Supramolecular architectures in two 1:1 cocrystals of 5-fluorouracil with 5-bromothiophene-2-carboxylic acid and thiophene-2-carboxylic acid

Abstract

In solid-state engineering, cocrystallization is a strategy actively pursued for pharmaceuticals. Two 1:1 cocrystals of 5-fluorouracil (5FU; systematic name: 5-fluoro-1,3-dihydropyrimidine-2,4-dione), namely 5-fluorouracil-5-bromothiophene-2-carboxylic acid (1/1), CHBrOS·CHFNO, (I), and 5-fluorouracil-thiophene-2-carboxylic acid (1/1), CHFNO·CHOS, (II), have been synthesized and characterized by single-crystal X-ray diffraction studies. In both cocrystals, carboxylic acid molecules are linked through an acid-acid R(8) homosynthon (O-H...O) to form a carboxylic acid dimer and 5FU molecules are connected through two types of base pairs [homosynthon, R(8) motif] via a pair of N-H...O hydrogen bonds. The crystal structures are further stabilized by C-H...O interactions in (II) and C-Br...O interactions in (I). In both crystal structures, π-π stacking and C-F...π interactions are also observed.