The Block Relevance (BR) analysis to aid medicinal chemists to determine and interpret lipophilicity

Abstract

A major issue related to chromatographic determination of lipophilicity is about the conversion to log P. 5The interconversion of lipophilicity indexes can be made only if two systems express the same balance of intermolecular solute/system forces. The deconvolution of intermolecular interactions is generally obtained by solvation parameter models. Block Relevance (BR) analysis is a new tool specifically designed for medicinal chemists to interpret partitioning/retention phenomena in a very practical way. This paper describes the application of BR analysis to literature data (ElogP) and experimentally 10 determined chromatographic indexes on a Supelcosil TM LC-ABZ column for a series of 36 drugs. Results indicate that BR analysis is a solid and reliable tool that captures the main information encoded in any lipophilicity descriptor.

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

“…Figure 2B indicates that the larger the molecule, the higher its partitioning in the octanol phase and thus the higher its log P oct . The whole profile of intermolecular interactions is in line with BR plots obtained on different datasets (Caron and Ermondi, 2013).…”

“…BR analysis was performed as described elsewhere (Ermondi and Caron, 2012) (Caron and Ermondi, 2013).…”

“…S2) are often hard to be interpreted. To overcome this problem we extended the VIPs analysis with the BR analysis, a recent methodology introduced in (Ermondi and Caron, 2012) (Caron and Ermondi, 2013). BR analysis mandates the organization of the VS+ descriptors into six blocks (namely, Size, Water, DRY, N1, O and Others, definitions and more details in Table 2) which enables a straightforward understanding of the investigated phenomena (e.g., partitioning in the considered biphasic system).…”

“…BR analysis is a new tool that enables the mechanistic interpretation of PLS models (Ermondi and Caron, 2012) (Caron and Ermondi, 2013). Also, we report about a BR analysis based comparison of log P oct-tol and log P oct-alk .…”

Investigating the Influence of (Deoxy)fluorination on the Lipophilicity of Non‐UV‐Active Fluorinated Alkanols and Carbohydrates by a New log P Determination Method

“…HPLC-based methods [14] are less suitable when accurate log P values are required and subject to limitations. [15] Above all, quantification typically rests on UV spectroscopy,w hich hampers the measurement of non-UVactive solutes (even commercially). NMR-based methods [12a, 16] are cumbersome or not easily amenable for use in typical multiuser NMR facilities.T he calculation of log P is also possible (clog P), but accuracyi ss trongly dependent on the training sets used, stereochemistry cannot be taken into account, and errors of multiple log P units are no exception.…”