Facile Synthesis of Worm-like Micelles by Visible Light Mediated Dispersion Polymerization Using Photoredox Catalyst

The overall goal of this protocol is to demonstrate the Facile Synthesis of Worm-like Micelles using Visible Light Mediated Polymerization. This method involves the preparation of polymerate nanoparticles, which can be used for a range of applications such as nano medicine The main advantage of this procedure is the production of worm-like nanoparticles using two-step procedure. The implication of this technique extends towards the field of drug delivery because in a number of studies, drug loaded worm-like nanoparticles have shown to give increased cellular uptake.

To begin this procedure, add the appropriate reagents as indicated in the text protocol, a magnetic stir bar and 50 milliliters of acetone nitrile to 100 milliliter round bottom flask. Seal the flask with an appropriately sized rubber septum and steel wire. Then, cool the flask to less than four degrees Celsius in an ice water bath.

Following this, de-oxygenate the flask for thirty minutes by bubbling nitrogen directly into the reaction mixture through a 21 gauge needle with a second 21 gauge needle acting as a vent. Place the flask in an oil bath at 70 degrees Celsius for five and a half hours. Once the reaction is complete, quench the polymerization by immersing the flask directly in an ice water bath and exposing the contents to air.

Next, remove the acetone nitrile by agitation under a continuous stream of compressed air. Then, redissolve the crude mixture in approximately 40 milliliters of tetrahydrofuran or THF. Now, add the contents of the flask dropwise to 400 milliliters of a rapidly stirred mixture of petroleum spirits and diethyl ether and continue to stir until the supernatant is no longer cloudy.

Once the precipitation is complete, decant the supernatant and redissolve the polymer residue in approximately 40 milliliters of THF. Repeat the precipitation process at least two more times to ensure complete removal of the residual monomer. Then, remove the excess solvent from the purified homopolymer by agitation under a continuous stream of compressed air, followed by drying in a vacuum oven for four hours.

At this point, determine the number average molecular weight of the homopolymer by nuclear magnetic resonance spectroscopy, using a previously reported method. Using gel permeation chromotography, calculate the polymer dispersity. If the molecular weight of your synthesized homopolymer deviates from the 9000 molecular weight presented here, it may still be possible to obtain a worm gel in the subsequent step.

However, the reaction time will vary. At this point, prepare a one milligram per milliliter stock solution of the ruthenium based photo redux catalyst in ethanol. Store the stock solution in a refrigerator to minimize solvent evaporation.

Next, plug a pasteur pipette with a small wad of cotton wool using a second pipette to help pack it tightly. Pour basic aluminum oxide into the pipette to give a height of approximately five centimeters. Then, remove the mono methyl ether hydroquinone inhibitor in BzMA by passing approximately three milliliters through the pipette and collecting the de-inhibited BzMA.

Add the de-inhibited BzMA, the homopolymer, the ruthenium catalyst stock solution, acetone nitrile, ethanol, and magnetic stir bar, to a four milliliter glass vile. Then, perform the deoxygenation procedure as previously described. Following this, place the vile in a 2000 milliliter glass beaker lined with blue LED strips and irradiate at room temperature with magnetic stirring.

After twenty hours, monitor the reaction vile routinely and remove it from the reactor when the high viscosity solution forms a freestanding gel when the vile is inverted. So if your reactor setup is different to that presented here, gelation which indicates the formation of worm-like micelles will still be observed, however at a different reaction time. And that will really depend on the rate of polymerization of your reactor.

After removing the vile from the reactor, quench the polymerization by exposing the nanoparticle gel to air for a few minutes. Store the closed vial upright in the dark. For TEM imaging place approximately 40 milligrams of the crude nanoparticle gel in a four milliliter glass vial.

Continuously agitate the nanoparticle gel using a vortex mixer and add four milliliters of ethanol dropwise over a period of at least five minutes. Remove any macroscopic aggregates from the diluted nanoparticle sample by filtering through glass wool. Finally, perform TEM imaging of the diluted nanoparticle sample according to a previously reported procedure.

In this study a two step polymerization protocol is used for the synthesis of worm-like micelles using a PISA approach. During the polymerization the initially transparent reaction mixture becomes cloudy in accordance with the dispersion polymerization and eventually transitions to a highly viscous gel like state indicating the formation of worm-like micelles. Indications of a living polymerization are apparent with low polymer dispersities and a good correlation between the molecular weight and momomer conversion.

In addition, gel permeation chromatography traces indicate a predominately unimodal distribution with varying conversion, although some high molecular termination and low molecular weight tailing is observed in this system. The formation of the worm-like micelle morphology is also achievable under different reaction conditions such as variable vial types and reagent compositions but also if the light source is applied in an intermittent fashion. This implies that despite the strong effect of light penetration on polymerization rates in most photopolymerization systems the gelation behavior in this protocol can still be used as a reliable indicator for worm-like micelle formation.

After watching this video, you should have a good understanding of how to generate nanoparticles with programmable shape that are capable of self organizing into gel.