Multifunctional Alternating “Bitter-Sweet” Macromolecular Architecture

Abstract

The design and synthesis of a multifunctional macromolecular architecture featuring alternating cholic acid (CA) and glucose pendants in a polymer side-chain is reported. The target architecture was prepared by reversible addition–fragmentation chain-transfer copolymerization of styrene-conjugated CA (the bitter monomer) and acetyl-protected glucose appended maleimide (the sweet monomer) using the polyethylene glycol-conjugated chain transfer agent. Removal of the acetates resulted in amphiphilic “bitter-sweet” alternating copolymers that were self-assembled in aqueous media having CA containing bitter core and sugar-coated sweet shell. Dynamic light scattering measurements in water, field emission scanning electron microscopy, and transmission electron microscopy confirmed the formation of 40 to 75 nm sized micellar nanoscaffolds, depending on the chain-length of the copolymers. The nanoparticles successfully encapsulated hydrophobic molecules as witnessed via fluorescence spectroscopy using Nile red as an exemplary guest. Interestingly, the alternating copolymer recognized β-cyclodextrin (β-CD) through the formation of inclusion complexes with lateral cholate moieties in the polymer as evident from 2D NMR and nuclear Overhauser effect experiments. It is worth noting that the polymer and its inclusion complex were found to be capable of recognizing Concanavalin A (Con A), as shown by turbidimetric assay and isothermal titration calorimetry. Interestingly, the inclusion complex of the alternating copolymer showed significantly higher autofluorescence in the presence of Con A with respect to that of un-complexed one. Thus, the present study offers a simple way to prepare a multifunctional alternating copolymer having hydrophobic molecule encapsulation, inherent fluorescence, inclusion complex formation with β-CD, and lectin recognition capabilities.