The long-term goal of this project is to understand the dynamics of excited states produced in DNA by the absorption of ultraviolet light. Knowledge of electronic relaxation pathways in nucleic acids is essential for understanding DNA photodamage at the molecular level. UV damage to DNA is responsible for a variety of adverse health effects, including immune suppression, photoaging, and skin cancer. Transient absorption by the nucleic acid bases, the UV chromophores of DNA and RNA, will be measured using the femtosecond pump-probe method. This technique has resulted recently in the first direct observations of singlet excited state dynamics in a series of nucleosides. Non-radiative decay occurs in hundreds of femtoseconds in these compounds, and is responsible for DNA's instrinsic photostability. This methodology will now be used to systematically study the mechanism of ultrafast non-radiative decay in cytosine monomers and in cytosine-containing di- and polynucleotides. Experiments will be done in different solvents and as a function of excitation wavelength. An emphasis will be on characterizing how base- base (base stacking and base pairing) and base-solvent interactions affect non-radiative decay in these model systems. A series of cytidine derivatives will be studied to understand how chemical substitution affects non-radiative decay. Minor bases such as 5-methylcytidine will be studied to identify bases with longer singlet state lifetimes. These will then be used to investigate the relations between monomers photophysical properties and those of the excimer states created in polynucleotides. This information will advance understanding of singlet energy transfer in DNA.
The specific aims of this project are: (1) To measure the singlet excited state dynamics for cytidine and a series of cytidine derivatives in aqueous solution at room temperature to learn how structure affects non- radiative decay and to identify new probes for time-resolved experiments. (2) The effects of solvent and excitation wavelength on the excited monophosphate, CpC, and the homopolymer poly(C) will be characterized and used to understand the microscopic factors that control excimer dynamics.
|de la Harpe, Kimberly; Crespo-Hernández, Carlos E; Kohler, Bern (2009) The excited-state lifetimes in a G x C DNA duplex are nearly independent of helix conformation and base-pairing motif. Chemphyschem 10:1421-5|
|de La Harpe, Kimberly; Crespo-Hernandez, Carlos E; Kohler, Bern (2009) Deuterium isotope effect on excited-state dynamics in an alternating GC oligonucleotide. J Am Chem Soc 131:17557-9|
|Hare, Patrick M; Middleton, Chris T; Mertel, Kristin I et al. (2008) Time-resolved infrared spectroscopy of the lowest triplet state of thymine and thymidine. Chem Phys 347:383-392|
|Takaya, Tomohisa; Su, Charlene; de La Harpe, Kimberly et al. (2008) UV excitation of single DNA and RNA strands produces high yields of exciplex states between two stacked bases. Proc Natl Acad Sci U S A 105:10285-90|
|Cohen, Boiko; Larson, Matthew H; Kohler, Bern (2008) Ultrafast excited-state dynamics of RNA and DNA C tracts. Chem Phys 350:165-174|
|Crespo-Hernandez, Carlos E; de la Harpe, Kimberly; Kohler, Bern (2008) Ground-state recovery following UV excitation is much slower in G x C-DNA duplexes and hairpins than in mononucleotides. J Am Chem Soc 130:10844-5|
|Law, Yu Kay; Azadi, Javad; Crespo-Hernandez, Carlos E et al. (2008) Predicting thymine dimerization yields from molecular dynamics simulations. Biophys J 94:3590-600|
|Schreier, Wolfgang J; Schrader, Tobias E; Koller, Florian O et al. (2007) Thymine dimerization in DNA is an ultrafast photoreaction. Science 315:625-9|
|Middleton, Chris T; Cohen, Boiko; Kohler, Bern (2007) Solvent and solvent isotope effects on the vibrational cooling dynamics of a DNA base derivative. J Phys Chem A 111:10460-7|
|Hare, Patrick M; Crespo-Hernandez, Carlos E; Kohler, Bern (2007) Internal conversion to the electronic ground state occurs via two distinct pathways for pyrimidine bases in aqueous solution. Proc Natl Acad Sci U S A 104:435-40|
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