Amphiphilic calixresorcinarene associates as effective solubilizing agents for hydrophobic organic acids: construction of nano-aggregates

Abstract

Here we represent the first example of the formation of mixed nanoscale associates, constructed from amphiphilic calixresorcinarenes and hydrophobic carboxylic acids including drugs. The amidoamino-calixresorcinarene self-associates effectively solubilize hydrophobic carboxylic acids - drugs such as naproxen, ibuprofen, ursodeoxycholic acid and aliphatic dodecanoic acid - with the formation of the mixed aggregates with the macrocycle/substrate stoichiometry from 1/1 to 1/7. The ionization of organic acids and the peripheral nitrogen atoms of the macrocycles with the subsequent inclusion of hydrophobic acids into the macrocycle self-associates is the driving force of solubilization. In some cases, this leads to the co-assembly of the macrocycle polydisperse associates into supramolecular monodisperse nanoparticles with the diameter of about 100 nm. The efficiency of drug loading into the nanoparticles is up to 45% and depends on the structure of organic acid. The dissociation of the mixed aggregates and release of organic acid are attained by decreasing pH.

Ab initio design of drug carriers for zoledronate guest molecule using phosphonated and sulfonated calix[4]arene and calix[4]resorcinarene host molecules

“…Their abilities to form host-guest complexes make it possible to use in nonlinear optical chromophores, ion receptors, ion selective electrodes and molecular recognition devices, [14][15][16] but they have attracted much more interest in drug design and delivery. [17][18][19][20] Indeed, the amphiphilic calixarenes, containing two rims as antipodal blades (hydrophobic and hydrophilic segments linked by noncovalent bond), can serve as carriers for many guest drugs employing the host-guest interaction.…”

Preliminary Investigation of Organocatalyst Activity Based on C‐Arylcalix[4]‐2‐Methylresorcinarene Sulfonic Acid Materials for Biodiesel Production

“…12 However, the catalytic activity of calix [4]pyrogallolarene sulfonic acids (up to 91.9%) was not significantly different from that of calix [4]arene sulfonic acids. Deoxygenation of calix [4]pyrogallolarenes provided calix [4]resorcinarenes, which has unique applications for phase transfer catalyst 21,22 and is a suitable host compound for carboxylic acids 23,24 . Calixresorcinarenes have been evaluated as a catalyst for some organic reactions such as one-pot synthesis of coumarin 25 , nucleophilic substitution of phosphorus acid esters 26 , ring-opening reaction of triaryl-pyrylium 27 , and conversion of epoxide to azidohydrin derivatives 28 .…”

Features of Solution Behavior of Polymer Stars with Arms of Poly-2-alkyl-2-oxazolines Copolymers Grafted to the Upper Rim of Calix[8]arene

“…The use of calixarene derivatives as the branching center of star-shaped polymers is due to bringing the unique ability of calix[n]arenes to complex formation with low molecular weight organic compounds [ 28 , 29 , 30 ]. Accordingly, a number of calix[n]arene derivatives with functionalization with low molecular weight fragments have been proposed for use in targeted drug delivery systems [ 31 , 32 , 33 , 34 , 35 , 36 ]. Calixarenes with polymer arms have also been obtained [ 25 , 37 ].…”