Novel Cationic Bolaamphiphiles for Protein and DNA Binding, Gene Delivery, and Antimicrobial Applications

In this study, we have designed and developed a cationic bolaform C₁₂-(2,3-dihydroxy-N, N-dimethyl-N-(2-ureidoethyl)propan-1-aminium chloride)₂ (C₁₂(DDUPAC)₂) that is derived from biocompatible molecules. The bolaform C₁₂(DDUPAC)₂ has hydroxyl (OH) functionality at both the cationic head groups. The impact of head group structure on the self-assembly and effectiveness of gene transfection and antimicrobial activity was investigated and compared with that of the hydrochloride salt C₁₂-(N, N-dimethyl-N-(2-ureidoethan-1-aminium chloride)₂ (C₁₂(DUAC)₂) of its precursor molecule. The formation of spherical as well as rod-like self-assembled structures was found to occur above a relatively low critical aggregation concentration (CAC) by the bolaforms. The results of calorimetric measurements demonstrated thermodynamically favorable aggregation in water. Interaction studies of the cationic bolaforms with the calf thymus DNA revealed stronger binding of C₁₂(DDUPAC)₂ in comparison to C₁₂(DUAC)₂, which explained higher in vitro gene transfection efficiency of C₁₂(DDUPAC)₂ than C₁₂(DUAC)₂. Both bolaforms interact weakly with the bovine serum albumin protein. MTT-based in vitro cytotoxicity assay was performed and both bolaforms were found to have marginal cytotoxicity. Further, both bolaforms exhibit advantageous antibacterial activity against E. coli and potent antifungal activity against Fusarium oxysporum at high dosages.