Hydrolysis and Atmospheric Oxidation Reactions of Perfluorinated Carboxylic Acid Precursors by Derek A. Jackson A thesis submitted in conformity with the requirements for the degree of Doctor of Philosophy Graduate Department of Chemistry University of Toronto © Copyright by Derek A. Jackson 2013 Hydrolysis and Atmospheric Oxidation Reactions of Perfluorinated Carboxylic Acid Precursors Derek Andrew Jackson Doctor of Philosophy Department of Chemistry University of Toronto 2013 Abstract This dissertation explores a number of different environmentally relevant reactions that lead to the production of perfluorocarboxylic acids (PFCAs), a family of environmental pollutants that does not undergo any further degradation pathways. The compound perfluoro-2-methyl-3-pentanone (PFMP) is a new fire fighting fluid developed by 3M that is designed as a Halon replacement. The environment fate of PFMP with regards to direct photolysis, abiotic hydrolysis and hydration was determined using a combination of laboratory experiments and computational modeling. PFMP was found to undergo direct photolysis giving a lifetime of 4-14 days depending on latitude and time of year. Offline samples confirmed PFCA products and a mechanism was proposed. Polyfluorinated amides (PFAMs) are a class of chemicals produced as byproducts of polyfluorinated sulfonamide synthesis via electrochemical fluorination (ECF). Using synthesized standards of four model compounds, PFAMs were detected and quantified in a variety of legacy commercial materials synthesized by ECF. PFAMs were hypothesized to undergo biological hydrolysis reactions, suggesting their importance as historical PFOA precursors. ii The PFAMs were also investigated with regards to their environmental fate upon atmospheric oxidation. Using a smog chamber, the kinetics and degradation mechanisms of N- ethylperfluorobutyramide (EtFBA) were elucidated. The lifetime of EtFBA to oxidation by OH was found to be approximately 4 days. Using offline sampling, PFAMs were shown to give PFCAs upon atmospheric oxidation and a plausible mechanism was proposed involving an initial N-dealkylation step followed by loss of isocyanic acid to give a perfluorinated radical. The perfluorinated radical then produces PFCAs by a series of known atmospheric reactions. Finally, the biological hydrolysis of the polyfluoroalkyl phosphate monoesters (monoPAPs) were studied in vitro using a bovine alkaline phosphatase enzyme. Michaelis- Menten kinetic parameters were measured and compared to hexyl phosphate. It was discovered that monoPAPs hydrolyzed on average 100 times faster than hexyl phosphate due to the electron withdrawing fluorine substituents. The results were also used to rationalize the results of a previous in vivo study which suggested monoPAPs were rapidly hydrolyzed in the small intestines of rats following a high dose by oral gavage. iii Acknowledgments The successful completion of this thesis is a testament to the many people who have given me support and encouragement over the many decades I have been a graduate student. It is thanks to all these people along with many others not mentioned herein that I will finally cease to be a student and venture into a new world. I wish to thank the members of my supervisory committee, Jennifer Murphy and Mark Taylor, for assisting me during my time as a graduate student, providing ideas, attending committee meetings and providing comments on my thesis. Thanks also goes to Jon Abbatt and Lynn Roberts of Johns Hopkins University for serving on my final defense committee and providing additional feedback on my dissertation. In particular I wish to thank my supervisor, Scott Mabury, for being a fantastic boss and role model during my time here. Scott’s enthusiasm for chemistry and molecular architecture is contagious and he is full of good ideas that have led to fruitful projects and publications in high impact journals. Thanks goes out to my co-authors on the various publications that comprise this dissertation: Cora Young, Michael Hurley and Timothy Wallington. In particular I must thank Tim Wallington for hosting me at Ford where together we completed perhaps the most productive scientific week I’ve ever had! Tim, you are a fantastic scientist and mentor and I hope to collaborate with you again in the near future. In the Department of Chemistry we are fortunate to have many skilled technical staff members who tirelessly work to ensure that students have access to the many shared resources we have. In addition, I am thankful to have developed friendships with many of them. From chemical stores I wish to thank Ken Greaves and Jim Gorrie for reliving countless episodes of iv The Simpsons and Family Guy as I wander through their domain. Also, thanks to Jim for endless discussions about Russian-built aircraft