ClogPalk: a method for predicting alkane/water partition coefficient

Abstract

Alkane/water partition coefficients (P(alk)) are less familiar to the molecular design community than their 1-octanol/water equivalents and access to both data and prediction tools is much more limited. A method for predicting alkane/water partition coefficient from molecular structure is introduced. The basis for the ClogP(alk) model is the strong (R² = 0.987) relationship between alkane/water partition coefficient and molecular surface area (MSA) that was observed for saturated hydrocarbons. The model treats a molecule as a perturbation of a saturated hydrocarbon molecule with the same MSA and uses increments defined for functional groups to quantify the extent to which logP(alk) is perturbed by the introduction each functional group. Interactions between functional groups, such as intramolecular hydrogen bonds are also parameterized within a perturbation framework. The functional groups and interactions between them are specified substructurally in a transparent and reproducible manner using SMARTS notation. The ClogP(alk) model was parameterized using data measured for structurally prototypical compounds that dominate the literature on alkane/water partition coefficients and then validated using an external test set of 100 alkane/water logP measurements, the majority of which were for drugs.

It Is Important to Compute Intramolecular Hydrogen Bonding in Drug Design?

“…Chen et al [354] estimated the H-bonding capability of an atom using the free energy required to transfer the atom from water to hexadecane. They then used a modification of the method of Kenny et al [355] to evaluate the Hbonding capability of the respective atoms in the proteinligand complex by calculating the difference (ΔlogP 16 ) between water/hexadecane partition coefficients (logP 16 ) and logP 16 of saturated hydrocarbon molecules with the same molecular surface area.…”

Technical Note: Development of chemoinformatic tools to enumerate functional groups in molecules for organic aerosol characterization

“…The concept of using SMILES and SMARTS patterns has been reported for applications in the atmospheric chemistry community (Barley et al, 2011;COBRA, Fooshee et al, 2012). While some sets of SMARTS patterns for substructure matching can additionally be found in the literature (Hann et al, 1999;Walters and Murcko, 2002;Olah et al, 2004;Enoch et al, 2008;Barley et al, 2011;Kenny et al, 2013) or on web databases -e.g., DAYLIGHT Chemical Information Systems, Inc. (DAYLIGHT Chemical Information Systems, Inc.) -knowledge regarding the extent of specificity and validation of the defined patterns is not available.…”

The Block Relevance (BR) analysis supports the dominating effect of solutes hydrogen bond acidity on ΔlogPoct–tol

“…The recent interest for the application of log P oct-alk in the drug discovery process stimulated the research for the design and implementation of tools for its prediction (Caron and Ermondi, 2005) (Toulmin et al, 2008) (Kenny et al, 2013).…”