The AIBLHiCoS Method: Predicting Aqueous pKa Values from Gas-Phase Equilibrium Bond Lengths

Cate Anstöter; Beth A Caine; Paul L A Popelier

doi:10.1021/acs.jcim.5b00580

The AIBLHiCoS Method: Predicting Aqueous pKa Values from Gas-Phase Equilibrium Bond Lengths

Cate Anstöter, Beth A Caine, Paul L A Popelier

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

Abstract

The proposed AIBLHiCoS method predicts a given compound's pKa in aqueous solution from a single ab initio bond length only, after geometry optimization in the gas phase. Here we provide simple and predictive equations for naphthols and chemically similar biomolecules. Each linear equation corresponds to a High-Correlation Subset (HiCoS) that expresses the novel type of linear free energy relationship discovered here. The naphthol family exhibits a clear and strong relationship with the phenol family, with the "active" C-O bond always producing the highest correlations. The proposed method can isolate erroneous experiments and operate in non-aqueous solution and at different temperatures. Moreover, the existence of "active fragments" is demonstrated in a variety of sizable biomolecules for which the pKa is successfully predicted.

Original language	English
Pages (from-to)	471-83
Number of pages	13
Journal	Journal of Chemical Information and Modeling
Volume	56
Issue number	3
Early online date	15 Feb 2016
DOIs	https://doi.org/10.1021/acs.jcim.5b00580
Publication status	Published - 28 Mar 2016
Externally published	Yes

Keywords

Gases
Kinetics
Phenols/chemistry
Thermodynamics
Water/chemistry

Access to Document

10.1021/acs.jcim.5b00580

Cite this

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title = "The AIBLHiCoS Method: Predicting Aqueous pKa Values from Gas-Phase Equilibrium Bond Lengths",

abstract = "The proposed AIBLHiCoS method predicts a given compound's pKa in aqueous solution from a single ab initio bond length only, after geometry optimization in the gas phase. Here we provide simple and predictive equations for naphthols and chemically similar biomolecules. Each linear equation corresponds to a High-Correlation Subset (HiCoS) that expresses the novel type of linear free energy relationship discovered here. The naphthol family exhibits a clear and strong relationship with the phenol family, with the {"}active{"} C-O bond always producing the highest correlations. The proposed method can isolate erroneous experiments and operate in non-aqueous solution and at different temperatures. Moreover, the existence of {"}active fragments{"} is demonstrated in a variety of sizable biomolecules for which the pKa is successfully predicted. ",

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author = "Cate Anst{\"o}ter and Caine, {Beth A} and Popelier, {Paul L A}",

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T1 - The AIBLHiCoS Method

T2 - Predicting Aqueous pKa Values from Gas-Phase Equilibrium Bond Lengths

AU - Anstöter, Cate

AU - Caine, Beth A

AU - Popelier, Paul L A

PY - 2016/3/28

Y1 - 2016/3/28

N2 - The proposed AIBLHiCoS method predicts a given compound's pKa in aqueous solution from a single ab initio bond length only, after geometry optimization in the gas phase. Here we provide simple and predictive equations for naphthols and chemically similar biomolecules. Each linear equation corresponds to a High-Correlation Subset (HiCoS) that expresses the novel type of linear free energy relationship discovered here. The naphthol family exhibits a clear and strong relationship with the phenol family, with the "active" C-O bond always producing the highest correlations. The proposed method can isolate erroneous experiments and operate in non-aqueous solution and at different temperatures. Moreover, the existence of "active fragments" is demonstrated in a variety of sizable biomolecules for which the pKa is successfully predicted.

AB - The proposed AIBLHiCoS method predicts a given compound's pKa in aqueous solution from a single ab initio bond length only, after geometry optimization in the gas phase. Here we provide simple and predictive equations for naphthols and chemically similar biomolecules. Each linear equation corresponds to a High-Correlation Subset (HiCoS) that expresses the novel type of linear free energy relationship discovered here. The naphthol family exhibits a clear and strong relationship with the phenol family, with the "active" C-O bond always producing the highest correlations. The proposed method can isolate erroneous experiments and operate in non-aqueous solution and at different temperatures. Moreover, the existence of "active fragments" is demonstrated in a variety of sizable biomolecules for which the pKa is successfully predicted.

KW - Gases

KW - Kinetics

KW - Phenols/chemistry

KW - Thermodynamics

KW - Water/chemistry

U2 - 10.1021/acs.jcim.5b00580

DO - 10.1021/acs.jcim.5b00580

M3 - Article

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SN - 1549-9596

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SP - 471

EP - 483

JO - Journal of Chemical Information and Modeling

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