Polymer Chemistry Blog

Zhang and co-workers report aqueous polymerization-induced self-assembly by atom transfer radical polymerization to generate protein-based nanoassemblies.

Polymerization-induced self-assembly (PISA) has opened the way for the in-situ formation of a wide range of nanoparticles with applications ranging from the material to the biomedical field. However, the vast majority of reports focus on utilizing reversible addition-fragmentation chain transfer polymerization as the main methodology while atom transfer radical polymerization (ATRP) is very rarely combined with PISA, mostly due to the limitations of ATRP in water. Zhang and co-workers utilized Cu(0) reversible deactivation radical polymerization by exploiting the disproportionation of CuBr/ligand in aqueous media generating both Cu(0) particles and Cu(II) deactivator. Upon modifying Candida Antarctica lipase B (CALB), it was used as a macroinitiator for both hydrophilic and hydrophobic monomers generating well-defined protein-based nanoassemblies. A range of acrylamide and acrylate based monomers were successfully polymerized under mild reaction conditions (e.g. room temperature) via he “grafting from” strategy. When hydrophilic monomers were selected, water-soluble conjugates could be obtained in a facile manner while by polymerizing more hydrophobic monomers yields spherical nanoparticles, consistent to a traditional PISA formulation. Importantly, it was also found that they hydrolysis of the ester bonds can be very significant in the presence of lipase-based macroinitiators, which will catalyze the hydrolysis of poly(acrylate) to poly(acrylic acid). The versatility of the reported methodology combined with the use of mild reaction conditions may find applications in enzyme immobilization and nanoreactors.

Tips/comments directly from the authors:

1. It is necessary to purify the commercial CuBr as it could be partially oxidized during storage and routine use.
2. Typical Cu(0)-RDRP in water is fast enough to reach full conversion in minutes; however, the polymerizations would be slower when grafting from proteins, possibly due to the low concentration of macroinitiators.
3. Although copper ions were known to be able to denature proteins, CALB still maintained its function after polymerization. The mild reaction conditions such as aqueous system, low reaction temperature (0-25 ℃) and fast polymerization rate (minutes to hours) could be suitable for more sensitive proteins.
4. The degradation of lipase-poly(acrylate) conjugates was fast and gradual disappearance of precipitates could even be visually observed during the dialysis in water. So it is better to quickly purify the conjugates via centrifugation. From another point of view, such conjugates could be potentially used for drug delivery and controlled release.

Citation to the paper: Synthesis of lipase–polymer conjugates by Cu(0)-mediated reversible deactivation radical polymerization: polymerization vs. degradation, Polym. Chem., 2020, 11, 1386-1392, DOI: 10.1039/c9py01462d

Link to the paper:

https://pubs.rsc.org/en/content/articlelanding/2020/py/c9py01462d#!divAbstract

This paper is free to read until 10th April 2020!

About the Web Writer

Dr. Athina Anastasaki is an Editorial Board Member and a Web Writer for Polymer Chemistry. Since January 2019, she joined the Materials Department of ETH Zurich as an Assistant Professor to establish her independent research group.

Zhang and Gutekunst utilize functional enyne molecules in pulsed-addition ring-opening metathesis polymerization to generate multiple functional polymer chains from a single 3^rd generation Grubbs initiator.

Ring-opening metathesis polymerization (ROMP) has gained popularity within the polymer chemistry community thanks to the invention of functional group-tolerant ruthenium-based initiators. However, remaining challenges in the area include the use of stoichiometric amounts of metal and the difficulty to satisfactory control the end-group functionality. To address these challenges, Gutekunst and Zhang have elegantly employed functional enyne molecules in pulsed-addition ring-opening metathesis polymerization. This led to the generation of multiple functional polymer chains from a single 3rd generation Grubbs initiator. Importantly, all polymers synthesized displayed monomodal molecular weight distributions and very low dispersity values, as characterized by size exclusion chromatography, thus supporting the high efficiency of enyne chain-transfer. Detailed analysis of the molecular weights obtained from each pulse demonstrate that 50% of the ruthenium initiator remains active even after 10 cycles which corresponds to 4% of catalyst death per cycle. This is improved over previous established protocols where 8.5% of catalyst death per cycle was reported. The materials synthesized were further characterized by mass-spectrometry. In particular, matrix assisted laser desorption ionization showed extremely high end-group fidelity obtained using the enyne chemistry with a single polymer distribution and no observable side reactions. Different monomer structures were tested, the vast majority of which were compatible with the developed protocol. Bifunctional enyne molecules can also be used to give heterotelechelic polymers. Last but not least, the possibility of diblock copolymer formation was also examined yielding well-defined block copolymers with low final dispersity values. It is the author’s belief that their user-friendly and catalyst economical method will yield to the facile synthesis of materials with reduced metal contamination thus paving the way for further biomedical and electronic applications.

