Copyright by Himali Sudarshani Hewage 2008 The Dissertation Committee for Himali Sudarshani Hewasge Certifies that this is the approved version of the following dissertation: STUDIES OF APPLYING SUPRAMOLECULAR CHEMISTRY TO ANALYTICAL CHEMISTRY Committee: Eric Anslyn, Supervisor Brent Iverson Christopher Bielawski John McDevitt Dean Neikirk STUDIES OF APPLYING SUPRAMOLECULAR CHEMISTRY TO ANALYTICAL CHEMISTRY by Himali Sudarshani Hewage, B.S.; M.A. Dissertation Presented to the Faculty of the Graduate School of The University of Texas at Austin in Partial Fulfillment of the Requirements for the Degree of Doctor of Philosophy The University of Texas at Austin December 2008 This dissertation is dedicated to my mother and father, my husband Damitha, and my daughter Sanaya for their love and support. Acknowledgements First and foremost my deepest gratitude is for You, my wonderful Research Advisor, Professor Eric Anslyn. I want to thank you most sincerely for welcoming me into your group and giving me the opportunity to complete my graduate career under your guidance and support. You have been such a blessing in my life and have helped me to accomplish many things that are important in my life apart from my educational goals. They say “true success is how many people’s lives are better off because you live”. You are a role model for that. I am truly in debt to you for always offering a helping hand and going that extra mile to do what ever you can do. I sincerely wish you and your family the very best and be blessed with most wonderful things in the world. A very special thank to Dr. Bauld for lifting me up and encouraging me when I needed it the most. Thank you very much for your love and support. I am grateful to all the members of the Anslyn research group, past and present for their support and guidance. Thank you Karl, and Ron for your collaborations on my projects and the many scientific discussions we had. Karl, you are just an email away, I really appreciate that you are always there to help and for your wonderful editing. Thank you Andrew for being a great and caring lab mate and I have found a great friend in you. Thank you Sonia and Shuhui for your love and friendship and we will always be friends. A big Thank you to Joseph for your special friendship, I always admire that. Marco, I really appreciate and thankful to you for helping me with this dissertation and the thoughtful discussions. You are awesome. v My dear husband, Damitha, thank you very much for all your love and support. You have been a tremendous support to me through out my undergraduate and graduate career. Without you none of this would have been possible. I feel blessed to be married to you. You are the wind beneath my wings. My daughter Sanaya, thank you for your love, hugs and smiles. You can make me do things. My mother, father, brother and sister, thank you very much for everything. This is for you. I am where I am today because of you. I love you all so much. vi STUDIES OF APPLYING SUPRAMOLECULAR CHEMISTRY TO ANALYTICAL CHEMISTRY Publication No._____________ Himali Sudarshani Hewage, Ph.D. The University of Texas at Austin, 2008 Supervisor: Eric V. Anslyn Supramolecular chemists can be thought of as architects, who combine individual non-covalently bonded molecular building blocks, designed to be held together by intermolecular forces to create functional architectures. Perhaps the most important assets of a supramolecular chemist, however, are imagination and creativity, which have given rise to a wide range of beautiful and functional systems. For years, analytical chemistry has taken advantage of supramolecular assemblies in the development of new analytical methods. The role of synthetic supramolecular chemistry has proven to be a key component in this multidisciplinary research. As such, the demand for synthetic receptors is rapidly increasing within the analytical sciences. The field “supramolecular analytical chemistry” involves analytical applications of synthetic organic and inorganic chemical structures that display molecular recognition properties and self-assembly but also signal vii these events. Chapter 1 presents an introduction to the background literature relevant to the central themes of the research presented in this thesis. The nonthermal production of visible light by a chemical reaction leads to the term “cool light”, and the process is called chemiluminescence. Although chemiluminescent reactions are not rare, the production of “cool light” holds such fascination for both chemists and nonchemists that demonstrations of chemiluminescent reactions are always well received. A glow assay technology for the detection of a chemical warfare simulant is presented in Chapter 2, which is based on modulating the peroxyoxalate chemiluminescence pathway by way of utilizing an oximate super nucleophile that gives an off–on glow response. As an alternative to highly analyte-specific synthetic receptors, trends in chemical sensing have shifted to the design of new materials and devices that rely on a series of chemo- or biosensors. The research relevant to Chapter 3 focuses on investigating the use of a single receptor, for sensing two different analytes; thiols and metal ions, utilizing a squaraine as the receptor in a sensor array format. The data is interpreted with principal component analysis. Finally Chapter 4 discusses an attempt to design and synthesize a chemosensor based on the luminophore-spacer-receptor format by incorporating the two concepts photoinduced electron transfer and peroxyoxalate chemiluminescence. viii Table of Contents List of figures.................................................................................................................... xii List of Schemes................................................................................................................ xiv 1. Studies of Applying Supramolecular Chemistry to Analytical Chemistry....................1 1.1. Introduction.............................................................................................................1 1.2. Non-covalent interactions.......................................................................................2 1.2.1. Electrostatic interactions..............................................................................2 1.2.2. Hydrogen bonding .......................................................................................3 1.2.3. π- π stacking forces ......................................................................................3 1.2.4. Dispersion forces .........................................................................................4 1.2.5. The hydrophobic effect................................................................................4 1.2.6. Classical coordination chemistry .................................................................5 1.3. Crown ethers...........................................................................................................5 1.4. Chemical Sensors....................................................................................................6 1.4.1. Photoinduced Electron Transfer (PET) systems..........................................9 1.4.2. Chemiluminescence ...................................................................................13 1.4.3. Indicator displacement assays (IDAs) .......................................................14 1.4.4. Multi-Analyte Sensing...............................................................................15 1.4.5. Principal Component Analysis (PCA).......................................................18 1.5. Summary and outlook...........................................................................................18 1.6. References for Chapter 1 ......................................................................................20 2. Chemiluminescent Detection of a Chemical Warfare Analog.....................................24 2.1. Nerve Agents ........................................................................................................24 2.2. Recent advances in various strategies used in the detection of nerve agents .......29 2.3. Chromo-fluorogenic sensing motifs for nerve agent detection ............................30 2.3.1. PET based fluorescent sensors...................................................................30 2.3.2. Oximate-containing sensors.......................................................................35 2.4. Chemiluminescence .............................................................................................39 2.4.1. Chemical light generation in solution........................................................40 ix 2.4.2. Chemically Initiated Electron Exchange Luminescence (CIEEL) ...........41 2.5. Applying POCL for detection of nerve gas analog DFP ......................................43 2.5.1. Our goal and design criteria.......................................................................43 2.5.2. Results and Discussion ..............................................................................43 2.5.2.1.Synthesis of oxime...............................................................................43 2.5.2.2.Inhibition of CL reaction in the presence of oximate nucleophile.......44 2.5.2.3.Turn “on” CL in the presence of nerve gas analog DFP......................45 2.5.2.4.NMR studies ........................................................................................45 2.5.2.5.Calibration Curves ...............................................................................46