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: Predicting hydration propensities of biologically relevant α-ketoamides. In: Bioorganic & Medicinal Chemistry Letters, 25 (19), pp. 4153-4157, 2015, ISSN: 0960-894X.

Abstract

Quantum chemical calculations coupled to experiments were used to predict covalent hydration propensities of biologically relevant $alpha$-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 $alpha$-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 $alpha$-ketoamides in biological environs.

BibTeX (Download)

@article{Wedler2015c,
title = {Predicting hydration propensities of biologically relevant α-ketoamides},
author = {Henry B Wedler and Teresa A Palazzo and Ryan P Pemberton and Christian S Hamann and Mark J Kurth and Dean J Tantillo},
url = {http://www.sciencedirect.com/science/article/pii/S0960894X15008343},
issn = {0960-894X},
year  = {2015},
date = {2015-10-01},
journal = {Bioorganic & Medicinal Chemistry Letters},
volume = {25},
number = {19},
pages = {4153-4157},
abstract = {Quantum chemical calculations coupled to experiments were used to predict covalent hydration propensities of biologically relevant $alpha$-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 $alpha$-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 $alpha$-ketoamides in biological environs.},
keywords = {Density functional theory, Hydration propensity, Predictive methods, Theory versus experiment, α-Ketoamide},
pubstate = {published},
tppubtype = {article}
}

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