Synthesis and Micellization of Bottlebrush Poloxamers

Abstract

Bottlebrush polymers are characterized by an expansive parameter space, including graft length and spacing along the backbone, and these features impact various structural and physical properties such as molecular diffusion and bulk viscosity. In this work, we report a synthetic strategy for making grafted block polymers with poly­(propylene oxide) and poly­(ethylene oxide) side chains, bottlebrush analogues of poloxamers. Combined anionic and sequential ring-opening metathesis polymerization yielded low dispersity polymers, at full conversion of the macromonomers, with control over graft length, graft end-groups, and overall molecular weight. A set of bottlebrush poloxamers (BBPs), with identical graft lengths and composition, was synthesized over a range of molecular weights. Dynamic light scattering and transmission electron microscopy were used to characterize micelle formation in aqueous buffer. The critical micelle concentration scales exponentially with overall molecular weight for both linear and bottlebrush poloxamers; however, the bottlebrush architecture shifts micelle formation to a much higher concentration at a comparable molecular weight. Consequently, BBPs can exist in solution as unimers at significantly higher molecular weights and concentrations than the linear analogues.

Effect of Bottlebrush Poloxamer Architecture on Binding to Liposomes

“…Fitting the decay curve to the biexponential model indicated that the sizes of the populations differ by a factor of 2, which is attributed to a coexistence of free chains ( R h,free chains = 3.9 ± 0.5 nm) and micelles ( R h,micelles = 8.0 ± 1.5 nm). Because bottlebrush molecules adopt extended conformations, micelles are expected to be roughly twice as large as free chains ( R h,micelle ∼ 2 R h,free chain ) …”

“…Based on the side-chain lengths and grafting density, we expect the BBPs are loose brushes, so the side chains are Gaussian coils while the backbone is extended . Prior work has shown that the core dimensions of BBP micelles reflect the behavior of a wormlike chain with a persistence length of ∼10 nm, which is significantly higher than the 0.7 nm persistence length of linear polynorbornene …”

“…Autocorrelation functions were recorded for 4 min, at angles of 60, 75, 90, 105, and 120° over a delay time range of 1 μs to 100 ms. The data were then fit to the second-order cumulant expansion model and the biexponential model, and in all cases, the second-order cumulant expansion model yielded equally random residuals with fewer fitting parameters, indicating a superior fit and therefore a single relaxation mode …”

“…Note that in the case of PPO, a hydrogenation reaction was performed prior to the condensation reaction to eliminate alkene α-chain-end impurities . Percent norbornene functionality was assessed via matrix-assisted laser desorption/ionization time of flight (MALDI-ToF) spectrometry and 1 H NMR spectroscopy and was found to be quantitative for PPO-1k, 94% for PEO-2k, and 92% for PEO-0.6k (Figure S1). PEO-2k was purified via two precipitations in cold diethyl ether, and PPO-1k and PEO-0.6k were purified by vacuum drying at 40 °C for 7 days.…”

“…For example, the segmental relaxation time (chain mobility) is a function of side-chain length. − Longer side chains decrease steric constraints at the units far from the backbone, which enhances interdigitation between chains . Therefore, by combining an efficient strategy to synthesize bottlebrush polymers with PEO and PPO side chainsdenoted bottlebrush poloxamers (BBPs)with knowledge of parameter–property relationships, the bottlebrush architecture can be used as a tool to inform the stabilization mechanism(s) of block polymers.…”