Chiral Interactions of the Drug Propranolol and α₁-Acid-Glycoprotein at a Micro Liquid–Liquid Interface

Abstract

The investigation of chiral interactions of drugs with plasma proteins is of fundamental importance for drug efficacy and toxicity studies. In this paper, we demonstrate a simple liquid-liquid interface procedure for investigating chiral interactions. Chiral discrimination of the enantiomers of a basic drug, propranolol, was achieved at a micro liquid-liquid interface, using α(1)-acid-glycoprotein (AGP) as a chiral acute phase plasma protein. When the protein is added to an aqueous phase containing the enantiomers of propranalol hydrochloride, the binding of (S)- and (R)-propranolol hydrochloride to the protein results in a decrease in the cyclic voltammetry (CV) and differential pulse voltammetry (DPV) current responses corresponding to the decrease in transfer of propranolol at an aqueous-1,2-dichloroethane interface. This decrease is a consequence of the complexation of the drug and the protein. The complex drug-protein does not transfer across the interface nor changes the transfer potential of the uncomplexed form of propranolol enantiomers. The bound concentration of propranolol enantiomers in the presence of AGP was found to be greater for (S)-propranolol than (R)-propranolol for solutions containing constant concentrations of AGP (50 μM). Scatchard analysis yielded association constants of 2.7 and 1.3 × 10(5) M(-1) for (S)- and (R)-propranolol, respectively.

Interaction of cyanidin-3-O-glucoside with three proteins

“…According to the Scatchard model, if the Scatchard plot is a straight line, this could be an indication that all the binding sites have the same affinities and a simple binding reaction occurs. If the plot is curved, it demonstrates that it binds to more than one type of site or if there is co-operativity in binding (Lopes & Kataky, 2012). The Scatchard model was used to calculate the value of f u :…”

Liquid/Liquid Interfaces, Electrochemistry atUpdate based on the original article by Frédéric Reymond, Hubert H. Girault,Encyclopedia of Analytical Chemistry, © 2000, John Wiley & Sons, Ltd

“…The complexation of one enantiomer of protonated propranolol by a glycoprotein in a physiological buffer decreased the observed current for IT across ITIES, as the complexed species does not transfer, allowing the determination of the association constants for both enantiomers. (159) …”

Electroanalytical Opportunities Derived from Ion Transfer at Interfaces between Immiscible Electrolyte Solutions

“…The transfer potential of propranolol is within the range easily available at W/DCE and W/DCH interfaces, which explains its wide interest as a demonstrator compound for drug analyses at the ITIES. For example, Lopes and Kataky [91] reported the use of electrochemistry at a micro-ITIES to study chiral interactions of propranolol enantiomers with the protein alpha1-acid-glycoprotein. In this case, the drug enantiomers bind to the protein in the aqueous phase and only unbound drug is detected by ion-transfer voltammetry.…”