Dehalogenation of Halogenated Nucleobases and Nucleosides by Organoselenium Compounds.

Halogenated nucleosides, such as 5‐iodo‐2′‐deoxyuridine and 5‐iodo‐2′‐deoxycytidine, are incorporated into the DNA of replicating cells to facilitate DNA single‐strand breaks and intra‐ or interstrand crosslinks upon UV irradiation. In this work, it is shown that the naphthyl‐based organoselenium compounds can mediate the dehalogenation of halogenated pyrimidine‐based nucleosides, such as 5‐X‐2′‐deoxyuridine and 5‐X‐2′‐deoxycytidine (X=Br or I). The rate of deiodination was found to be significantly higher than that of the debromination for both nucleosides. Furthermore, the deiodination of iodo‐cytidines was found to be faster than that of iodo‐uridines. The initial rates of the deiodinations of 5‐iodocytosine and 5‐iodouracil indicated that the nature of the sugar moiety influences the kinetics of the deiodination. For both the nucleobases and nucleosides, the deiodination and debromination reactions follow a halogen‐bond‐mediated and addition/elimination pathway, respectively. DNA photosensitizers: Dehalogenation of halogenated nucleosides, which are potential DNA photosensitizers, by organoselenium compounds is described (see picture). Attachment of 2′‐deoxyribose or ribose sugar to the halogenated nucleobases significantly enhances the rate of deiodination reactions. The Se⋅⋅⋅I halogen bonding plays an important role in the kinetics of the deiodination reactions. [ABSTRACT FROM AUTHOR]