Direct Fluorination of Poly(3-hydroxybutyrate-co) - American Chemical

Chapter 20

Downloaded by MONASH UNIV on September 20, 2015 | http://pubs.acs.org Publication Date (Web): November 22, 2013 | doi: 10.1021/bk-2013-1144.ch020

Direct Fluorination of Poly(3-hydroxybutyrate-co)-hydroxyhexanoate Samsuddin F. Mahmood, Benjamin R. Lund, Sriram Yagneswaran, Shant Aghyarian, and Dennis W. Smith, Jr.* Department of Chemistry and the Alan G. MacDiarmid NanoTech Institute, The University of Texas at Dallas, Richardson, Texas 75080, U.S.A. *E-mail: [email protected]

Polyhydroxyalkanoates (PHAs) are a class of polymers synthesized by bacteria as intracellular carbon and energy storage granules. PHAs are biodegradable with tailorable physical properties; however, often their properties are not ideal for many applications. The incorporation of fluorine containing substituents within these polymers or direct surface modification to enhance the fluorine content of these polymers, and thus their surface properties, should greatly enhance their utility and speed their adoption for a range of applications. Direct fluorination of poly(3-hydroxybutyrate-co)-hydroxyhexanoate (hereafter P3HB-co-HH) was carried out at elevated pressure with elemental F2/N2 gas mixture. Fluorination of P3HB-co-HH showed marked changes in both thermal and chemical characteristics. Fluorination was demonstrated by X-Ray Photoelectron Spectroscopy (XPS), Attenuated Total Reflectance – Fourier Transform Infrared Spectroscopy (ATR-FTIR), and Nuclear Magnetic Resonance Spectroscopy (19F NMR). The effect of fluorination on the physical properties of F-P3HB-co-HH was probed by Gel Permeation Chromatography (GPC), Thermo Gravimetric Analysis (TGA) and Differential Scanning Calorimetry (DSC).

© 2013 American Chemical Society In Green Polymer Chemistry: Biocatalysis and Materials II; Cheng, H., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 2013.


Introduction and Background Interest in biorenewable polymers among the scientific and industrial communities has grown substantially in recent years. Production from biorenewable feedstocks, degradation into biofriendly components, and (often) compatibility within the human body have made biorenewable polymers an excellent alternative to traditional petroleum based polymeric materials for specific applications. Among these, aliphatic polyesters (poly(lactic acid) PLA and poly(hydroxyalkanoates) PHA) have gained preeminence due to their facile synthesis and good physical properties (Figure 1) (1, 2). By far, the greatest share of academic and industrial research has targeted PLA, however, PHAs are making inroads due to their unique plastic like properties (similar to polypropylene in some cases) and degradation under both aerobic and anaerobic conditions.

Figure 1. General structures for poly(hydroxy alkanoate) (PHA) and poly(lactic acid) (PLA).

Traditionally, synthesis of PLA polymers has been achieved by oligomerization of lactic acid, cyclization to lactide, and polymerization to high molecular weight polymers via ring opening polymerization with a tin catalyst (3). Lactide exists in two isomeric forms (D and L) can be polymerized as homo- or copolymers comprising various ratios of the two stereoisomers (Figure 2). Controlling monomer feed ratios allows for control over the properties of the resultant material in terms of crystallinity, thermal stability, rate of degradation, etc. (4). Additionally, blends of PLA with other polymers as well as copolymerization with other monomers (caprolactone for example) have worked to further expand the breadth of physical properties of known PLA polymers. PLAs have been explored for a range of applications, with special interest paid by biomedical device community, due to its low cost and biocompatibility (5). In biological environments PLA degrades back to its monomeric form, lactic acid, which is a natural byproduct of the human body. This degradation is generally slow (being effected by surface area and crystallinity of the sample) and non-toxic due to the low amounts of biomimetic waste formed. Many PLA based devices have been approved by the FDA for applications ranging from bone plates to drug eluting stents (6).

292 In Green Polymer Chemistry: Biocatalysis and Materials II; Cheng, H., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 2013.


