methods
Theory versus experiment
α-Ketoamide

ASJC Scopus subject areas

Biochemistry
Clinical Biochemistry
Molecular Biology
Molecular Medicine
Organic Chemistry
Drug Discovery
Pharmaceutical Science

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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.",

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AU - Wedler, Henry B.

AU - Palazzo, Teresa A.

AU - Pemberton, Ryan P.

AU - Hamann, Christian S.

AU - Kurth, Mark J.

AU - Tantillo, Dean J.

PY - 2015/10/1

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AB - 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.

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KW - Theory versus experiment

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