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 | |
| State | Published - Oct 1 2015 |
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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
Cite this
Predicting hydration propensities of biologically relevant α-ketoamides. / Wedler, Henry B.; Palazzo, Teresa A.; Pemberton, Ryan P.; Hamann, Christian S.; Kurth, Mark J.; Tantillo, Dean J.
In: Bioorganic and Medicinal Chemistry Letters, Vol. 25, No. 19, 01.10.2015, p. 4153-4157.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Predicting hydration propensities of biologically relevant α-ketoamides
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
Y1 - 2015/10/1
N2 - 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.
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.
KW - Density functional theory
KW - Hydration propensity
KW - Predictive methods
KW - Theory versus experiment
KW - α-Ketoamide
UR - http://www.scopus.com/inward/record.url?scp=84945449221&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84945449221&partnerID=8YFLogxK
U2 - 10.1016/j.bmcl.2015.08.010
DO - 10.1016/j.bmcl.2015.08.010
M3 - Article
C2 - 26306983
AN - SCOPUS:84945449221
VL - 25
SP - 4153
EP - 4157
JO - Bioorganic and Medicinal Chemistry Letters
JF - Bioorganic and Medicinal Chemistry Letters
SN - 0960-894X
IS - 19
ER -