Figure 2. Ring opening polymerization (ROP) of lactide (L or D). Homopolymers of L and D lactide form PLLA and PLDA as well as random copolymer of L and D lactide to form D,L-PLA or racemic PLA if molar ration of L to D is 50:50.

PHA polymers are synthesized by an entirely different route from PLA polymers. Bacteria form PHA macromolecules as intracellular carbon and energy storage granules (7). These bacteria can be encouraged to synthesize PHA polymers in bioreactors by culturing them, allowing them to grow, stimulating them to produce PHA polymers (via changing the environment of the culture, decreasing nutrient levels, lowering oxygen levels, changing trace element concentrations, etc.) and then harvesting the PHA polymers from the bacteria (via centrifugation, extraction, and precipitation) (Figure 3). The resultant properties of the PHA polymer can be tailored by the feedstock (monomer) given to the bacteria (8).

Figure 3. General lifecycle of PHA synthesis and development. 293 In Green Polymer Chemistry: Biocatalysis and Materials II; Cheng, H., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 2013.


Fluorine Containing PLAs and PHAs Fluoropolymers possess many desirable properties such as excellent thermal stability, chemical inertia, solvent resistance, excellent barrier properties, low coefficient of friction and low surface energy, to name a few (9). Many of these properties are of particular interest to applications where surface interactions are important such as paints, adhesives, biomaterials, coatings, etc. Fluoropolymers, however are often difficult to process, lacking solubility in many common solvents, and phase separate when blended with many engineering thermoplastics. Alternative techniques including the formation of block copolymers, end capping and surface functionalization through physical and chemical means have been employed to enable the interaction of fluorinated and non-fluorinated materials. PLAs and PHAs possess many useful qualities, as previously discussed; however, their physical properties are not ideal for many applications. The incorporation of fluorine containing substituents within these polymers or direct surface modification to enhance the fluorine content of these polymers, and thus their surface properties, should greatly enhance their utility and speed their adoption for a range of applications. One such application, explored by Lee et al, was the controlled functionalization of a fluorine endcapped poly(lactide-co-glycolide) surface by plasma treatment (10). Due to the favorable interactions of fluorine at the air polymer interface the fluorocarbon segments bloomed to the surface, displacing proximal hydrophilic hydroxyl functionalities. Subsequent plasma treatment was utilized to predictably control the hydroxyl functionalization of the fluorocarbon surface for anchoring of a range of biomolecules. Endcapping of the poly(lactide-co-glycolide) polymers was achieved utilizing a hydroxyl terminated fluorocarbon (Figure 4). This approach produced polymers with molecular weights (Mn) varying from 14 KDa to 74.3 KDa (PDI ~2) and Tgs ranging between 35 and 53 °C with Tms between 156 and 174 °C. Alternately, work on diblock copolymers of poly(lactic acid-coperfluoropropylene oxide) (PLA-FPO) was used to explore the formation of micelles in supercritical CO2 (11). Fluoropolymers exhibit excellent solubility in supercritical CO2 whereas PLA does not. The formation of amphiphilic PLA-FPO copolymers allowed for the preferential segregation of these polymers into micelles in supercritical CO2. The formation of fluorocarbon enchained triblock copolymers with PLA was initially performed to enhance the processability of caprolactone triblock copolymers with enchained Fomblin™ Z-DOL TX (12). Due to the selective chiral nature of PLA (L, D, or rac) the incorporation of PLA was utilized to decrease the crystallinity of the caprolactone triblock copolymer and enhance the processability of the system. The PLA copolymers exhibited glass transitions (Tg) ranging from -60 to 15 °C with increasing PLA content and melting temperatures from 35 to 47 °C with increasing caprolactone content. In a similar fashion, our group explored the formation of segmented copolymers with PLA and fluorocarbon segments. Specifically, triblock copolymers of PLA-Fomblin-PLA were formed with a range of fluorine loading levels (1-20 wt%) (13). It was found that the optimum loading of fluorine 294 In Green Polymer Chemistry: Biocatalysis and Materials II; Cheng, H., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 2013.


occurred at 5 wt% whereas higher fluorine loading levels produced little change in the polymer’s properties. Further work done by our group explored the scalability of these systems to understand their potential for industrial applications (14). It was found that batches on the liter scale were attainable with excellent reproducibility. Specific applications of this system have been researched for historical preservation applications (15, 16).

