个人简介

Education B.A. 1990, Cornell University Ph.D. 1994, Harvard University NIH Postdoctoral Research Fellow, UCLA, 1995-1997 AWARDS & HONORS American Chemical Society PROGRESS/Dreyfus Lectureship Award (Camille and Henry Dreyfus Foundation Special Grant Program in the Chemical Sciences) NSF CAREER Award Alfred P. Sloan Fellow Faculty of Arts and Sciences Award for Distinguished Contributions to Undergraduate Education

研究领域

Analytical Chemistry/Biophysical Chemistry/Organic Chemistry

Biological and organic chemical reactivity, recognition, and catalysis Our group combines experimental and computational methods to understand mechanisms of reactions important for chemistry and biology. Specifically, we utilize traditionally physical methods, primarily mass spectrometry and computational chemistry, to tackle problems at the chemistry/biology interface, focusing on catalysis. We work on both biological catalysis, uncovering the mechanisms by which enzymes excise damaged DNA from the genome; as well as organic catalysis, examining N-heterocyclic carbenes as organocatalysts. profile_1b.pngOrganic catalysis. N-Heterocyclic carbenes (NHCs) are organic species that have a wide variety of applications, including as effective ligands for transition-metal-catalyzed reactions; as catalysts in their own right, for a range of organic transformations; and in protonated form, as environmentally "clean" (green) nonvolatile solvents for organic reactions (ionic liquids). Despite the widespread use of NHCs, their fundamental reactivity is not fully characterized. Our group has developed novel mass spectrometric methodology to measure the thermochemical properties and explore the reactivity of such carbenes. Recent work has provided the first experimental evidence for the high nucleophilicity of a series of diamidocarbenes, which are newly designed NHCs that display both nucleophilic and electrophilic properties (in collaboration with Professor Christopher Bielawski, UT Austin). We are also working on elucidating the mechanism of the Stetter reaction, a highly useful synthetic transformation catalyzed by NHCs. This work will contribute to the design and understanding of new carbene scaffolds and the development of new catalysts for organic transformations. profile_2b.pngBiological catalysis. DNA reactivity and stability are critical issues for all living beings. The heterocyclic bases of nucleic acids are targets for toxins that damage DNA, events that are linked to carcinogenesis and cell death. A family of enzymes called DNA glycosylases protect the human genome from the lethal effects of mutated DNA by the base excision repair pathway. We have developed a hypothesis to explain how certain glycosylases differentiate normal from damaged bases. Various lines of evidence have led to the conclusion that glycosylases achieve selectivity by providing a hydrophobic environment that helps differentiate normal from damaged DNA bases. The gas phase is the "ultimate" hydrophobic environment, and our studies of reactions by calculations and novel mass spectrometry methods reveal intrinsic reactivity that is relevant to biological hydrophobic environments such as enzyme active sites. The group is also embarking on enzyme kinetics studies to test hypotheses regarding glycosylase mechanisms. Given the cytotoxic and mutagenic effects of DNA damage, this work has broad implications for aging and for diseases including cancer.

