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

Molecular Pharmaceutics
Giulia CaronMarina Shalaeva

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.

References

Nov 25, 2003·Journal of Chromatography. B, Analytical Technologies in the Biomedical and Life Sciences·Salwa K Poole, Colin F Poole
Feb 19, 2004·Journal of Chromatography. a·Rebeca RuizElisabeth Bosch
Feb 24, 2010·Journal of Medicinal Chemistry·Bernd KuhnMartin Stahl
Nov 29, 2011·European Journal of Pharmaceutical Sciences : Official Journal of the European Federation for Pharmaceutical Sciences·Károly Mazák, Béla Noszál
Mar 1, 2010·Expert Opinion on Drug Discovery·Michael J Waring
May 7, 2013·Journal of Chemical Information and Modeling·Senthil NatesanStefan Balaz
May 29, 2013·Journal of Medicinal Chemistry·Marina ShalaevaMichael J Shapiro
Dec 21, 2013·European Journal of Pharmaceutical Sciences : Official Journal of the European Federation for Pharmaceutical Sciences·Giuseppe ErmondiGiulia Caron
Mar 20, 2014·Journal of Medicinal Chemistry·Gilles H GoetzMichael J Shapiro
Oct 15, 2014·ACS Medicinal Chemistry Letters·Gilles H GoetzMichael J Shapiro
Apr 25, 2015·International Journal of Pharmaceutics·Giulia CaronGiuseppe Ermondi

❮ Previous
Next ❯

Citations

May 18, 2016·International Journal of Pharmaceutics·Giuseppe Ermondi, Giulia Caron
Oct 16, 2016·Future Medicinal Chemistry·Giulia Caron, Giuseppe Ermondi
Dec 14, 2016·Future Medicinal Chemistry·Giulia Caron, Giuseppe Ermondi
Dec 31, 2016·Molecular Pharmaceutics·Gilles H GoetzLaurence Philippe
Jan 20, 2019·Medicinal Research Reviews·Giulia CaronGiuseppe Ermondi
Feb 24, 2020·European Journal of Pharmaceutical Sciences : Official Journal of the European Federation for Pharmaceutical Sciences·Giuseppe ErmondiGiulia Caron
Mar 16, 2021·European Journal of Pharmaceutical Sciences : Official Journal of the European Federation for Pharmaceutical Sciences·Giuseppe ErmondiGiulia Caron
Jul 16, 2021·ACS Medicinal Chemistry Letters·Giuseppe ErmondiGiulia Caron
Apr 24, 2020·Journal of Medicinal Chemistry·Christopher P Tinworth, Robert J Young

❮ Previous
Next ❯

Related Concepts

Trending Feeds

COVID-19

Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Blastomycosis

Blastomycosis fungal infections spread through inhaling Blastomyces dermatitidis spores. Discover the latest research on blastomycosis fungal infections here.

Nuclear Pore Complex in ALS/FTD

Alterations in nucleocytoplasmic transport, controlled by the nuclear pore complex, may be involved in the pathomechanism underlying multiple neurodegenerative diseases including Amyotrophic Lateral Sclerosis and Frontotemporal Dementia. Here is the latest research on the nuclear pore complex in ALS and FTD.

Applications of Molecular Barcoding

The concept of molecular barcoding is that each original DNA or RNA molecule is attached to a unique sequence barcode. Sequence reads having different barcodes represent different original molecules, while sequence reads having the same barcode are results of PCR duplication from one original molecule. Discover the latest research on molecular barcoding here.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Evolution of Pluripotency

Pluripotency refers to the ability of a cell to develop into three primary germ cell layers of the embryo. This feed focuses on the mechanisms that underlie the evolution of pluripotency. Here is the latest research.

Position Effect Variegation

Position Effect Variagation occurs when a gene is inactivated due to its positioning near heterochromatic regions within a chromosome. Discover the latest research on Position Effect Variagation here.

STING Receptor Agonists

Stimulator of IFN genes (STING) are a group of transmembrane proteins that are involved in the induction of type I interferon that is important in the innate immune response. The stimulation of STING has been an active area of research in the treatment of cancer and infectious diseases. Here is the latest research on STING receptor agonists.

Microbicide

Microbicides are products that can be applied to vaginal or rectal mucosal surfaces with the goal of preventing, or at least significantly reducing, the transmission of sexually transmitted infections. Here is the latest research on microbicides.