Tips/comments directly from the authors:

1. An inert atmosphere is important to this protocol, though a glovebox is not needed. All experiments were performed with a standard Schlenk line, and solutions were degassed by simply bubbling with nitrogen gas.
2. Three equivalents of the enyne CTA are used to ensure complete conversion of the Grubbs 3rd generation initiator, but only 1.2 eq is needed for full transfer after a given polymerization cycle of an exo-norbornene imide monomer. This reflects the differences in reactivity between ruthenium alkylidenes and benzylidenes with the enyne CTAs.
3. The exo-Oxanorbornene imide examined in this protocol was also effective but required 2.4 eq of the enyne CTA to recycle the system. This implies that different monomers may have variable reactivities. 1H NMR is very useful to monitor this process, as each of the ruthenium alkylidene/benzylidene species have diagnostic chemical shifts.
4. Small molecule byproducts are formed in each cycle but are inert under the reaction conditions and do not interfere with the polymerization.
5. If any readers are interested in using this approach, feel free to reach out to willgute@gatech.edu with any questions.

Citation to the paper: Pulsed-addition ring-opening metathesis polymerization with functional enyne reagents, Polym. Chem., 2020, 11, 259-264, DOI: 10.1039/c9py00965e

Link to the paper:
https://pubs.rsc.org/en/content/articlepdf/2020/py/c9py00965e

The use of a polymethylmethacrylate (PMMA) containing an unsaturated chain end as a macroinitiator during reversible complexation mediated polymerization has been previously reported by Goto and coworkers. Typically, such macroinitiators can also be used as macromonomers to generate branched polymers via propagation. In this work, Goto and co-workers elegantly demonstrate that the occurrence of addition-fragmentation chain transfer and propagation strongly depends on the temperature during the polymerization of styrene. Through carefully monitoring the kinetics of the polymerization of styrene, the authors discovered that propagation is predominant below 60 ̊C, consistent with previous reports. However, upon elevating the temperature (e.g. 120 ̊C), addition-fragmentation chain transfer dominates instead. This discovery then allowed access to the efficient synthesis of block copolymers with PMMA and polystyrene at high temperatures. Importantly, addition-fragmentation chain transfer was also predominant over propagation during the polymerizations of acrylonitrile and acrylates yielding well-defined block copolymers. PMMAs with different molecular weights were also investigated and the polymerization was controlled utilizing iodine transfer polymerization for styrene and reversible complexation mediated polymerization for the other monomers. Such an approach is highly advantageous due to the ease of the operation and it is expected to be a practical alternative for efficient block copolymer synthesis.

Tips/comments directly from the authors:

1. The proper purification of polymers and the careful NMR analysis were important for obtaining the accurate kinetic data. The kinetic study provided a useful idea enabling the synthesis of block copolymers of PMMA with polystyrene (PSt).
2. Block copolymers of PMMA with PSt, polyacrylonitrile, and polyacrylates are accessible. Relatively high monomer conversions are achievable.
3. Not only the isolated alkyl iodide but also the alkyl iodide in situ generated from iodine (I₂) and azo compound can effectively be used as the initiating dormant species. The in situ method is less expensive and robust and hence can be a practically attractive

Read the full article now for FREE until 10th January!

Synthesis of block copolymers using poly(methyl methacrylate) with unsaturated chain end through kinetic studies, Polym. Chem., 2019, 10, 5617-5625, DOI: 10.1039/c9py01367a

About the web writer

Dr. Athina Anastasaki is an Editorial Board Member and a Web Writer for Polymer Chemistry. Since January 2019, she joined the Materials Department of ETH Zurich as an Assistant Professor to establish her independent research group.