Applications of physical-organic chemistry and photochemistry to biochemistry and materials science

 

 

 

Text Box: Two possible cyclization pathways of enediynes. Hydrogen atoms formally abstracted from the environment are blue italics Text Box: Suggested change in the DNA binding mode upon double protonation of lysine enediynes

 

 

 

 

 

 

 

 

 

 

Text Box: We developed an approach to efficient and selective DNA cleavage which is based on a new photochemical C1-C5 cyclization of enediynes discovered in our lab. This transformation involves two electron transfers, two proton transfers and two hydrogen abstractions (4H=2e+(2H+)+2H) – a sequence of six distinct chemical steps capable of modifying the structure of DNA. Since the cyclization is triggered by photoinduced electron transfer from DNA, light and binding to DNA are simultaneously required for the activation. Further control of reactivity is provided by pH-dependent binding and cleavage by lysine-enediyne conjugates. Increased reactivity at the lower pH can be used to increase selectivity of these molecules towards the more acidic cancer cells. C1-C5 cyclization of enediynes: Discovery: J. Am. Chem. Soc. 2002, 124, 9052. Theoretical analysis: J. Am. Chem. Soc. 2003, 125, 4495. Practical applications: Chem. Comm. 2005, 1444.  We have also designed a family of amino enediynes where the Bergman cyclization step is should display  ca.  600-50000 acceleration upon protonation. Ortho-substituted enediynes activated by protonation: J. Phys. Chem. A., 2003, 107, 3363-3371 (PDF); Org. Letters, 2002, 4, 1119-1122 (PDF) .        

 

 

 

 

 

 

 

 

 

 

 

 

 

Development of New Photochemical Reactions

 

pH-Activated Anticancer Agents

 

New Radical Reactions

 

Computational Chemistry

 

 

 
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