Polymer Chemistry Blog

Constantinou & Georgiou report the synthesis of thermoresponsive triblock copolymers using group transfer polymerisation.

Thermoresponsive polymers can find use in a wide range of applications including tissue engineering and 3-D printing. For the successful synthesis of thermoresponsive gels several criteria need to be taken into account such as the composition, the molar mass, the concentration and the architecture. Georgiou’s group elegantly demonstrate the facile synthesis of such materials through group transfer polymerisation (GTP) thanks to its unique characteristics including scalability and faster reaction rates in comparison to conventional radical polymerisations. Different copolymers were targeted based on the ionic hydrophilic pH and thermoresponsive 2-(dimethylamino)ethyl methacrylate (DMAEMA), the non-ionic poly(ethylene glycol) (PEG)-based methacrylate (methoxy di-, penta-, and nona(ethylene glycol) methacrylate, DEGMA, PEGMA, and NEGMA), and the hydrophobic BuMA. The effect of the PEG side chain length and different compositions were systematically varied in order to investigate their effects on the thermoresponsive behaviour of the copolymers. Micelle formation was observed for all the terpolymers and the effective pK_as were affected by the hydrophobic BuMA content and the architecture. Interestingly, the cloud points were affected by both the composition (BuMA content) and the PEG side group length and increase as the hydrophilic content and the PEG length increased. The gel points were investigated over a wide range of temperatures and concentrations and found to be influenced by both the composition and the PEG side chain length. Stable gels were formed by the most hydrophobic and with the shortest PEG length macromonomers. In summary, it was demonstrated that the sol–gel transition can be tailored by varying both the PEG length as well as the composition of the polymers.

Tips/comments directly from the authors:

1. It is really important to monitor the temperature between additions during the one-pot synthesis. GTP is exothermic so when all monomer has converted to the polymer the temperature will drop back down so the next monomer can be added.
2. Since each addition/polymerisation step takes about 10-15 the reaction can be monitored in real time by gel permeation chromatography, if necessary.
3. Even though ideally all monomers have to be distilled this is not necessary when the GTP reaction is scaled up as long as the monomers are dry.
4. Gelation is also influenced by ionic strength so if salt is added to the polymer solutions the solution will gel at lower temperatures and concentrations.

Thermoresponsive gels based on ABC triblock copolymers: effect of the length of the PEG side group by A. P. Constantinou and T. K. Georgiou , Polym. Chem., 2016, 7, 2045-2056

Dr. Athina Anastasaki is a Web Writer for Polymer Chemistry. She is currently an Elings fellow working alongside Professor Craig Hawker at the University of California, Santa Barbara (UCSB). Please visit  her webpage for more information.

Bilalis et al. report the design and synthesis of novel pH-sensitive nanogates based on poly(L-histidine) from mesoporous silica nanoparticles.

The development of novel drug delivery materials necessitates the combination of the knowledge from different scientific fields, including organic and inorganic chemistry. Among the wide range of hybrid organic/inorganic materials, mesoporous silica nanoparticles (MSNs) have attracted considerable attention thanks to their unique characteristics such as high surface area, large specific volume, controllable pore diameter, facile surface functionalization and nontoxicity. On the other hand, polypeptide-coated silica-based systems, including poly(L-histidine) (PHis), have shown great promise in preventing untimely release of drugs and as such the combination of PHis and MSNs can provide an excellent template for the design of advanced drug delivery systems for controlled release applications. To this end, Iatrou, Bilalis and co-workers have exploited surface-initiated ring-opening polymerization (ROP) to synthesize novel pH-sensitive poly(L-histidine)-grafted mesoporous silica nanoparticles through an amino-functionalized MSN intermediate. The successful grafting of the homopolypeptide chains from the surface of MSNs was demonstrated by Fourier Transform-infrared spectroscopy (FT-IR), transmission electron microscopy (TEM) and thermogravimetric analysis (TGA) while size exclusion chromatography (SEC) confirmed the controlled character of the polymerization. Dynamic light scattering (DLS) and zeta potential analysis were also employed to ascertain the pH-responsive nature of the polypeptide-gated MSNs. In addition, drug loading and release studies were performed in order to verify the role of the grafted PHis chains as pH-sensitive nanogates for the MSN pores utilizing the model anticancer drug doxorubicin (DOX). DOX was efficiently loaded within the nanochannels of the hybrid MSN@PHis (~90%) and the drug entrapment and release pattern were proved to be pH-dependent with exert stability at physiological pH. The combination of the positive characteristics of MSNs and poly(L-histidine) enables the described materials as promising drug nanocarriers with potential in vitro and in vivo applications.

