Nucleic acids have been recognized as an important class of biomolecules for over half a century and are an integral component of many modern pharmaceuticals. Elucidating the associations between DNA nucleobases (thymine, cytosine, adenine and guanine) and other components in both solution and the solid state has wide-ranging applications. Far fewer thymine cocrystals have been reported compared to cocrystals of the other DNA bases. Using schemes inspired by Watson-Crick base pairing motifs, herein we investigate the cocrystallization of thymine and heterocycles with complementary hydrogen bond donors and acceptors. Our coformer screen yielded three new 1:1 cocrystals with thymine, only two of which exhibited the expected binding motif. The difficulties encountered in this nucleobase study serve to highlight some of the special challenges associated with cocrystallization of tautomeric components.
Bibliographical noteFunding Information:
The authors are grateful for financial support from the National Science Foundation under DMR awards 1306247 and 1609541, and CHE-MRI awards 0959546 and 1337975. K. A. M. thanks the Georgetown GUROP program for support. H. J. K. gratefully acknowledges financial support from the ACS-SEED program.