Effect of L‒tryptophan and L‒phenylalanine residues in the pillar[5]arene structure for the formation of fluorescein containing nanoparticles and imparting fluorescence properties

pH‒Sensitive systems with fluorescent properties based on polyfunctional macrocyclic pillar[5]arene platforms represent a promising approach for designing drug delivery complexes and imaging markers. Herein, we propose and develop an approach to synthesis of pillar[5]arene derivatives with amino acids residues (L‒tryptophan and L‒phenylalanine) and obtaining fluorescein containing nanoparticles with fluorescein properties and its subsequent release depending on the pH. Fluorescein containing nanoparticles were obtained by mixing solutions of synthesized pillar[5]arenes and fluorescein. Dynamic light scattering and transmission electron microscopy were used to determine the size and shape of the obtained particles. The size of spherical nanoparticles was 79÷1 and 92÷1 nm for particles based on pillar[5]arene with L‒phenylalanine and L‒tryptophan residues respectively. The ability to form complexes and associates with fluorescein by synthesized macrocycles was studied by electron UV–vis and fluorescence spectroscopy, two–dimensional ¹H–¹H NOESY NMR spectroscopy and dynamic light scattering. Pillar[5]arene with L‒phenylalanine moieties more efficiently binds fluorescein (lgK_a = 3.92) compared with pillar[5]arene with L‒ tryptophan moieties (lgK_a = 2.94). The two systems exhibited different fluorescence mechanisms AIE for the mixed particles based on pillar[5]arene with L‒ phenylalanine residues and ACQ ‒ for pillar[5]arene with L‒ tryptophan residues. It was found that the fluorescein release was observed only from the associates based on pillar[5]arene with L‒tryptophan residues in the neutral (pH = 7.4) and alkaline (pH = 9.2) solutions. The results of this work may be useful for further research to create targeted drug delivery systems with pH‒controlled release.

The work was supported by Russian Science Foundation (№18-73-10094), https://rscf.ru/project/18-73-10094/