Effect of preorganization and amphiphilicity of calix[4]arene platform on functional properties of viologen derivatives

• Novel cavitands of calix[4]resorcinols with viologen fragments were synthesized. • Self-assembly of cavitands was evaluated relative to the hydrophobicity of their lower rim. • The toxicity of macrocycles is lower than those of surfactants similar in structure. A series of novel amphiphilic cavitands of calix[4]resorcinols with viologen fragments on the upper rim synthesized through a combination of viologen moieties and amphiphilic macrocyclic skeleton is reported. The influence of their structure on self-assembly, solubilization and biological properties was found. The driving force of the self-assembly of the synthesized macrocycles is the hydrophobic interactions of their hydrocarbon chains through additional π-stacking interaction between the aromatic rings of neighboring macrocycle molecules, which is enhanced with an increase in the length of the alkyl chains on the lower rim. The lower hemotoxicity of long-chain viologen macrocycles, relative to viologen surfactant, the ability to bind therapeutic molecules and the selective cytotoxic activity to tumor cells are explicit references to viologen derivatives of calix[4]resorcinols as promising drug nanocontainers.