Synthesis of new p-tert-butylcalix[4]arene-based polyammonium triazolyl amphiphiles and their binding with nucleoside phosphates

Abstract

The synthesis of new calix[4]arenes adopting a cone stereoisomeric form bearing two or four azide fragments on the upper rim and water-soluble triazolyl amphiphilic receptors with two or four polyammonium headgroups via copper-catalyzed azide–alkyne cycloaddition reaction has been performed for the first time. It was found that the synthesized macrocycles form stable aggregates with hydrodynamic diameters between 150–200 nm and electrokinetic potentials about +40 to +60 mV in water solutions. Critical aggregation concentration (CAC) values were measured using a micelle method with pyrene and eosin Y as dye probes. The CAC values of tetraalkyl-substituted macrocycles 12a,b (5 µM for both) are significantly lower than those for dialkyl-substituted macrocycles 10a,b (790 and 160 µM, respectively). Premicellar aggregates of macrocycles 10a,b and 12a,b with the dye eosin Y were used for nucleotides sensing through a dye replacement procedure. It is unusual that disubstituted macrocycles 10a,b bind more effectively a less charged adenosine 5'-diphosphate (ADP) than adenosine 5'-triphosphate (ATP). A simple colorimetric method based on polydiacetylene vesicles decorated with 10b was elaborated for the naked-eye detection of ADP with a detection limit of 0.5 mM.

Clear distinction between CAC and CMC revealed by high-resolution NMR diffusometry for a series of bis-imidazolium gemini surfactants in aqueous solutions

“…52,53 Therefore, establishing new methods to reliably evaluate the CAC and CMC values is necessary for synthesizing novel series of improved amphiphiles and their characterization. 52,54,55 Moreover, studding the aggregation process is essential not only in case of surfactants; but also polymers, 56 proteins and peptides. 57 CAC values are also meaningful in some specic applications like in case of amphiphilic molecules for membrane protein stabilization at high dilutions.…”

Calix[4]arene Polyamine Triazoles: Synthesis, Aggregation and DNA Binding

“…One of the most powerful universal reactions, which allows to modify the macrocyclic platform, is the copper-catalyzed azide-alkyne cycloaddition reaction (CuAAC) [ 32 , 33 ]. Previously, we developed a method for the synthesis of di- and tetraarylazide derivatives based on the diazotization of available calix[4]arene di- and tetraamines, followed by substitution of the diazo group by an azide ion [ 34 ]. Carrying out this reaction with calixarene unsubstituted at the lower rim is also of great interest, since free phenolic hydroxyl groups can be post-modified by alkylation, acylation, etc.…”

“…It is noteworthy that the introduction of a triethylammonium fragment into the cavity does not lead to a cone configuration distortion—thus, the pairwise distance between the opposite carbon atoms of C008 is 8.391 Å, as well as the distance between opposite oxygen atoms O003 is 3.657 Å, which is obviously associated with the small size of the azide substituents and the ammonium salt itself, although for the above-mentioned p-tert -butylcalix[4]arene [ 41 ] such coordination causes a distortion of the cone configuration. Another reason for maintaining the undistorted cone configuration is the presence of a cyclic hydrogen bond on the lower rim, while in the tetra-O-butyl calix[4]arene tetraazide [ 34 ] a strong distortion of the configuration is observed—for example, the distance between opposite carbon atoms in this case is 10.051 (between C24 and C10) and 4.018 (between C3 and C17) due to the absence of a hydrogen bond. Additionally, the crystals of macrocycle 3 pack into an interesting cellular structure containing solvent molecules (CH 2 Cl 2 ) in the cells ( Figure 2 ).…”

“…For this, calixarene 6 was synthesized using previously published methodology [ 34 ], including tetra-alkylation with butyl bromide, ipso-nitration, reduction using NH 2 NH 2 in the presence of Ni on silica-alumina, diazotization with following substitution of diazo-groups by NaN 3 and CuAAC reaction with 3-bis[2-( tert -butoxycarbonylamino)ethyl]-propargylamine with following Boc-deprotection. Calixarene 7 with four tetradecyl fragments was synthesized in the same manner using tetradecyl calixareneazide [ 46 ] instead of tetrabutyl one.…”

“…Solvents were purified according to standard methods. 3-Bis[2-( tert -butoxycarbonylamino)ethyl]propargylamine, 25,26,27,28-tetrahydroxycalix[4]arene, 5,11,17,23-tetraazo-25,26,27,28-tetrahydroxycalix[4]arene, 5,11,17,23-tetraamino-25,26,27,28-tetrahydroxycalix[4]arene [ 64 , 65 , 66 ] and 5,11,17,23-tetra(4-((bis(2-(amino)ethyl) amino)methyl)-1H-1,2,3-triazol-1-yl))-25,26,27,28-tetrabutylcalix[4]arene octahydrochloride ( 6 ) [ 34 ] were prepared following literature procedures.…”