Complexation of GdIII with tetra-p-tert-butylthiacalix[4]arenoic acid in micellar media

Abstract

The conditions for the formation of gadolinium(III) complexes possessing high relaxivity with various tetraacid stereoisomers based on p tert butylthiacalix[4]arene in micellar solutions of nonionic surfactants were established. The acid base properties of individual isomers of the ligand were studied by pH metric titration and UV spectroscopy. The composition and stability constants of the solubilized gadolinium(III) complexes with the obtained thiacalixarenes were determined using computer simulation of the NMR relaxation data.Search for high relaxivity metal complexes is one of the most urgent problems in the development of new con trast agents (CAs) for magnetic resonance imaging (MRI), which is a non invasive method for NMR based clinical diagnostics of diseases. 1 At present stable gadolinium(III) complexes with linear and cyclic polyaminopolycarboxy lates are used as CAs. 2 A substantial drawback of these CAs is their low relaxivity factor (3000-5000 L mol -1 s -1 ), which requires the administration of large doses of the drug to the body. Since natural biochemical cycles involv ing Gd 3+ ions are absent, the decrease in the amount of the gadolinium compounds introduced into the body is an important task. This requires the design of contrast agents with high spin lattice relaxivity values (relaxivity is the paramagnetic contribution to the relaxation rate of pro tons of the solvent, R 1 ). 2,3 It is known that one of the methods for increasing the relaxivity of solutions contain ing gadolinium ions is the retardation of their rotation due to the formation of high molecular weight particles (aggregation, complexes) in their composition. 4 It was shown 5,6 than an increase in the relaxivity in solutions of long chain alkyl sulfates in the presence of Gd 3+ ions is caused by the adsorption of the latter on the surface of anionic micelles. The increase in the relaxivity of the gadolinium(III) complex with the diethylenetriaminepen taacetic acid derivative containing the cholesterol moiety as the substituent is due to its self aggregation in wa ter with an increase in the concentration or the incor poration of the complex in mixed aggregates with the non ionic surfactant. 7 Thus, the choice of amphiphilic com pounds capable of self aggregation or incorporation in the composition of mixed aggregates seems to be one of the promising approaches to the design of contrast pre parations.From this point of view, metacyclophanes, in particu lar, calixarenes, whose ability to complexation and hydro philic-lipophilic balance can be varied in a wide range, 8-11 are very promising ligands for chelating rare earth met al ions, including gadolinium(III). 12,13 Meanwhile, in a few known works, 14,15 calixarenes with insufficient lipo philicity were used to design potential contrast agents. However, the influence of the ligand conformation on the stability and relaxation parameters of their complexes with Gd III was not examined. The purpose of the present study is to reveal the influence of the spatial arrangement of the func...

Recent developments of thiacalixarene based molecular motifs

“…The tetraacid stereoisomers 83-85 91 bind Gd 3+ ions efficiently and exhibit high relaxivity in micellar solutions of non-ionic surfactants (Fig. 15).…”

Design of High-Relaxivity Polyelectrolyte Nanocapsules Based on Citrate Complexes of Gadolinium(III) of Unusual Composition

“…NMR relaxation measurement is highly informative tool not only for the investigation of paramagnetic cation complexes (including development of new types of CAs for MRI), but also for the study of nanosized objects in solutions. Features of the mechanism of proton relaxation in gadolinium solutions (an increase in the relaxivity due to the slow-down of rotation of Gd(III) ions bound to nanoparticle) revealed not only aggregation in the solutions of surfactants [22,23] or lipophilic macrocycles [24,25], but also the binding of cations with polymers [26], or graphene oxide [27,28]. In addition, the authors of this current paper have previously discovered that metal ion complexes can form associates with oppositely charged ions of surfactants, macrocycles, or polymers [29][30][31][32].…”