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Photoinduced ring opening reactions and subsequent thermal ring closure reactions in the thymine—ammonia system and related systems

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Abstract

The photo-induced ring opening reactions of thymine (Thy) and 1-methylthymine (MeT) with ammonia and with methylamine (MA) at basic pH, and the subsequent ring closure reactions of the resulting adducts, have been studied. In the photo-induced reaction of Thy with ammonia, the dominant product is the E form of N-carbamoyl-3-amino-2-methylacrylamide (IIIa). Heating or acid treatment of aqueous IIIa results in rapid formation of Thy as final product, while allowing IIIa to stand at 4 °C produces Thy and two isomeric Thy hydrates, namely trans- and cis-6-hydroxy-5,6-dihydrothymine (Ia and IIa). The main products in the other reactions have analogous structures and undergo analogous ring closure reactions. Incubation of IIIa (and similar adducts) in phosphate buffer near pH 7 significantly enhances the rate of hydrate formation; other weak acid/conjugate base buffer systems also increase the rate of hydrate formation. A mechanism leading from opened ring adduct (e.g.IIIa) to hydrates (e.g.Ia and IIa) is proposed; ring closure leads initially to a dihydrothymine intermediate containing a 6-amino moiety, while further reaction with water produces the observed hydrates. The results described may be relevant to understanding the fate of cross-links generated by photo-induced reaction of thymine moieties in DNA with lysine residues in nuclear proteins (e.g. histones) when they are formed in a cellular environment. Decomposition of such cross-links, catalyzed by cellular phosphate, could lead to production of thymine hydrates attached to lysine residues contained in the protein partner and concurrent generation of an apyrimidinic site in the DNA partner.

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Authors and Affiliations

  1. Department of Pharmaceutical Chemistry, School of Pharmacy, University of California, San Francisco, CA 94143-0446, USA

    Martin D. Shetlar

  2. City of Hope, Beckman Research Institute, Molecular and Cell Biology, 1500 East Duarte Road, Duarte, CA, 91010, USA

    Janet Chung

  3. Department of Pharmaceutical Sciences, School of Pharmacy, University of Maryland, 20 Penn Street, Baltimore, MD, 21201, USA

    Kellie Hom

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  1. Martin D. Shetlar
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  2. Janet Chung
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Correspondence to Martin D. Shetlar.

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Shetlar, M.D., Chung, J. & Hom, K. Photoinduced ring opening reactions and subsequent thermal ring closure reactions in the thymine—ammonia system and related systems. Photochem Photobiol Sci 9, 1228–1243 (2010). https://doi.org/10.1039/c0pp00144a

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