title: Individual Hydrogen-Bond Strength QSPR Modelling with ISIDA Local Descriptors: a Step Towards Polyfunctional Molecules.
abstract: Here, we introduce new ISIDA fragment descriptors able to describe "local" properties related to selected atoms or molecular fragments. These descriptors have been applied for QSPR modelling of the H-bond basicity scale pKBHX , measured by the 1 : 1 complexation constant of a series of organic acceptors (H-bond bases) with 4-fluorophenol as the reference H-bond donor in CCl4 at 298 K. Unlike previous QSPR studies of H-bond complexation, the models based on these new descriptors are able to predict the H-bond basicity of different acceptor centres on the same polyfunctional molecule. QSPR models were obtained using support vector machine and ensemble multiple linear regression methods on a set of 537 organic compounds including 5 bifunctional molecules. They were validated with cross-validation procedures and with two external test sets. The best model displays good predictive performance on a large test set of 451 mono- and bifunctional molecules: a root-mean squared error RMSE=0.26 and a determination coefficient R(2) =0.91. It is implemented on our website (http://infochim.u-strasbg.fr/webserv/VSEngine.html) together with the estimation of its applicability domain and an automatic detection of potential H-bond acceptors.
authors.affiliation: Laboratoire de Chémoinformatique, UMR 7140 CNRS, Université de Strasbourg, 1, rue Blaise Pascal, 67000 Strasbourg, France phone:+33368851560.
authors.forename: Fiorella
authors.initials: F
authors.lastname: Ruggiu
authors.affiliation: Institute of Physical Chemistry and Electrochemistry, Russian Academy of Sciences, Leninskiy prospect, 31a, 119991, Moscow, Russian Federation.
authors.forename: Vitaly
authors.initials: V
authors.lastname: Solov'ev
authors.affiliation: Laboratoire de Chémoinformatique, UMR 7140 CNRS, Université de Strasbourg, 1, rue Blaise Pascal, 67000 Strasbourg, France phone:+33368851560.
authors.forename: Gilles
authors.initials: G
authors.lastname: Marcou
authors.affiliation: Laboratoire de Chémoinformatique, UMR 7140 CNRS, Université de Strasbourg, 1, rue Blaise Pascal, 67000 Strasbourg, France phone:+33368851560.
authors.forename: Dragos
authors.initials: D
authors.lastname: Horvath
authors.affiliation: Université de Nantes, UMR CNRS 6230, Chimie Et Interdisciplinarité: Synthèse, Analyse, Modélisation (CEISAM), UFR Sciences & Techniques, 2, rue de la Houssinière, BP 92208, 44322 NANTES Cedex 3, France.
authors.forename: Jérôme
authors.initials: J
authors.lastname: Graton
authors.affiliation: Université de Nantes, UMR CNRS 6230, Chimie Et Interdisciplinarité: Synthèse, Analyse, Modélisation (CEISAM), UFR Sciences & Techniques, 2, rue de la Houssinière, BP 92208, 44322 NANTES Cedex 3, France.
authors.forename: Jean-Yves
authors.initials: JY
authors.lastname: Le Questel
authors.affiliation: Laboratoire de Chémoinformatique, UMR 7140 CNRS, Université de Strasbourg, 1, rue Blaise Pascal, 67000 Strasbourg, France phone:+33368851560. varnek@unistra.fr.
authors.forename: Alexandre
authors.initials: A
authors.lastname: Varnek
keywords: Equilibrium constants of hydrogen bonding; Fragment descriptors; H-bond; Hydrogen-bond acidity and basicity; ISIDA; QSPR; pKBHX