Pyrimidine derivatives have been studied extensively for participation in [2+2] photocycloadditions, as the reactions are known to be an important mechanism by which DNA is damaged from exposure to UV radiation. Among such derivatives, 5-Fluorouracil (5-FU) has been used almost ubiquitously as a chemotherapeutic agent in the treatment of many forms of cancer (e.g. colon, pancreatic, breast). However, [2+2] photocycloadditions involving 5-FU have focused primarily on the solution-phase synthesis of prodrugs and drug conjugates designed for controlled delivery.1 The crystallographic landscape of 5-FU stands underdeveloped and, as yet, there are no known examples of its photoreactivity in the solid state. Recently, investigations of 5-FU in the solid state have taken the first steps as cocrystals of 5-FU and N-based aromatic heterocycles have been reported.2 Here we explore the solid-state behavior of 5-FU in a series of cocrystals of 5-FU formed with bipyridine cocrystal formers. The hydrogen-bonding motifs of 5-FU within the cocrystals are similar to those of the pure 5-FU polymorphs. Additionally, the photoreactivity of the cocrystals was studied and a [2+2] cross-photodimerization observed. 1 Q. Jin, F. Mitschang and S. Agarwal, Biomacromolecules, 2011, 12, 3684. 2 A. Delori, M. D. Eddleston and W. Jones, CrystEngComm, 2013, 15, 73.

Solid-state chemistry and reactivity of a common anti-cancer drug

251st National Meeting (2016)

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