Fragmentable Polycationic Materials Based on Anchimeric Assistance

Abstract

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.

Design of polymers for siRNA delivery: Recent progress and challenges

“…[192] Polymerization of 9-thiabicyclo[3.3.1]-dichloride with tris(pyridine) trinucleophiles generated a class of positively charged and branched polymers (Figure 7A). [193] These polymers exhibited high siRNA binding, and could be degraded into small molecule diols and pyridines under hydrolysis at 37 • C. The degradation of polymer scaffold efficiently promoted siRNA release and gene silencing. The responsive polymers can be fabricated by crosslinking of cationic polymers using dynamic covalent linkages.…”

“…(A) Schematic representation of condensation polymerization and depolymerization of BCN-based hyperbranched polycations. Reproduced with permission 193. Copyright 2018, ACS.…”

Efficient Synthesis of a New Family of 2,6-Disulfanyl-9-selenabicyclo[3.3.1]nonanes

“…The biochemical potential of 9-selenabicyclo[3.3.1]nonanes has not yet been revealed; however, it is known that its sulfur and nitrogen analogues exhibit a variety of biological activities [ 17 , 18 , 19 , 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 ].…”

“…Novel polycationic materials based on 9-thia-, 9-aza-, and 9-selena[3.3.1]bicyclononanes have been synthesized and proposed as DNA-transfecting polymers [ 21 , 22 , 23 ]. An important desirable feature of DNA-transfecting polymers is the ability to degrade into non-toxic components after cellular uptake of a DNA-polymer complex.…”

Thiabicyclononane-Based Antimicrobial Polycations

“…Many exhibit modest molecular weights (6000−20 000 g/ mol) and broad molecular weight distributions, but interesting antibacterial function. 16−18 We have previously reported the synthesis of cationic oligomers and polymers (3) 19 based on the rapid substitution chemistry of bicyclo[3.3.1]nonane (BCN) electrophiles such as 1 with dipyridyl nucleophiles (2) by an anchimeric assistance mechanism (Figure 1). 20,21 Each bond-forming event generates a positively charged pyridinium center in the main chain.…”