Fragmentable Polycationic Materials Based on Anchimeric Assistance

A new family of modular, fragmentable oligo- and polycations has been developed based on the reactions of 9-thiabicyclo[3.3.1]dichloride and related compounds with substituted dipyridyl nucleophiles by an anchimeric assistance mechanism. Each bond-forming event in this condensation polymerization process generates a positive charge in the main chain. Product lengths were found to be dependent on the reactivity of the electrophile, which was tunable by changing the nature of the leaving group β to sulfur. The monomers were easily synthesized, and the resulting readily available polymers were found to be highly efficient binders of nucleic acid. They exhibited properties of cytotoxicity and DNA transfection expected of such polycationic materials, but with interesting structure-activity differences that remain to be explored. The polycations decomposed by hydrolysis at rates dependent on the leaving group ability of the pyridyl unit, which correlated roughly with the pK_a of its conjugate acid. Polymer decomposition occurs simultaneously throughout the length of the chains, rather than from the ends; the decomposition products were tested and found to be only minimally toxic to cultured cells.