Cationic Bottlebrush Polymers from Quaternary Ammonium Macromonomers by Grafting‐Through Ring‐Opening Metathesis Polymerization

Abstract

Cationic bottlebrush homopolymers are polymerized using a grafting‐through approach by ring‐opening metathesis polymerization (ROMP) to afford well‐defined polymers. Quaternary ammonium macromonomers (MMs) are prepared by quaternizing tertiary amine MMs synthesized by reversible addition‐fragmentation chain transfer (RAFT) polymerization. The quaternary ammonium MMs undergo ROMP to target molecular weights (Mn = 30 000–100 000 g mol−1) and a low dispersity (Đ = 1.10–1.30). Halide‐ligand exchange between the third generation Grubbs catalyst (G3) and halide counter ions (bromide and iodide ions) of MMs changes the catalyst activity throughout ROMP, causing it to deviate from pseudo‐first order kinetic behavior; however, the polymerization still follows controlled behavior without significant catalyst termination. Increasing steric bulk of the MMs decreases the polymerization rate as well. Amphiphilic block copolymers are synthesized by sequential polymerization of quaternary ammonium MMs and polystyrene (PS) MMs. Using a PS macroinitiator affords block copolymers with lower Đ values as compared to the less active cationic macroinitiator.

Cationic Bottlebrush Polymers Outperform Linear Polycation Analogues for pDNA Delivery and Gene Expression

“…The polymers are created through polymerization of macromonomers (MM). The physical properties of such systems depend on the molar mass, degree of polymerization, and composition of both the side-chains and backbone. , The unique ability to synthetically alter and isolate these variables by using orthogonal polymerization techniques such as RAFT polymerization − and ring-opening metathesis polymerization (ROMP) − can be harnessed by different synthetic methods, including grafting-through and grafting-from techniques. − This synthetic platform also allows for the production of high molecular weight polymers while having relative control over dispersity. Bottlebrush polymers have shown efficacy for delivery of small molecule therapeutics by both covalent binding and noncovalent sequestration of the payload. − Only a few examples of using bottlebrush polymers for nucleic acid delivery have been documented to date.…”

Water-Stable Thin-Film Nanostructures from Amphiphilic Cationic Bottlebrush Block Copolymers by Grafting-through Ring-Opening Metathesis Polymerization

“…As previously reported, sequential polymerization of NB-PS and then NB-PDMH MMs afforded well-defined architectures of BBCPs with low D̵ . 29 A library of BBCPs was generated by tuning the feed ratios of NB-PS to NB-PDMH to G3 (NB-PS/ NB-PDMH/G3), as summarized in Table 1. 1 H NMR spectra showed successful ROMP of PS 17 -b-PDMH as evidenced by the disappearance of the norbornenyl olefin peak (NB) at 6.07 ppm and the generation of vinyl peaks at 4.9−5.5 ppm, corresponding to the formed polynorbornene backbone (Figure 1A).…”

“…The third-generation Grubbs catalyst, (H 2 IMes-pyr) 2 (Cl) 2 RuCHPh (G3), polystyrene (NB-PS) with DPs of 17 and 39, and norbornene-functionalized poly-(dimethylhexyl bromo)ethyl acrylate (NB-PDMH) with a DP of 14 were synthesized according to the previously reported procedures. 29 Characterization. Number-average MW (M n ) and dispersity values (D̵ ) were obtained from size exclusion chromatography (SEC) analysis using a 1260 Agilent Chromatograph, three Phenogel (Phenomenex) columns in series with pore sizes of 50, 10 3 , and 10 6 Å, and a refractive index detector with linear polystyrene (PS) standards.…”

“…26−28 Although direct creation of BBCPs with a high density of charged constituents in the polymer chains is challenging, our recent publication reported the first successful methodology to synthesize well-defined BBCPs by a graftingthrough approach, yielding a densely charged macromolecular brush. 29 These amphiphilic BBCPs were hypothesized to be able to form phase-separated morphologies in thin films and that their BBCP structure would reduce morphological changes after water submersion.…”

“…The direct synthesis of well-defined, densely grafted amphiphilic BBCPs carrying cationic functional groups is challenging due to selecting a solvent to keep both blocks soluble. An alternative method is the postpolymerization modification of precursor BCPs to yield polymers with the charged blocks; however, this process can lead to incomplete modification and lower side-chain density. − Although direct creation of BBCPs with a high density of charged constituents in the polymer chains is challenging, our recent publication reported the first successful methodology to synthesize well-defined BBCPs by a grafting-through approach, yielding a densely charged macromolecular brush . These amphiphilic BBCPs were hypothesized to be able to form phase-separated morphologies in thin films and that their BBCP structure would reduce morphological changes after water submersion.…”