Determination of Lipophilicity by Gradient Elution High-Performance Liquid Chromatography

Abstract

A novel method for the determination of lipophilicity using a simple HPLC protocol based on gradient elution chromatography is presented and compared to the common isocratic log k'(w) procedure. Linear relationships with high correlation coefficients between both methods for biologically active nucleosides and cyclic nucleotides as well as for environmentally relevant aromatic hydrocarbons were found. A mathematical fit to support the empirically determined linear relationship is presented. It is shown that the observed relationship between log k'(w) and the apparent capacity factor (k'(g)) determined by gradient elution is derivable by theoretical considerations as well. Since the gradient method is much less time-consuming compared to other procedures, it represents a convenient alternative for determining lipophilicity data in the future.

Hydrolysis products of cAMP analogs cause transformation ofTrypanosoma bruceifrom slender to stumpy-like forms

“…Sp-8-pCPT-2Ј-O-Me-cAMPS was found to inhibit the catalytic domain of TbrPDEB2, with a K i of 570 Ϯ 3 nM (n ϭ 4), more potently than 8-pCPT-2Ј-O-Me-cAMP did. This compound is more membrane-permeable than 8-pCPT-2Ј-O-MecAMP (24). If the inhibition of proliferation observed was attributable to PDE inhibition, it would be expected that this compound would show similar effects as 8-pCPT-2Ј-O-MecAMP.…”

Presynaptic effectors contributing to cAMP-induced synaptic potentiation inDrosophila

“…FKL stock solution was dissolved in dimethyl sulphoxide (DMSO; Sigma); the final concentration of DMSO did not exceed 0.1% in the preparation chamber. The Epac agonist 8-CPT-2-Me-cAMP (8-CPT) was obtained from BioLog and is highly membrane permeant as indicated by the lipophilicity of cAMP agonists (Krass et al, 1997). The Epac antagonist Brefeldin A (BFA) was purchased from Calbiochem.…”

Estimation of alkane–water logP for neutral, acidic, and basic compounds using an alkylated polystyrene-divinylbenzene high-performance liquid chromatography column

“…According to chromatographic theory, there is not a precisely linear relation between these terms, however for certain HPLC methods the deviation from linearity may be negligible. In these cases, log k can be expected to be proportional to k g with a correlation coefficient higher than 0.985 [37]. In the PRP-C18 acetonitrile system, the linear relation between gradient t R and isocratic log k 50 is evident (Fig.…”

“…There has been an exploration of the mathematical relationship between the log of the isocratic retention factor and a parameter called k g (the apparent gradient retention factor), which is itself a linear transformation of t R [37]. According to chromatographic theory, there is not a precisely linear relation between these terms, however for certain HPLC methods the deviation from linearity may be negligible.…”