Details zur Publikation

Kategorie Textpublikation
Referenztyp Zeitschriften
DOI 10.1021/ci200233s
Titel (primär) Prediction of the dissociation constant pKa of organic acids from local molecular parameters of their electronic ground state
Autor Yu, H.; Kühne, R. ORCID logo ; Ebert, R.-U.; Schüürmann, G.
Quelle Journal of Chemical Information and Modeling
Erscheinungsjahr 2011
Department OEC
Band/Volume 51
Heft 9
Seite von 2336
Seite bis 2344
Sprache englisch
Abstract

A quantum chemical method has been developed to estimate the dissociation constant pKa of organic acids from their neutral molecular structures by employing electronic structure properties. The data set covers 219 phenols (including 29 phenols with intramolecular H-bonding), 150 aromatic carboxylic acids, 190 aliphatic carboxylic acids, and 138 alcohols, with pKa varying by 16 units (0.38–16.80). Optimized ground-state geometries employing the semiempirical AM1 Hamiltonian have been used to quantify the site-specific molecular readiness to donate or accept electron charge in terms of both charge-associated energies and energy-associated charges, augmented by an ortho substitution indicator for aromatic compounds. The resultant regression models yield squared correlation coefficients (r2) from 0.82 to 0.90 and root-mean-square errors (rms) from 0.39 to 0.70 pKa units, corresponding to an overall (subset-weighted) r2 of 0.86. Simulated external validation, leave-10%-out cross-validation and target value scrambling demonstrate the statistical robustness and prediction power of the derived model suite. The low intercorrelation with prediction errors from the commercial ACD package provides opportunity for a consensus model approach, offering a pragmatic way for further increasing the confidence in prediction significantly. Interestingly, inclusion of calculated free energies of aqueous solvation does not improve the prediction performance, probably because of the limited precision provided by available continuum-solvation models.
dauerhafte UFZ-Verlinkung https://www.ufz.de/index.php?en=20939&ufzPublicationIdentifier=11620
Yu, H., Kühne, R., Ebert, R.-U., Schüürmann, G. (2011):
Prediction of the dissociation constant pKa of organic acids from local molecular parameters of their electronic ground state
J. Chem Inf. Model. 51 (9), 2336 - 2344 10.1021/ci200233s