Office: MEYR 549A
Photochemical probes of macromolecular structure.
Advances in genomics and proteomics require new tools in molecular biology. In our laboratory, we are developing synthetic organic and inorganic molecules as structural probes of DNA and proteins. Through molecular engineering, we synthesize the compounds to recognize and bind to specific DNA sequences or protein residues. To date, we have used naphthalimide derivatives that are readily synthesized and functionalized. Upon activation with UV or visible light, the compounds initiate a sequence of chemical events that lead to cleavage of the macromolecule at the binding site. In parallel, transient laser spectroscopy is used to understand reaction mechanisms. Once the fragments are identified using HPLC and mass spectrometry, the DNA or protein structure may be reconstructed. Thus, these ‘photonucleases’ and ‘photoproteases’ provide new tools to identify the sequence and 3D structure of DNA and proteins.
Stimuli-responsive polymers find broad-ranging applications in smart materials and smart packaging applications. Our group is interested in building functionalized polymers that respond, via basic photophysical phenomena, to changes in external stimuli (temperature, pressure, etc.). Fundamentally, we are interested in gaining knowledge about how the polymer architecture governs, among other things, the thermal properties of the polymer. Traditional synthetic polymer chemistry is used to systematically build and functionalize the polymers. NMR, mass spectrometry, and DSC are used to characterize the materials. Steady-state and time-resolved fluorescence methods are used to understand the fundamental photophysics. Specifically, using time-correlated single-photon counting, the polymer dynamics and rate constants for excited-state interconversions, are mapped out to understand which elementary reaction step controls the temperature-dependent photophysics. As a result, systematic structure-function correlations are obtained.
- Manning, S. J.; Bogen, W.; Kelly, L. A. ‘Synthesis, Characterization, and Photophysical Study of of Fluorescent N-Substituted Benzo[ghi]perylene ‘Swallow Tail’ Monoimides,’ The Journal of Organic Chemistry,2011, 76, 6007-6013.
- Trexler, M. M.; Zhang, D.; Kelly, L.; Sample, J. ‘Crystal Structure and Optical Properties of Erbium- and Neodymium-Doped Zirconia Nanoparticles,’ Journal of Materials Research, 2010, 25, 500 – 509
- Arnold, B.; Kelly, L.; Oleske, J. B.; Schill, A. ‘Standoff Detection of Nitrotoluenes Using 213-nm Amplified Spontaneous Emission from Nitric Oxide,’ Analytical and Bioanalytical Chemistry, 2009, 395, 349-355.
- Schill, Alexander W.; Arnold, Bradley R.; Kelly, Lisa A.; Pellegrino, Paul, M. ‘Standoff Detection using Coherent Backscattered Spectroscopy,’ Proc. of SPIE, 2007, 6554, 6554G-1 – 6554G-8.
- McMasters, S. and Kelly, L. A. ‘Sequence-Dependent Interactions of Cationic Naphthalimides and Polynucleotides,’ Photochemistry and Photobiology, 2007, 83, 889 – 896.
- McMasters, S.; Kelly, L. A. “Ground-State Interactions of Spermine-Substituted Naphthalimides with Mononucleotides,” Journal of Physical Chemistry, B, 2006, 110, 1046-1055.
- Kimaro, A.; Kelly, L. A.; Murray, G. M., “Synthesis and Characterization of Molecularly Imprinted Uranyl Ion Exchange Resins,” Separation Science and Technology, 2005, 40, 2035–2052.
- Abraham, B.; McMasters S.; Mullan, M. A.; Kelly, L. A., ‘Reactivities of Carboxy-Substituted 1,4,5,8-Naphthalene Diimides in Aqueous Solution,’ Journal of the American Chemical Society, 2004, 126, 4293-4300.
- Chandrasekharan, N; Kelly, L. A., ‘Progress Towards Fluorescent Molecular Thermometers,’ in Reviews in Fluorescence 2004, Geddes, C. D., Editor, 2004, pgs. 21-40.
- Abraham, B.; Kelly, L., ‘Photo-oxidation of Amino Acids and Proteins Mediated by Novel 1,8-Naphthalimide Derivatives,’ J. Phys.Chem B 2003, 107, 12534 – 12541.
- Chandrasekharan, N.; Kelly, L., ‘Fluorescent Molecular Thermomemters Based on Monomer/Excimer Interconversion,’ The Spectrum 2002, 15, 1-7.
- Rogers, J. E.; Le, T. P.; Kelly, L. A., ‘Nucleotide Oxidation Mediated by Naphthalimide Excited States with Covalently Attached Viologen Cosensitizers,’ Photochem. Photobiol. 2001, 73, 223-229.
