Tethered non-ionic micelles: a matrix for enhanced solubilization of lipophilic compounds

Abstract

A specific mechanism for tethering micelles composed of non-ionic detergents is presented. The mechanism does not require any precipitant, high ionic strength or temperature alterations. Rather, it relies on complexes between hydrophobic chelators embedded within the micelle and appropriate metal cations in the aqueous phase, serving as mediators. The approach was applied to: (i) four non-ionic detergents (tetraethylene glycol monooctyl ether (C8E4), n-dodecyl-β-d-maltoside (DDM), octyl β-d-1-thioglucopyranoside (OTG), and n-octyl-β-d-glucopyranoside (OG)), (ii) two hydrophobic chelators (bathophenanthroline and N-(1,10-phenanthrolin-5-yl)decanamide, Phen-C10) and (iii) five transition metals (Fe2+, Ni2+, Zn2+, Cd2+, and Mn2+). The mandatory requirement for a hydrophobic chelator and transition metals, capable of binding two (or more) chelators simultaneously, was demonstrated. The potential generality of the mechanism presented derives from the observation that different combinations of [detergent:chelator:metal] are able to induce specific micellar clustering. The greater solubilization capacity of tethered-micelles in comparison with untethered micelles was demonstrated when the water insoluble aromatic molecule fluorenone (8 mM = 1.44 mg mL-1) and two highly lipophilic antibiotics: chloramphenicol (5 mM = 1.62 mg mL-1) and tetracycline (1.5 mM = 0.66 mg mL-1) were solubilized - only when the micelles were tethered.