Tunable nanostructures by directional assembly of donor–acceptor supramolecular copolymers and antibacterial activity

Abstract

This manuscript reports supramolecular copolymerization of amphiphilic donor (D) and acceptor (A) units and their antibacterial activity. The donor unit (Py-1) contains a pyrene chromophore attached to a quaternary ammonium group by an amide linker. In the acceptor unit (NDI-1), a naphthalene-diimide (NDI) chromophore is attached to a hydrophilic non-ionic wedge and a benzamide group on its two opposite arms. In aqueous medium, Py-1 and NDI-1 produce micelle like nanoparticles and a fibrillar gel, respectively. Contrastingly, their 1 : 1 mixture shows polymersome like assembly in which the membrane is constituted of alternating D–A stacking stabilized by charge-transfer (CT) interactions and H-bonding among the amide groups. H-Bonding further gives unidirectional lateral orientation of the two chromophores and also regulates the direction of curvature so that all the cationic head groups are displayed on the exofacial polymersome surface. Such cationic D–A supramolecular polymersomes exhibit good bactericidal activity selectively against Gram positive bacteria over Gram negative bacteria. The spherical polymersome assembly gradually adopted a tubular morphology without disrupting the alternating D–A stacking mode, but it significantly reduced the antibacterial activity. By changing the D/A ratio, the surface charge density, hydrophobicity and morphology of the supramolecular copolymers could be tuned systemically, which had a strong impact on the antibacterial activity and selectivity. Addition of 5–10 mol% of NDI-1 to Py-1 changed the morphology from nanoparticles to polymersomes with the most optimized combination of cationic charge density and hydrophobicity, which resulted in producing a lethal antibacterial system (MIC value 16 μg mL−1) selectively against Gram positive bacteria. Mechanistic investigation indicated a membrane disruption pathway of cell killing. No combination of Py-1 and NDI-1 exhibited hemolysis activity up to 1000 μg mL−1 confirming their selective action against the bacterial membrane over the mammalian cell membrane.