Tips/comments directly from the authors:

1. It is really important to strictly maintain the reported time of reaction during the synthesis of MSNs using TEOS. Longer or less time of reaction will lead to larger or smaller nanoparticles, respectively.
2. It should be noted that the functionalization of the surface of MSNs with APTES was conducted before the removal of CTAB so as to avoid the grafting of PHis chains from the MSN nanopores.
3. When following the reported functionalization procedure, a LiOH solution must be used in order to remove HCl traces from the amino groups of MSNs after the removal of CTAB.
4. The loading procedure of DOX into the MSN nanopores should take place at acidic pH (3.0). In that way the maximum drug encapsulation is ensured, because the PHis nanogates are in an opened state (fully protonated and thus hydrophilic).

pH-Sensitive nanogates based on poly(L-histidine) for controlled drug release from mesoporous silica nanoparticles by P. Bilalis, L.-A. Tziveleka, S. Varlas and H. Iatrou, Polym. Chem., 2016, 7, 1475-1485, DOI: 10.1039/C5PY01841B

Dr. Athina Anastasaki is a Web Writer for Polymer Chemistry. She is currently an Elings fellow working alongside Professor Craig Hawker at the University of California, Santa Barbara (UCSB). Please, visit her webpage for more information.

Zhang et. al. report a significant photoenhancement effect on classical ATRP and ATRP derivatives by ambient laboratory light.

Since the introduction of atom transfer radical polymerisation (ATRP) by Matyjaszewski and Sawamoto, a large diversity of other copper adjuncts have attracted considerable interest including activator regenerated by electron transfer (ARGET)-ATRP, activator generated by electron transfer (AGET)-ATRP, initiators for continuous activator regeneration (ICAR)-ATRP and single electron transfer living radical polymerisation (SET-LRP). Recently photoinduced copper radical polymerization has also drawn significant attention as CuBr₂, typically referred to as deactivating species, can be reduced in situ generating the active CuBr species in the presence of UV or visible light. In this contribution, Jordan and co-workers investigated on whether the typical laboratory light would have any considerable impact on standard ATRP reactions. Interestingly, the vast majority of the ATRP techniques (with the exception of ARGET-ATRP) demonstrated a remarkable photoenhancement effect by ambient light, originated from common fluorescent lamps. It was observed that when less copper complex is utilized for the polymerizations, a stronger influence of the ambient light in the monomer conversion is evident and this effect was significant even in the presence of additional reducing agents. As a general rule, it was concluded that the slower the polymerization is, the more pronounced the effect of the ambient laboratory light can be. As it was proved that it makes a difference if one is performing an ATRP reaction with the hoods on and off, the effect of the laboratory light on the polymerization can no longer be neglected and the authors encourage the report of the light conditions in typical ATRP experiments in order to ensure the reproducibility. 

Tips/comments directly from the authors:

Comments:
In this study, we provide conclusive evidence that common laboratory light especially originating from fluorescence lamps has a significant impact on ATRP. This is most probably one main reason why reproducibility of ATRP reactions are not as it should be which impairs further development of controlled radical polymerization techniques. As shown, the impact of light is different for the different ATRP recipes and will also strongly vary with the:

1. Type of complex formed regarding the metal and the ligands;
2. Quantity/concentration of metal complex formed and surely;
3. Type of illumination (natural light, type of fluorescent lamps installed in the laboratory and light intensity in the reaction vial). Strong influence were found for the “hood light illumination” (see Fig. 1 for description and Fig. 2 for experimental data) which was also very surprising for us. We therefore suggest to check the type of light bulbs/source of light, consider their emission spectra and resulting intensity at the location of the reaction and possibly provide these details in the experimental section to ensure reproducibility.

Tips:
1. The various metal complexes used in ATRP are most probably photosensitive but to a different extent. Thus, the influence of laboratory light will vary.
2. Perform the ATRP reactions always under the same light settings with the same light source and provide details (type of lamp, light intensity at each location of the reaction) in the experimental section.
3. Especially modern fluorescent lamps have a higher emission in the blue range and thus may have a stronger/other influence upon conversion/kinetics of the ATRP. Check the emission spectra of the lamps installed in the laboratory and especially in the chemical fume hoods.

Lights on! A significant photoenhancement effect on ATRP by ambient laboratory light by Tao Zhang Dan Gieseler and Rainer Jordan, Polym. Chem., 2016, 7, 775-779

Dr. Athina Anastasaki is a Web Writer for Polymer Chemistry. She is currently an Elings Fellow working alongside Professor Craig Hawker at the University of California, Santa Barbara (UCSB).Visit her webpage for more information.