Synthesis and self-assembly of highly substituted β-Cyclodextrin derivatives: Impact of alkenyl chain length and degree of substitution

Abstract

Amphiphilic β-cyclodextrin derivatives (CDmod5Cn) with high degrees of substitution (DS = 5) were synthesizedand characterized to investigate the role of alkenyl chain length in supramolecular self-assembly and interfacialbehavior. Derivatives with alkenyl chain lengths of 10, 12, and 14 carbon atoms were synthesized using sodiumcarbonate as an effective heterogeneous catalyst. Comprehensive physicochemical characterization, employingsurface tension measurements and microscopy, revealed differentiated molecular behaviors in aqueous media.Notably, surface tension analysis revealed complex interfacial dynamics, with the C12 derivative containing fivetwelve‐carbon hydrocarbon chains and exhibiting exceptional surfactant properties that significantly exceededthose of longer-chain analogs. Spontaneous formation of monodisperse vesicles (130–150 nm diameter withnarrow polydispersity) was confirmed by DLS and TEM, demonstrating high uniformity in supramolecular or­ganization. Interactions between CDmod5Cn and molecular probes were explored through induced circular di­chroism (ICD) spectroscopy and fluorescence measurements. Despite the partial occupation of the cyclodextrincavity by the alkenyl chains, these amphiphilic β-cyclodextrins retained their remarkable ability to form host-guest complexes. The ICD spectra displayed clear signals characteristic of effective molecular recognition,while fluorometric analysis offered complementary confirmation of these binding interactions. This study en­hances our understanding of the molecular recognition capabilities of amphiphilic β-cyclodextrins and positionCDmod5Cn as promising candidates for pH-responsive drug delivery and supramolecular sensors.