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dc.contributor.authorPalmer, David S.
dc.contributor.authorMcDonagh, James L.
dc.contributor.authorMitchell, John B. O.
dc.contributor.authorvan Mourik, Tanja
dc.contributor.authorFedorov, Maxim V.
dc.identifier.citationPalmer , D S , McDonagh , J L , Mitchell , J B O , van Mourik , T & Fedorov , M V 2012 , ' First-principles calculation of the intrinsic aqueous solubility of crystalline druglike molecules ' , Journal of Chemical Theory and Computation , vol. 8 , no. 9 , pp. 3322-3337 .
dc.identifier.otherPURE: 39211173
dc.identifier.otherPURE UUID: e0ec1e1c-b1cb-4ef0-8702-72da865ac80b
dc.identifier.otherWOS: 000308830700035
dc.identifier.otherScopus: 84962388394
dc.identifier.otherORCID: /0000-0002-0379-6097/work/34033399
dc.identifier.otherORCID: /0000-0001-7683-3293/work/57088449
dc.description.abstractWe demonstrate that the intrinsic aqueous solubility of crystalline druglike molecules can be estimated with reasonable accuracy from sublimation free energies calculated using crystal lattice simulations and hydration free energies calculated using the 3D Reference Interaction Site Model (3D-RISM) of the Integral Equation Theory of Molecular Liquids (IET). The solubilities of 25 crystalline druglike molecules taken from different chemical classes are predicted by the model with a correlation coefficient of R = 0.85 and a root mean square error (RMSE) equal to 1.45 log(10) S units, which is significantly more accurate than results obtained using implicit continuum solvent models. The method is not directly parametrized against experimental solubility data, and it offers a full computational characterization of the thermodynamics of transfer of the drug molecule from crystal phase to gas phase to dilute aqueous solution.
dc.relation.ispartofJournal of Chemical Theory and Computationen
dc.rightsCopyright © 2012 American Chemical Society. This work has been made available online in accordance with publisher policies or with permission. Permission for further reuse of this content should be sought from the publisher or the rights holder. This is the author created accepted manuscript following peer review and may differ slightly from the final published version. The final published version of this work is available at
dc.subjectQD Chemistryen
dc.titleFirst-principles calculation of the intrinsic aqueous solubility of crystalline druglike moleculesen
dc.typeJournal articleen
dc.contributor.institutionUniversity of St Andrews. School of Chemistryen
dc.contributor.institutionUniversity of St Andrews. Biomedical Sciences Research Complexen
dc.contributor.institutionUniversity of St Andrews. EaSTCHEMen
dc.description.statusPeer revieweden

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