Particles without a Box: Brush-first Synthesis of Photodegradable PEG Star Polymers under Ambient Conditions

Poly(ethylene glycol) (PEG) brush-arm star polymers (BASPs) with narrow mass distributions and tunable nanoscopic sizes are synthesized in via ring opening metathesis polymerization (ROMP) of a PEG-norbornene macromonomer followed by transfer of portions of the resulting living brush initiator to vials containing varied amounts of a rigid, photo-cleavable bis-norbornene crosslinker.

The overall goal of the following experiment is to learn how to make a series of polyethylene glycol or PEG based nanoparticles in parallel using ring opening metathesis, polymerization, or rom. This goal is achieved by first synthesizing a suitable macro monomer and crosslinker. These compounds define the final nanoparticle properties in the second step.

The macro monomer is polymerized by romp to yield a batch of living bottle brush polymers with peg side chains. Next, the living bottle brush polymers are transferred to vials with different amounts of crosslinker in order to initiate nanoparticle growth. This procedure can yield a diverse range of nanoparticles with molar masses that depend on the amount of crosslinker added and functionality that is defined by the macro monomer and crosslinker structure.

The molar masses can then be determined by gel permeation chromatography. The main advantage of this technique over existing methods like free radical polymerization, is that it can be performed very quickly on the benchtop and can be used to polymerize a wide range of monomers that are densely functionalized and cly. Demanding Visual demonstration of this method is critical because though it is simple, it requires a significant amount of multitasking.

Demonstrating this procedure today will be Jenny Lu, a graduate student from my group. First, add 300 milligrams of monoamine terminated polyethylene glycol 3000 or peg amine 3000 to a 40 milliliter scintillation vial, equipped with a stir bar. Following this, add three milliliters of anhydrous dimethylformamide or DMF to the vial to dissolve the peg amine.

Allow the solution to stir and heat lightly until all the peg amine has dissolved. After adding 36 milligrams of Norbertine NHS Ester, cap the vial and stir the reaction mixture at room temperature overnight. When finished, remove the stir bar and add roughly 35 milliliters of cold ethyl ether to the reaction solution.

To precipitate the peg macro monomer, filter the white fluffy precipitate using a buchner funnel and wash it extensively with dathyl ether. Then transfer the precipitate to a 20 milliliter scintillation vial and dry under vacuum for 24 hours. To remove residual dathyl ether to prepare catalyst A, add 500 milligrams of grubs, second generation catalyst to a 20 milliliter scintillation vial.

Equipped with a stir bar, add approximately 0.5 milliliters pur into the vial, and observe the solution. Color change from red to green. Allow the reaction disturb briefly until all of the red color has disappeared and the solution has become viscous.

If the red color has not completely disappeared, add more purine as needed. Following this, fill the reaction vial with approximately 20 milliliters of cold pentane to precipitate complex A.If needed, use a spatula to breakup the precipitate. Filter the suspension using a buer funnel to collect the green precipitate.

Then wash the precipitate with four times 15 milliliters of cold pentane. Transfer the green solid to a 20 milliliter scintillation vial and dry it under vacuum overnight. In a three milliliter vial, equipped with a stir bar, carefully weigh out 65 milligrams of peg macro monomer.

B.If necessary, use a static gun to remove static from the vials and spatula. After adding 158 microliters of tetra hydro FU or THF to the vial, immediately cap it to prevent solv evaporation. Allow the solution to stir and heat lightly if necessary, until all of the macro monomer is dissolved to a three milliliter vial containing 2.8 milligrams of catalyst A at 466 microliters of anhydrous hydro furin to give a six milligram per milliliter catalyst solution.

Once the vial has been capped, gently swirl it so the catalyst completely dissolves, yielding a forest green colored solution. After transferring the catalyst solution to a syringe, place the needle tip just above the stirring macro monomer mixture and quickly add 243 microliters of the solution to the vial. Cap the vial immediately and allow the reaction mixture to stir for 15 minutes to form the living brush initiator.

A living brush initiator should be used immediately for step five. Next carefully, add 3.6 milligrams, 5.5 milligrams, and 7.3 milligrams of a previously prepared biz norbertine NBO crosslinker to three separate, three milliliter vials equipped with stir bars. Alternatively, the crosslinker can be added to these vials prior to beginning.

Step four, above. Transfer the living brush initiator solution to a syringe. Place the needle tip just above the solid crosslinker and add 123 microliters of the solution to each of the three vials.

Immediately cap the vials and turn on the stir plate. Stir the three brush arm star polymer or BSP formation Reactions at room temperature until completion. BA formation with this specific macro monomer and crosslinker is complete in four hours.

However, the reactions can be left for up to 24 hours without consequence. Quench the reactions by adding one drop of ethyl vinyl ether. Stir for 10 minutes to ensure complete quenching following dilution filtration.

Analyze the samples by GPC. In this study, PEG macro monomers B one, B two, and B three were prepared from different PEG immune sources and the BA nanoparticle formation results before and after rigorous prepared of high performance liquid chromatography. Macro monomer purification were compared, shown here are GPC traces for a variety of bass prepared from B one, B two and B three.

In all cases, the data illustrate that increasing the equivalence of crosslinker leads to an increase in the molar mass of the bass. As was observed previously, 10 equivalence of crosslinker is not sufficient to achieve uniform bps. The sample shows a clearly multimodal GPC trace with a large amount of residual brush polymer, especially in the case of un purified macro monomer.

B one, greater amounts of crosslinker result in uniform molar mass distributions with very little residual brush. In macro monomer, the weight average molar mass approximately doubles and going from 15 to 20 equivalent in the case of B three, no residual macro monomer and less than 1%residual brush remains for the 15 and 20 equivalent cases Once mastered, this technique can be used to make libraries of many more than three particles and parallel if it is performed properly. While attempting this procedure, it's important to remember to keep track of each vial and the proper amounts of reagents to add to each vial, especially as the library size increases.

Good record keeping and attention to detail is critical. Following this procedure, you can make materials for a range of different applications that include drug delivery, self-assembly, and supported catalysis simply by changing the different macro monomers and cross linkers, or by using mixtures of macro monomers and cross linkers.