Figure 4. PLA endcapped and enchained fluoropolymers. (A) Fluorocarbon endcapped poly(lactide-co-glycolide). (B) Segmented triblock copolymer with Fomblin Z-DOL TX core and flanking random poly(caprolactone/D,L-lactide) copolymer segments. (C) Segmented triblock copolymers with Fomblin Z-DOL core and flanking PLLA homopolymer segments.

Alternately, early work on fluorinated PHA polymers was achieved through microbe synthesis, feeding pseudomonas putida fluorophenoxy alkanoic acids and stimulating the bacteria grown the fluorinated PHA polymer (Figure 5). Molecular weights (Mn) of ~10,000 Da were achieved with reasonable polydispersities (PDI ~2-3) (8). Uniquely, melting temperatures of >100 °C were attained for these fluoro PHA polymers. More recent work on poly(3-hydroxybutyric acid-co-3-hydroxyvaleric acid) (PHBV) utilized plasma polymerization to form fluoropolymer films on the surface of PHA polymers to enhance barrier properties and retard degradation. Plasma fluorination was achieved by utilizing a plasma source (14.56 Hz rf generator) and a fluorocarbon feedstock. The fluorocarbon was introduced to the plasma where it began to dimerize, oligomerize and polymerize in the gas phase. The reactive fluorocarbon material condensed onto the PHA surface, reacting with it and each other to form a dense, often crosslinked, fluoropolymer layer on top of the PHA. The process enhanced the contact angle of the PHA polymers from 74° to 98° and dramatically extended its degradation from 5 days to 8-14 days (depending on fluorination conditions) (17). Indeed, this technique has been extended to PLA polymers where it has shown to increase the contact angle from 54° to 80° and 295 In Green Polymer Chemistry: Biocatalysis and Materials II; Cheng, H., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 2013.


to impart antimicrobial properties to the PLA films (18). An obvious, but to date untested extension of this work would be to extend these methodologies to the direct fluorination of PLA and PHA polymeric materials.

Figure 5. Bacterially synthesized fluoro-functionalized PHA polymers. Direct fluorination, a process whereby gaseous fluorine (F2) is utilized to functionalize a surface, exchanges C-H bonds for C-F bonds, producing HF as a byproduct. Direct fluorination is a surface technique, functionalizing to a depth of 0.01 to 10 µm, while leaving the bulk unchanged. This process often results in enhanced chemical resistance, and improved barrier properties, however as fluorine is an aggressive oxidant, it may also result in lower molecular weight (19) due to oxidative degradation of the polymer chains.

Direct Fluorination General Procedure for Direct Fluorination Using 5% F2 in a N2 Gas Mixture Direct fluorination was carried out at room temperature in a stainless steel flow reactor designed and built in our lab. A picture of the reactor (top) as well as a schematic diagram (bottom) of the reactor are shown in the Figure 6. The reactor is composed of a stainless steel vessel equipped with a pressure gauge (up to 60 psi) and removable lid mounted on shaker and connected via flexible tubing to the reactive (5% F2/N2) and purge (N2) gases. N2 and 5% F2/N2 gas are connected upstream to the reactor with a scrubber (equipped with soda lime pellets), vacuum and bubbler (filled with fluorinated oil) downstream. This setup facilitates the evacuation, loading and purging of the system with minimal opportunity for leakage of F2. 296 In Green Polymer Chemistry: Biocatalysis and Materials II; Cheng, H., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 2013.


Figure 6. Picture (top) and schematic diagram (bottom) of the direct fluorination reactor at The University of Texas at Dallas.



A Typical Procedure Samples to be fluorinated are dried (often in a vacuum oven or vacuum dessicator for 24 h) and then transferred into the stainless steel fluorination reactor which is sealed with the aid of a fluorinated lubricant (applied around the door of the reactor). The system is then evacuated, purged with nitrogen (until positive pressure is observed in the reactor gauge), evacuated again, and finally charged with fluorine to the desired pressure. The system is then sealed and set to agitate for the allotted time of the reaction. Once complete, the reaction is pacified by slowly venting the remaining F2 and evolved HF through a scrubber and testing the effluent for excess corrosive gas (with KI paper). The system is finally purged with a steady flow of nitrogen after which the reaction vessel is opened and the reactants removed.

