title: Prediction of the aqueous solvation free energy of organic compounds by using autocorrelation of molecular electrostatic potential surface properties combined with response surface analysis.
abstract: Several quantitative structure-property relationship (QSPR) approaches have been explored for the prediction of aqueous solubility or aqueous solvation free energies, DeltaG(sol), as crucial parameter affecting the pharmacokinetic profile and toxicity of chemical compounds. It is mostly accepted that aqueous solvation free energies can be expressed quantitatively in terms of properties of the molecular surface electrostatic potentials of the solutes. In the present study we have introduced autocorrelation molecular electrostatic potential (autoMEP) vectors in combination with nonlinear response surface analysis (RSA) as alternative 3D-QSPR strategy to evaluate the aqueous solvation free energy of organic compounds. A robust QSPR model (r(cv)=0.93) has been obtained by using a collection of 248 organic chemicals. An external test set based on 23 molecules confirmed the good predictivity of the autoMEP/RSA model suggesting its further applicability in the in silico prediction of water solubility of large organic compound libraries.
authors.affiliation: Molecular Modeling Section (MMS), Dipartimento di Scienze Farmaceutiche, Università di Padova, via Marzolo 5, I-35131 Padova, Italy.
authors.forename: Lisa
authors.initials: L
authors.lastname: Michielan
authors.forename: Magdalena
authors.initials: M
authors.lastname: Bacilieri
authors.forename: Chosei
authors.initials: C
authors.lastname: Kaseda
authors.forename: Stefano
authors.initials: S
authors.lastname: Moro
mesh_terms: D003198:Computer Simulation; D009930:Organic Chemicals / Q000737:chemistry*; D011237:Predictive Value of Tests; D021281:Quantitative Structure-Activity Relationship; D015203:Reproducibility of Results; D054852:Small Molecule Libraries; D012995:Solubility; D055672:Static Electricity; D013499:Surface Properties; D013816:Thermodynamics; D014867:Water / Q000737:chemistry
chemical_list: D009930:Organic Chemicals; D054852:Small Molecule Libraries; D014867:Water