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Keywords:

  • barbiturates;
  • amphiphilic polymer;
  • docking studies;
  • molecular recognition;
  • binding model:

Abstract

In the present work, a combination of binding studies and molecular docking were employed to demonstrate drug encapsulation and host–guest chemistry in self-assembled micelles consisting of amphiphilic terpolymers. The terpolymer is composed of poly(3-sulfopropyl methacrylate), as the hydrophilic component, poly(n-dodecyl acrylate), as the hydrophobic component and poly(barbiturate receptor), as the component for drug recognition. The combined approach was tested on four model compounds from the family of barbiturates, phenobarbital, mephobarbital, secobarbital, and thiopental, chosen based on their differential hydrogen bonding capabilities. Drug encapsulation and hydrogen-bonding based recognition within the micellar core of the receptor–terpolymer was demonstrated by micellar electrokinetic chromatography. The resulting trends in the binding affinity of the barbiturates to the receptor–terpolymer, were correlated to the trends obtained from computational docking simulations. This receptor-modified polymeric micelle is intended to serve as a model for the design of novel, versatile, and highly selective molecular scaffolds that will provide suitable environment for host–guest chemistry and act as simplified mimics to more complex biological systems. Copyright © 2011 John Wiley & Sons, Ltd.