Development of a Pillar[6]arene Carboxylic Acid Derivative for the Extraction of a Cationic Protein.

Abstract

Pillararenes are macrocyclic compounds that can have multiple functional groups and can provide a platform to develop multivalent ligands. Herein, a pillar[6]arene carboxylic acid derivative (OctP[6]CH₂COOH) was prepared to extract the cationic protein cytochrome c (Cyt-c) into organic solvents. OctP[6]CH₂COOH was synthesized by the condensation of ethyl 2-(4-octoxyphenoxy) acetate to obtain the pillar[6]arene derivative, followed by alkali hydrolysis. OctP[6]CH₂COOH showed high extractability for Cyt-c, while a monomer analog and a neutral pillar[6]arene ester derivative did not. The lysine-rich protein Cyt-c was selectively extracted using OctP[6]CH₂COOH over other cationic proteins because the complexation was a result of the inclusion of the NH₃⁺ groups of the lysine residues by the macrocyclic molecule. Cyt-c complexed with OctP[6]CH₂COOH partially underwent a structural change and exhibited peroxidase activity in organic solvents. This is the first report of protein extraction using pillararene derivatives that can be applied for the separation and modification of proteins.