近期论文

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Chen, M.; Lee, J. K. "Computational Studies of the Gas-Phase Thermochemical Properties of Modified Nucleobases," J. Org. Chem., 2014, in press. Zeng, H.; Wang, K.; Tian, Y.; Niu, Y.; Greene, L.; Hu, Z.; Lee, J. K. "The Benzoin Condensation: Charge Tagging of the Catalyst Allows for Tracking by Mass Spectrometry," Int. J. Mass. Spectrom., 2014, 369, 92-97. Wang, K.; Chen, M.; Wang, Q.; Shi, X.; Lee, J. K. "1,2,3-Triazoles: Gas Phase Properties," J. Org. Chem., 2013, 78, 7249-7258. Chen, M.; Moerdyk, J. P.; Blake, G. A.; Bielawski, C. W.; Lee, J. K. "Assessing the Proton Affinities of N,N'-Diamidocarbenes," J. Org. Chem., 2013, 78, 10452–10458 ("Highlighted Article") Maiti, A.; Michelson, A. Z.; Hwang, B.-J.; Armwood, C. J.; Lu, A.-L.; Lee, J. K.; Drohat, A. C. "Divergent Mechanisms for TDG Excision of 5-Formylcytosine and 5-Carboxylcytosine from DNA," J. Am. Chem. Soc., 2013, 135, 15813-15822. Michelson, A. Z.; Rozenberg, A.; Tian, Y.; Sun, X.; Davis, J.; Francis, A. W.; O'Shea, V. L.; Halasyam, M.: Manlove, A. H.; David, S. S.; Lee, J. K. "Gas-Phase Studies of Substrates for the DNA Mismatch Repair Enzyme MutY," J. Am. Chem. Soc., 2012, 134, 19839-19850. Michelson, A. Z.; Chen, M.; Wang, K.; Lee, J. K. "Gas-Phase Studies of Purine 3-Methyladenine DNA Glycosylase II (AlkA) Substrates," J. Am. Chem. Soc., 2012, 134, 9622-9633. Michelson, A. Z.; Petronico, A.; Lee, J. K. "2-Pyridone and Derivatives: Gas Phase Acidity, Proton Affinity, Tautomer Preference and Leaving Group Ability," J. Org. Chem., 2012, 77, 1623-1631. Liu, M.; Chen, M.; Zhang, S.; Yang, I.; Buckley, B.; Lee, J. K. "Reactivity of Carbene•Phosphine Dimers: Proton Affinity Revisited," J. Phys. Org. Chem. 2011, 24, 929-936. Lee, J. K.; Tantillo, D. J. "Reaction Mechanisms: Pericyclic Reactions," Annu. Rep. Prog. Chem., Sect. B 2011, 107, 266-286. Liu, M.; Tran, N. T.; Franz, A. K.; Lee, J. K. "Gas-Phase Acidity Studies of Dual Hydrogen-Bonding Organic Silanols and Organocatalysts," J. Org. Chem. 2011, 76, 7186-7194. Liu, M.; Yang, I.; Buckley, B.; Lee, J. K. "Proton Affinities of Phosphines versus N-Heterocyclic Carbenes," Org. Lett. 2010, 21, pp 4764–4767. Lee, J. K.; Tantillo, D. J. "Reaction Mechanisms: Pericyclic Reactions," Annu. Rep. Prog. Chem., Sect. B 2010, 106, 283-303. Sun, X.; Lee, J. K. "The Stability of DNA Duplexes Containing Hypoxanthine (Inosine): Gas versus Solution Phase and Biological Implications," J. Org. Chem., 2010, 75, 1848-1854. Zhachkina, A.; Lee, J. K. "Uracil and Thymine Reactivity in the Gas Phase: The SN2 Reaction and Implications for Electron Delocalization in Leaving Groups," J. Am. Chem. Soc. 2009, 131, 18376-18385. Zhachkina, A.; Liu, M.; Sun, X.; Amegayibor, F. S.; Lee, J. K. "Gas-Phase Thermochemical Properties of the Damaged Base O-Methylguanine versus Adenine and Guanine," J. Org. Chem. 2009, 74, 7429-7440. Tantillo, D. J.; Lee, J. K. "Reaction Mechanisms: Pericyclic Reactions," Annu. Rep. Prog. Chem., Sect. B, 2009, 105, 285-309. Liu, M; Li, T.; Amegayibor, F. S.; Cardoso, D. S.; Fu, Y.; Lee, J. K. "Gas-Phase Thermochemical Properties of Pyrimidine Nucleobases," J. Org. Chem. 2008, 73, 9283-9291. Rozenberg, A; Lee, J. K. "Theoretical Studies of the Quinolinic Acid to Nicotinic Acid Mononucleotide Transformation," J. Org. Chem. 2008, 73, 9314-9319. Wepukhulu, W. O.; Smiley, V. L.; Vemulapalli, B.; Smiley, J. A.; Phillips, L. M.; Lee, J. K. "Evidence for Pre-Protonation in the Catalytic Reaction of OMP Decarboxylase: Kinetic Isotope Effects using the Remote Double Label Method," Organic and Biomolecular Chemistry 2008, 6, 4533-4541 (ALSO FEATURED ON COVER).