Solid-State Photochemical Reaction of Multisubstituted Thymine Derivatives

Solid-state photochemical
reactions in crystals, known as topochemical
reactions, are solvent-free green chemical reactions that produce
stereospecific molecules. The photoreaction of thymine is interesting
because the dimeric photoproduct can form four types of stereoisomers
and when the dimer is formed in DNA helices it can cause skin cancers.
We investigated the photoreaction of five multisubstituted thymine
derivatives in the solid-state, which were designed with crystal engineering
concepts to promote π–π stacking of benzene rings
in the crystal. Powder X-ray diffraction analysis revealed that a para-substituted bis-thymine derivative was aligned along
the c axis in the crystal and was susceptible to
topochemical reaction to form a polymer, as previously reported. Ortho- and meta-substituted bis-thymine
derivatives and a tetrakis-substituted derivative were found to be
topochemically unreactive using both gel permeation chromatography
(GPC) and X-ray crystal structural analysis. The tris-substituted
thymine derivative was found to be topochemically reactive due to
favorable crystal packing, which included ethanol molecules to form
hydrogen bonding with one of the thymine moieties and stabilize the
crystal packing. GPC and crystal structural analysis revealed that
it could form tetramer at most via topochemical [2+2]-cycloaddition
upon UV irradiation. Based on the crystal structure of the tris-substituted
thymine derivative, the structure of the tetrameric photoproduct is
expected to link via cis–syn, trans–anti and cis–syn cyclobutane isomers.