Fluorination of PHA Polymers Fluorination was performed using dilute F2 gas at room temperature in the described reactor utilizing the general procedure previously described (vide supra). Specific details are as follows: PHA = Poly(3-hydroxybutyrate-co)hydroxyhexanoate, F2 gas was at a concentration of 3-5% diluted in N2. The reaction was performed at 20 psi for 24 h.

Evidence of Fluorination While fluorination is generally considered a surface modification technique, visible changes were observed in the bulk of the PHA sample. Whereas the starting material was white and powdery in appearance, the fluorinated product appeared creamy yellow in color with a sticky, almost gummy, consistency. Solubilization in chloroform, an excellent solvent for PHA, was attempted and insoluble material was removed. FTIR of the insoluble material was complex and was set aside. The following discussion pertains to the soluble component of the reaction product. Spectroscopic analyses of the fluorinated PHA (F-PHA) was attempted by both XPS (atomic analysis) as well as FTIR and NMR spectroscopies (functional group analysis). XPS analysis of the neat PHA versus F-PHA shows a new peak at 700 eV corresponding to the F1s electron in the F-PHA sample (Figure 7A). Analysis of this peak reveals a 5 % fluorine composition of F-PHA compared to its complete absence in neat PHA. Further, ATR-FTIR of the F-PHA revealed the formation of new peaks around 1300 cm-1, 700 cm-1 and 1180 cm-1. These absorbances correspond to vibrational modes of -CF3 and -CF2- moieties, suggesting the fluorination of PHA. An overlay of neat PHA and F-PHA is shown in Figure 7B. It is worth noting that these results are in good agreement with the aforementioned study performed by Guerrouani et al (2007) (17). Finally, 19F-NMR shows clear peaks at -75, -83, -114, -123 and -127 ppm corresponding to terminal and methylene perfluorinated and fluorinated alkanes, no such absorbances are observed in the neat PHA. These analyses clearly indicate the 298 In Green Polymer Chemistry: Biocatalysis and Materials II; Cheng, H., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 2013.


presence of fluorine into a variety of chemical environments within the F-PHA structure. Analysis into the specific mechanism of the fluorination of PHA is currently ongoing.

Figure 7. XPS (A) and ATR-FTIR (B) spectra of neat PHA and F-PHA.



Effect of Fluorination Substantial changes in the physical and thermal properties of PHA were observed post fluorination. A dramatic decrease in the molecular weight of F-PHA was observed from an initial Mn = ~126 KDa (neat PHA) to a Mn = ~13 KDa. The reason for this decrease is still under investigation, however the prevailing theories focus around F2 mediated chain scission or HF catalyzed hydrolysis of the ester functionalities along the PHA backbone (17, 20). The effect of this decreased molecular weight can be observed in the TGA where the thermal stability of the F-PHA is decreased substantially. While ultimate degradation remained near 300 °C, the onset of degradation began much sooner around 120 °C (N2) or 50 °C (Air) (Figure 8). Indeed, the DSC analysis of this material shows a complete loss of thermal properties. Whereas neat PHA possesses transitions at -1 °C (Tg), 62 °C (Tc) and, 126 and 145 °C (Tm), F-PHA shows no discernible thermal transitions. These changes in the thermal properties of the F-PHA can be attributed to the tenfold decrease in its molecular weight and are potentially useful for applications which require enhanced degradation at lower temperatures.

Figure 8. TGA (left) and DSC (right) of PHA and F-PHA in nitrogen.