- Kimaro, A.; Kelly, L. A.; Murray, G. M., ‘Molecularly Imprinted Ionically Permeable Membrane for Uranyl Ion,’ Chemical Communications 2001, 1282 – 1283.
- Rogers, J. E.; Abraham, B.; Rostkowski, A.; Kelly, L. A., ‘Mechanisms of Photoinitiated Cleavage of DNA by 1,8-Naphthalimide Derivatives,’ Photochem. Photobio. 2001, 74, 521-531.
- Chandrasekharan, N. and Kelly, L. A. ‘A Dual Fluorescence Temperature Sensor Based on Perylene/Exciplex Interconversion,’ J. Am. Chem. Soc. 2001, 123, 9898-9899.
- Rogers, J. E.; Weiss, S. J.; Kelly, L. A., ‘Photoprocesses fo Naphthalene Imide and Diimide Derivatives in Aqueous Solutions of DNA,’ J. Am. Chem. Soc. 2000, 122, 427-436.
- Le, T. P.; Rogers, J. E.; Kelly, L. A., ‘Photoinduced Electron Transfer in Covalently Linked 1,8-Naphthalimide/Viologen Systems,’ J. Phys. Chem. A. 2000, 104, 6778-6785.
- Rogers, J. E.; Kelly, L. A., ‘Nucleic Acid Oxidation Mediated by Naphthlene and Benzophenone Imide and Diimide Derivatives: Consequences for DNA Redox Chemistry,’ J. Am. Chem. Soc. 1999, 121, 3854-3861.
- Morgana M. Trexler, Dajie Zhang, Lisa Kelly, Jennifer Sample . ‘Crystal structure and optical properties of erbium- and neodymium-doped zirconia nanoparticles’. Journal of Materials Research 25. 3 (2010)
Honors and Awards
- CHEM 303: Physical Chemistry for Biochemical Sciences
- CHEM 302: Physical Chemistry II
- CHEM 420: Computer Applications in Chemistry
- CHEM 443: Molecular Spectroscopy and Biomacromolecules
- CHEM 490: Special Topics in Chemistry – Applications of Photochemistry and Spectroscopy.
This course focuses on the fundamental aspects of photophysical and photochemical phenomena. Fundamental aspects of the creation and fate of electronically excited states are covered. The application of modern instrumentation to probe excited-state dynamics are emphasized. Topics include the theory and practical aspects of fluorescence and transient absorption spectroscopies. The course emphasizes the interaction of light with molecular systems to (i) initiate and understand important light-initiated reactions, including photosynthesis, vision, and nucleic acid photochemistry and (ii) develop practical sensors for use in biological and environmental applications. Prequisites: CHEM 302 or 303 and CHEM 352 or equivalent. NOTE: This course is also offered at the 600 level for graduate students.
- CHEM 499: Undergraduate Research
- CHEM 399: Tutorial Projects in Chemistry
- CHEM 420: Computer Applications in Chemistry
|Fluorescent dye synthesis (Yu and Matthew)|
|Nanosecond laser flash photolysis|
Photophysical Studies of Stimuli-Responsive Polymers.
Our group is broadly interested in fabricating and studying new polymers that have utility as stimuli-responsive materials. These materials are made by co-polymerizing a fluorescent dye with a variety of styrene or acrylamide co-monomers. Fundamental photophysics are used to tailor these materials for a response of choice. For example, to map temperature distributions in real time on any surface or object, we are fabricating polymeric coatings that exhibit exciplex or excimer formation. This phenomenon is characterized by a two-color emission. By imaging the intensities of each color, as a function of spatial coordinate, the precise temperature on each point of the object can by quantified and monitored in real time. At the same time, we are interested in developing polymeric coatings that exhibit a time-temperature response for smart packaging applications (like when has your milk jug been left too warm too long!). These materials take advantage fluorescence quenching, which can be thermally reversed via a chemical reaction in the polymer (i.e. your milk jug lights up under black light when it has risked spoiling!).
Photochemical Probes of Macromolecular Structure.
Complementary methods of transient laser spectroscopy and traditional bioanalytical methods are used to investigate the photocleavage and photomodification of proteins and DNA. Research projects begin with the synthesis of functionalized aromatic imides and diimides designed to photoinduce a specific kind of damage (cleavage, cross-linking, affinity labeling, etc.). Next, the photophysical and redox properties are assessed using transient and steady-state spectroscopy, along with electrochemical methods. Transient absorption spectroscopy is used to identify the early photochemical events with viable targets (nucleic acids and peptides or proteins). Finally, traditional bioanalytical methods are used to correlate the early photochemical events with the modified macromolecules. The complementary approach offers a fundamental understanding into the development of new small molecules that can be light-activated and serve as static and dynamic probes of macromolecular structure.