Maura Vallaro

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

A major issue related to chromatographic determination of lipophilicity is the conversion to logP. The interconversion of lipophilicity indices 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 determined chromatographic indices on a Supelcosil™ 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.

Learning how to use IAM chromatography for predicting permeability

Abstract The interest for IAM (Immobilized Artificial Membranes) chromatography in the prediction of drug permeability is increasing. Here we firstly set‐up a dataset of 253 molecules including neutral and ionized drugs and few organic compounds for which we either measured or retrieved from the literature IAM.PC.DD2 log KwIAM data. Then we applied block relevance (BR) analysis to extract from PLS models the relative contribution of intermolecular forces governing log KwIAM and &Dgr;log KwIAM (a combined descriptor calculated from log KwIAM). Finally, the relationship between log KwIAM, &Dgr;log KwIAM and passive permeability determined in both PAMPA and MDCK‐LE systems was looked for. Models provided the basis for a rational application of IAM chromatography in permeability prediction. Graphical abstract Figure. No caption available.

Blended-learning for courses in Pharmaceutical Analysis. Part 2

Based on previous experience with the blended-learning for courses in Pharmaceutical Analysis we designed and implemented a new course institutionally organized in two semesters with the dual purpose of using blended learning as a tool to achieve the full integration of the two modules and to enable an efficient learning of the practical aspects of the course.

Log P as a tool in intramolecular hydrogen bond considerations

Intramolecular hydrogen bonding (IMHB) considerations are gaining relevance in drug discovery and a molecular descriptor which can predict very early the capacity of a compound to form IMHB is needed to speed up the optimization process of drug candidates. Although log Poct is largely used for optimization purposes, in this paper we firstly use the Block Relevance (BR) analysis to theoretically show how log Poct is not a convenient choice to assess IMHB properties of candidates. Then we discuss the limits of log Poct and introduce Δlog Poct-tol, i.e. the difference between log Poct and log Ptol (the logarithm of the partition coefficient in the toluene/water system). Finally, we provided some examples also including bRo5 protease inhibitors, to clarify how to interpret Δlog Poct-tol values.