Enhanced Extraction of Phenobarbital from Serum with a Designed Artificial Receptor

Abstract

The primary goal of this work was to determine whether artificial receptors that function on the basis of molecular recognition have analytical capabilities. As an example of such a receptor, we have chosen one directed toward barbiturates. Chloroform enriched with this artificial receptor (1 mM) can extract more than 90% of the phenobarbital from a 20 microM phenobarbital solution in human control serum using a volume ratio (organic/serum) as small as 0.5. In the absence of this receptor, the volume ratio must be greater than 10 to achieve similar extraction efficiencies. In addition to volume ratio, the role of pH, receptor concentration, and solvent type are discussed. The experimental results are found to be in good agreement with predictions based on chemical equilibria. Through the use of this and other similar receptors, the amount of organic solvent used in extractions can be minimized.

Receptor‐attached amphiphilic terpolymer for selective drug recognition in aqueous solutions

“…The diminished binding for the later, was attributed to either lack of hydrogen bonding sites, or to weaker hydrogen bonding. Specifically, mephobarbital lacks one hydrogenbonding site and thiobarbital has a sulfur instead of an oxygen atom, a weaker hydrogen bond acceptor (Chang and Hamilton, 1988;Chang et al, 1991b;Valenta et al, 1994).…”

“…The barbiturate receptor, initially developed by Hamilton (Chang and Hamilton, 1988;Tecilla et al, 1990;Chang et al, 1991a) serves as an example of a highly specific artificial receptor that is primarily based on hydrogen bonding interactions. It is designed to form stable complexes with the barbiturates through six hydrogen bonds with a binding constant, in non-polar solvents such as CH 2 Cl 2 and CHCl 3 , as high as 10 5 À10 6 M À1 (Chang et al, 1991a;Valenta et al, 1994). Similar to the barbiturate receptor, there is a variety of other artificial receptors as well as small bioactive molecules for which receptors can be designed, for biomedical applications.…”

Photo-induced processes in dendrimers

“…Since then several papers appeared reporting on its ability to subtract barbiturates from serum [34,35], its use as a model for enzyme catalysis [36][37][38], as a building block in supramolecular materials [39,40], and as a receptor in photoactive hydrogen bond-based assemblies [41,42]. From these studies, it was clear that the receptor can be a powerful tool to create stable supramolecular assemblies with barbiturates, even in solvents that are competitive for the receptor site [43].…”

High-Throughput Phase-Distribution Method to Determine Drug-Cyclodextrin Binding Constants

“…There are also a few reports using phase‐distribution methods to determine binding constants for CD complexes 24, 25. Although high‐throughput protein binding assays are developing rapidly,26, 27 this technique has not extended its application to the determination of drug‐CD complexation or drug–small molecule interactions 28, 29…”