and where to find decent shrubberies. My thanks to Nasrin Manouchehri for being such a sympathetic listener and friend when the going got tough. Thank you Matthew Forbes, manager of AIMS, for keeping me motivated and asking me how my thesis is going (it’s basically done now!) From the NMR labs, thanks to Timothy Burrow, Darcy Burns, Dmitry Pichugin, Joel Tang and Adina Golombek for tirelessly working to ensure the NMR spectrometers are working and shimmed properly. From deep within the ANALEST labs, thanks to Dan Mathers for valuable advice on my instrumental challenges (although Agilent instruments are still superior to Perkin-Elmer instruments!) and for being a friend that I can chat with about Star Trek, The Big Bang Theory and The Simpsons. Thanks as well goes to the machine shop, managed by John Ford. Throughout my tenure as a member of the Mabury Lab, I have seen many students come and go over the years and all of them deserve my thanks for their friendship and scientific advice. Jessica D’eon, you’re a terrific friend who has always helped me out and encouraged me to see the brighter side of things…. it IS weird! Cora Young, your knowledge about literally everything and your ability to churn out paper after paper has always inspired me as a scientist. Thanks also for being a close friend and desk neighbour in LM318 for so many years, it was unforgettable! Craig Butt, thanks for your friendship and countless pieces of advice on all things life-related. From you, I learned to be more attentive to details and to take things more carefully with my experiments so I get the best results possible. “We know what we did”. Amila De Silva, thank you very much for being a supportive friend and a great listener when I had to vent about certain issues. I wish you, Perry and Indus all the best! Thanks to Shona Robinson for always keeping me on my toes about all things undergraduate-chemistry related and for being such a v delightful person to be around in general. Keegan Rankin, your awesome “cool as a cucumber” persona has always been a welcome presence in our lab, especially when things start to get stressful – good luck with all those fluorinated polymers! Thanks to Angela Hong for being a good friend and labmate and for going planespotting with me. Your ability to persevere with challenging projects and experiments and for venturing into the scary realm of atmospheric science is so admirable. “Robbie Di” Lorenzo, thanks for helping to keep things humourous in the lab and also for your advice on all things food related! Thanks to Lisa D’Agostino for all her advice on analytical chemistry techniques and reminding me of the nutritional value of carrots. To Leo Yeung, thanks for your kindness over the years whenever I had questions on anything related to analytical techniques, blanks, internal standards and so forth. Your ability to use and troubleshoot instrumentation is legendary around these parts. I also greatly appreciated your help with the LC-MS/MS analyses I had to do for my Ford project. To those people I didn’t know for very long such as Monica Lam, Naomi Stock, Erin Marchington, Barbara Weiner, Rui Guo, Rene-Christian Bouillon and Jan Jablonksi, thanks for everything and I wish you all the best. Thank you Anne Myers! You are a wonderful person who I will miss seeing on a day-to- day basis. From you, I have strived to be a more organized scientist and to “look before I leap” when it comes to planning experiments and interpreting the results. Thanks also for being my “running coach” when I was training for the 5k run at the airport, that was a lot of fun! I also love how your laugh is at least 30 dB higher than your normal speaking voice. Good luck with finishing your PhD!! Thank you Holly Lee! I am already missing your presence in our lab. You are one of the most talented scientists I have ever met. Your knack for setting up and performing experiments involving hundreds of samples, extractions, LC injections and trace level quantification is vi something I could never hope to achieve. I am still in awe of your ability to use the LC-MS/MS so skillfully and to never give up when the sensitivity goes down or the source gets dirty. You have also been a great friend over the years and I still remember the first time I met you in the summer of 2007. From that point, and also when I TA’d you in CHM410, I knew what a gifted person you are and that there was no limit to what you could accomplish! Thank you Amy Rand! You are one in a googol for sure. Your delightful, easy-going personality and good friendship is one of the reasons I made it this far. You are definitely one of the most multi-talented people I’ve known with an ability to analyze fluorotelomer unsaturated aldehyde reactions with proteins as easily as you play Bach fugues on a church organ.