Nanostructured Polyelectrolyte Complexes Based on Water-Soluble Thiacalix[4]Arene and Pillar[5]Arene: Self-Assembly in Micelleplexes and Polyplexes at Packaging DNA

Abstract

Controlling the self-assembly of polyfunctional compounds in interpolyelectrolyte aggregates is an extremely challenging task. The use of macrocyclic compounds offers new opportunities in design of a new generation of mixed nanoparticles. This approach allows creating aggregates with multivalent molecular recognition, improved binding efficiency and selectivity. In this paper, we reported a straightforward approach to the synthesis of interpolyelectrolytes by co-assembling of the thiacalix[4]arene with four negatively charged functional groups on the one side of macrocycle, and pillar[5]arene with 10 ammonium groups located on both sides. Nanostructured polyelectrolyte complexes show effective packaging of high-molecular DNA from calf thymus. The interaction of co-interpolyelectrolytes with the DNA is completely different from the interaction of the pillar[5]arene with the DNA. Two different complexes with DNA, i.e., micelleplex- and polyplex-type, were formed. The DNA in both cases preserved its secondary structure in native B form without distorting helicity. The presented approach provides important advantage for the design of effective biomolecular gene delivery systems.

PAMAM-calix-dendrimers: Synthesis and Thiacalixarene Conformation Effect on DNA Binding

“…In this regard, we first applied the UV-Vis spectroscopy method to establish the possibility of interaction between the compounds G1 ( G1-cone , G1-paco, and G1-1,3-alt ) and DNA. We have chosen salmon sperm DNA, which is widely used as a model biomolecule [ 6 , 17 , 18 ]. The amine groups of the studied compounds G1 were converted into the cationic form ( G1-HCl ) by reaction with hydrochloric acid in order to increase the affinity to the biopolymer.…”

“…The amine groups of the studied compounds G1 were converted into the cationic form ( G1-HCl ) by reaction with hydrochloric acid in order to increase the affinity to the biopolymer. DNA has maximum absorption in the region up to 300 nm [ 17 , 18 ]. The fact that the synthesized compounds have absorption due to π-π* transitions of aromatic rings of the platform and n-π* transitions of carbonyl groups in the same range (200–315 nm) complicated the study [ 26 ].…”

“…However, with an increase in the concentration of the compounds G1-HCl (3.33 × 10 −5 M and 3.33 × 10 −6 M), the spectra started being significantly complicated because of an increase in the baseline of the spectrum in the long-wavelength region. This additionally indicated that the association of the macrocycles with the biomolecule resulted in the formation of the nanoparticles ( Figures S28–S32 ) [ 18 , 44 ]. Such character of spectral changes is common for biopolymers when they bind by macrocyclic compounds [ 45 , 46 ].…”

2D Monomolecular Nanosheets Based on Thiacalixarene Derivatives: Synthesis, Solid State Self-Assembly and Crystal Polymorphism

“…In this work, we propose to use a macrocyclic fragment of thiacalix[4]arene to create structures capable of forming mono- and bimolecular layers. The advantage of this platform is the presence of various stereoisomeric forms [ 19 , 20 , 21 , 22 , 23 , 24 , 25 ] allowing geranyl fragments to be strictly oriented in the space. Thiacalix[ 4 ]arenes are conformationally flexible molecular platforms that allow varying the size of the internal cavity, the number, nature and the spatial arrangement of binding sites.…”

“…There are examples of thiacalixarene derivatives for the development of synthetic receptors for biologically important anions [ 22 ] and dopamine [ 23 ], which can be used in biomimetic materials, diagnostic agents and in the treatment of neurodegenerative diseases. Mention should also be made about polyplexes based on thiacalixarene derivatives, which are used for DNA packaging and have promising applications in biomolecular delivery systems and long-term storage of human genetic material [ 25 ]. Among other things, the controlled (smart) formation of polymorphs based on thiacalixarene derivative are also known [ 30 ].…”