A Fast Chromatographic Method for Estimating Lipophilicity and Ionization in Nonpolar Membrane-Like Environment.
Mol Pharm
; 13(3): 1100-10, 2016 Mar 07.
Article
en En
| MEDLINE
| ID: mdl-26767433
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 ⼠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.
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Banco de datos:
MEDLINE
Asunto principal:
Acetonitrilos
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Polímeros
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Tolueno
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Preparaciones Farmacéuticas
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Agua
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Cromatografía Líquida de Alta Presión
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Membranas
Idioma:
En
Año:
2016
Tipo del documento:
Article