Amidophenol-modified amphiphilic calixarenes: synthesis, interfacial self-assembly, and acetaminophen crystal nucleation properties.

Three amidophenol-modified calixarenes have been produced reacting the parent 5,11,17,23-tetracarboxy-25,26,27,28-tetradodecyloxycalix[4]arene with o-, m-, and p-aminophenol. The produced amphiphiles have been shown to form stable monomolecular Langmuir layers on water. Working on subphases containing 1 mM acetaminophen (APAP), it has been demonstrated that the produced amphiphiles interact with this active pharmaceutically ingredient (API) with a relevant preference for the para-derivative that possesses in its structure substituents that are analogous to the target. Working at supersaturating concentrations of APAP, it has been demonstrated that the so-produced calixarene Langmuir monolayers do favor crystallization of APAP (polymorph I), with a clear effect of the packing density of the amphiphile at the interface on the quantity of produced crystals. Monolayers of the para-derivative have been transferred on solid substrates using the Langmuir-Blodgett technique; the so-produced ultrathin films have been shown to initiate surface crystal nucleation of APAP. The produced solids have been analyzed by single-crystal X-ray crystallography and shown to preferentially grow in the [010] direction.

Para-carboxy modified amphiphilic calixarene, self-assembly and interactions with pharmaceutically-relevant molecules.

The self-assembly properties of the amphiphilic 5,11,17,23-tetra-carboxy-25,26,27,28-tetradodecyloxycalix[4]arene have been investigated at the air-water interface as monomolecular Langmuir layers and in water. The interactions of this amphiphile with salicylic acid (SA), acetyl-salicylic acid (ASA) and acetaminophene (APAP) have been studied at the air-water interface by means of the Langmuir balance technique. It has been demonstrated that the calix-arene molecules, when self-assembled as Langmuir monolayers, have the ability to interact with all the tested compounds. While APAP causes a stabilization of the monolayer, ASA and SA cause a slight loss of stability and a drastic change of the compressibility of the monolayer. The study of the self-assembly properties of the title compound in water revealed that this amphiphile can be self-assembled as solid lipid nanoparticles (SLNs). The atomic force microscopy investigations of the colloidal suspension, spread on a solid surface and dried, revealed the coexistence of the SLNs with layered structures.