Future Prospective F-PHA materials are of much current interest as compatibilizing agents for fluoropolymers with aliphatic polyester (PLA, PHA) polymers, especially for biomedical devices. Successful fluorination of PHA polymers using fluorine gas was achieved forming low molecular F-PHA. Exploration of the specific mechanism of fluorination and chain scission is currently ongoing as well as studies on the efficacy of F-PHA as a compatibilizing agent in blended systems and degradation studies including hydrolysis (in neutral and acid/base conditions). 300 In Green Polymer Chemistry: Biocatalysis and Materials II; Cheng, H., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 2013.

Acknowledgments The authors would like to thank the Robert A. Welch Foundation (Grant AT-0041), the Alan G. MacDiarmid NanoTech Institute, the Center for Energy Harvesting Materials and Systems (NSF-I/UCRC, Grant 1035024) and the University of Texas at Dallas for their generous support. We would also like to thank Proctor and Gamble Co. for kindly supplying PHA samples under the trade name, NODAX.


References 1. 2. 3. 4. 5. 6. 7. 8. 9. 10. 11. 12. 13. 14. 15. 16. 17. 18. 19. 20.

Garlotta, D. J. Polym. Environ. 2001, 9, 63. Chen, G. Q.; Wu, Q. Biomaterials 2005, 26, 6565. Drumright, R. E.; Gruber, P. R.; Henton, D. E. Adv. Mater. 2000, 12, 1841. Perego, G.; Cella, G. D.; Bastioli, C. J. Appl. Polym. Sci. 1996, 59, 37. Lasprilla, A. J. R.; Martinez, G. A. R.; Lunelli, B. H.; Jardini, A. L. Biotechnol. Adv. 2012, 30, 321. Wu, M.; Kleiner, L.; Tang, F. W.; Hossainy, S.; Davies, M. C.; Roberts, C. J. Drug Delivery 2010, 17, 376. Anderson, A. J.; Dawes, E. A. Microbiol. Rev. 1990, 54, 450. Takagi, Y.; Yasuda, R.; Maehara, A.; Yamane, T. Eur. Polym. J. 2004, 40, 1551. Scheirs, J. Modern Fluoropolymers: High Performance Polymers for Diverse Applications; Wiley: New York, 1997. Lee, W. K.; Losito, I.; Gardella, J. A., Jr; Hicks, W. L., Jr. Macromolecules 2001, 34, 3000. Edmonds, W. F.; Hillmyer, M. A.; Lodge, T. P. Macromolecules 2007, 40, 4917. Bongiovanni, R.; Malucelli, G.; Messori, M.; Pilati, F.; Priola, A.; Tonelli, C.; Toselli, M. J. Polym. Sci., Part A: Polym. Chem. 2005, 43, 3588. Haynes, D.; Naskar, A. K.; Singh, A.; Yang, C. C.; Burg, K. J.; Drews, M.; Harrison, G.; Smith, D. W., Jr. Macromolecules 2007, 40, 9354. Singh, A.; Naskar, A. K.; Haynes, D.; Drews, M. J.; Smith, D. W., Jr. Polym. Int. 2011, 60, 507. Frediani, M.; Rosi, L.; Camaiti, M.; Berti, D.; Mariotti, A.; Comucci, A.; Vannucci, C.; Malesci, I. Macromol. Chem. Phys. 2010, 211, 988. Giuntoli, G.; Rosi, L.; Frediani, M.; Sacchi, B.; Frediani, P. J. Appl. Poly. Sci. 2012, 125, 3125. Guerrouani, N.; Baldo, A.; Maarouf, T.; Belu, A. M.; Kassis, C. M.; Mas, A. J. Fluorine Chem. 2007, 128, 925. Boonyawan, D.; Sarapirom, S.; Tunma, S.; Chaiwong, C.; Rachtanapun, P.; Auras, R. Surf. Coat. Technol. 2011, 205, S552. Rand, A. A.; Mabury, S. A. Environ. Sci. Technol. 2011, 45, 8053. Lagow, R.; Wei, H.-C. In Fluoropolymers 1: Synthesis; Hougham, G., Cassidy, P., Johns, K., Davidson, T., Eds.; Springer New York: 2002; p 209. 301 In Green Polymer Chemistry: Biocatalysis and Materials II; Cheng, H., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 2013.

Direct Fluorination of Poly(3-hydroxybutyrate-co) - American Chemical

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