Complexation of Achiral Calixarenes with Chiral Pharmaceutical Substances: A Circular Dichroism Study

Chamseddin      Chamseddin; Thomas      Jira

Abstract

Calixarenes (CAs), with their unique three-dimensional surface, are one of the best known host molecules along with cyclodextrins, and crown ethers. However, these compounds have been less studied compared to cyclodextrins. The present work is devoted to the evaluation of the ability of eleven different calixarenes to form host-guest complexes with eleven pharmaceutical relevant substances (chiral active pharmaceutical ingredients/APIs) in different solutions (acetonitrile, methanol and water), including comparisons between water-soluble calixarenes and three pharmaceutically relevant cyclodextrins (α-, β- and γ-cyclodextrins) by means of circular dichroism spectroscopy (CD). The obtained CD spectra provided the absolute configuration of the chiral APIs, as well as of the interactions with host-molecules. An attempt to understand the complexation mechanism of calixarenes was undertaken based on the CD-spectra of the drugs with different host macrocycles. These results indicate that calixarenes could serve as candidate host molecules in the pharmaceutical researches due to their versatility and the ease of adding different moieties to their upper and/or lower rim, which makes it easier to change the affinity of these cyclooligomers towards target molecules and/or increase the solubility of the calixarenes.

Keywords: Active Pharmaceutical Ingredients (APIs), Calixarenes (CA), Circular Dichroism (CD), Cyclodextrins, Host-guest omplexation, Macrocyclic Molecules, macrocycles, API, methanol, cyclooligomers