Abstract This study describes the design and implementation of a new chromatographic descriptor called log k′80 PLRP-S that provides information about the lipophilicity of drug molecules in the nonpolar environment, both in their neutral and ionized form. The log k′80 PLRP-S obtained on a polymeric column with acetonitrile/water mobile phase is shown to closely relate to log Ptoluene (toluene dielectric constant ε ∼ 2). The main intermolecular interactions governing log k′80 PLRP-S were deconvoluted using the Block Relevance (BR) analysis. The information provided by this descriptor was compared to ElogD and calclog Ptol, and the differences are highlighted. The "charge-flush" concept is introduced to describe the sensitivity of log k′80 PLRP-S to the ionization state of compounds in the pH range 2 to 12. The ability of log k′80 PLRP-S to indicate the propensity of neutral molecules and monoanions to form Intramolecular Hydrogen Bonds (IMHBs) is proven through a number of examples.

A Fast Chromatographic Method for Estimating Lipophilicity and Ionization in Nonpolar Membrane-Like Environment

CARON, Giulia
First
;
VALLARO, Maura;ERMONDI, Giuseppe;
2016-01-01

Abstract

Abstract This study describes the design and implementation of a new chromatographic descriptor called log k′80 PLRP-S that provides information about the lipophilicity of drug molecules in the nonpolar environment, both in their neutral and ionized form. The log k′80 PLRP-S obtained on a polymeric column with acetonitrile/water mobile phase is shown to closely relate to log Ptoluene (toluene dielectric constant ε ∼ 2). The main intermolecular interactions governing log k′80 PLRP-S were deconvoluted using the Block Relevance (BR) analysis. The information provided by this descriptor was compared to ElogD and calclog Ptol, and the differences are highlighted. The "charge-flush" concept is introduced to describe the sensitivity of log k′80 PLRP-S to the ionization state of compounds in the pH range 2 to 12. The ability of log k′80 PLRP-S to indicate the propensity of neutral molecules and monoanions to form Intramolecular Hydrogen Bonds (IMHBs) is proven through a number of examples.
2016
13
3
1100
1110
http://pubs.acs.org/journal/mpohbp
block relevance analysis; drug molecules; ElogD; intramolecular hydrogen bonds; ionization; lipophilicity descriptor; log Ptol; nonpolar environments; polymeric chromatographic column; 3003; Molecular Medicine; Drug Discovery3003 Pharmaceutical Science
Caron, Giulia; Vallaro, Maura; Ermondi, Giuseppe; Goetz, Gilles H.; Abramov, Yuriy A.; Philippe, Laurence; Shalaeva, Marina
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2318/1571833
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