Light-responsive compounds have been used to manipulate biological systems with spatial and temporal control of the event of interest. Illumination of alkylcobalamins with green light (>500 nm) produces carbon-centered radicals, which have been demonstrated to effectively cause DNA damage. Molecules that cause DNA and RNA strand scission are useful for studying polynucleotide structure and the binding of small molecules and proteins to polynucleotides. Most molecules that cause DNA damage in a light-dependent manner require high energy, short wavelength ultraviolet light, which is readily absorbed by nucleotide bases causing damage to the polynucleotides. Therefore, using alkylcobalamins is advantageous for causing strand scission of polynucleotides, because they are activated by light wavelengths that are not absorbed by nucleotide bases. Green-light illumination of methylcobalamin effectively causes DNA strand scission based on gel mobility assays. This cleavage is due to the generation of carbon-centered radicals based on the results of a radical trapping study. In addition, synthesis of an alkylcobalamin with a DNA binding moiety, spermine, improves DNA cleavage efficacy by an order of magnitude in comparison with methylcobalamin.

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