title: The Block Relevance (BR) analysis supports the dominating effect of solutes hydrogen bond acidity on ΔlogP(oct-tol).
abstract: The role of hydrogen bond acidity, i.e., the ability of chemicals to act as hydrogen bond donors (HBD), is a crucial element in pharmaceutical sciences and medicinal chemistry. It has been shown that the difference between logP values (ΔlogP) obtained in two different biphasic systems is informative of the solutes HBD properties and thus useful in the prediction of drugs human fate. In this study, we collected from literature more than 200 experimental logPtol (the logarithm of the partition coefficient P in the toluene/water system) values along with their corresponding logPoct (the logarithm of the partition coefficient P in the octanol/water system) values. The dataset was processed using a purposely-built in-house software to remove molecules that are potentially able to form IMHBs. On the remaining structures the ΔlogPoct-tol (=logPoct - logPtol) have been calculated and correlated with 82 VolSurf+descriptors through a PLS model. Finally the Block Relevance (BR) analysis has been used to group the descriptors in six easy-to-interpret blocks and to show graphically the relevance of a certain block in the PLS model. BR analysis showed that the hydrogen bond donor (HBD) properties of the solutes mainly govern ΔlogPoct-tol. This supports the use of ΔlogPoct-tol to estimate HBD properties of solutes and its role in the intramolecular hydrogen bonding (IMHB) interpretation scheme recently reported in the literature.
authors.affiliation: Molecular Biotechnology and Health Sciences Dept., Università degli Studi di Torino, via Quarello 15, 10135 Torino, Italy.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Ermondi
authors.affiliation: Computer Science Dept., Università degli Studi di Torino, Corso Svizzera 185, 10149 Torino, Italy.
authors.forename: Alessia
authors.initials: A
authors.lastname: Visconti
authors.affiliation: Computer Science Dept., Università degli Studi di Torino, Corso Svizzera 185, 10149 Torino, Italy.
authors.forename: Roberto
authors.initials: R
authors.lastname: Esposito
authors.affiliation: Molecular Biotechnology and Health Sciences Dept., Università degli Studi di Torino, via Quarello 15, 10135 Torino, Italy. Electronic address: giulia.caron@unito.it.
authors.forename: Giulia
authors.initials: G
authors.lastname: Caron
mesh_terms: D020003:1-Octanol / Q000737:chemistry*; D055808:Drug Discovery / Q000379:methods*; D006860:Hydrogen Bonding; D006863:Hydrogen-Ion Concentration; D016018:Least-Squares Analysis; D004364:Pharmaceutical Preparations / Q000737:chemistry; D014050:Toluene / Q000737:chemistry*; D014867:Water / Q000737:chemistry
chemical_list: D004364:Pharmaceutical Preparations; D014867:Water; D014050:Toluene; D020003:1-Octanol
keywords: BR analysis; Hydrogen bond acidity; Lipophilicity; VolSurf+; ΔLogP