title: Supramolecular hydrogen-bonding patterns in 1:1 cocrystals of 5-fluorouracil with 4-methylbenzoic acid and 3-nitrobenzoic acid.
abstract: The design of a pharmaceutical cocrystal is based on the identification of specific hydrogen-bond donor and acceptor groups in active pharmaceutical ingredients (APIs) in order to choose a `complementary interacting' molecule that can act as an efficient coformer. 5-Fluorouracil (5FU) is a pyrimidine derivative with two N-H donors and C=O acceptors and shows a diversity of hydrogen-bonding motifs. Two 1:1 cocrystals of 5-fluorouracil (5FU), namely 5-fluorouracil-4-methylbenzoic acid (5FU-MBA), C4H3FN2O2·C8H8O2, (I), and 5-fluorouracil-3-nitrobenzoic acid (5FU-NBA), C4H3FN2O2·C7H5NO4, (II), have been prepared and characterized by single-crystal X-ray diffraction. In (I), the MBA molecules form carboxylic acid dimers [R22(8) homosynthon]. Similarly, the 5FU molecules form two types of base pair via a pair of N-H...O hydrogen bonds [R22(8) homosynthon]. In (II), 5FU interacts with the carboxylic acid group of NBA via N-H...O and O-H...O hydrogen bonds, generating an R22(8) ring motif (heterosynthon). Furthermore, the 5FU molecules form base pairs [R22(8) homosynthon] via N-H...O hydrogen bonds. Both of the crystal structures are stabilized by C-H...F interactions.
authors.affiliation: School of Chemistry, Bharthidasan University, Tiruchirappalli 620 024, Tamilnadu, India.
authors.forename: Marimuthu
authors.initials: M
authors.lastname: Mohana
authors.affiliation: School of Chemistry, Bharthidasan University, Tiruchirappalli 620 024, Tamilnadu, India.
authors.forename: Packianathan Thomas
authors.initials: PT
authors.lastname: Muthiah
authors.affiliation: Department of Chemistry, Clemson University, H.L. Hunter Laboratories, Clemson, SC 29634, USA.
authors.forename: Colin D
authors.initials: CD
authors.lastname: McMillen
keywords: 5-fluorouracil; carboxylic acid dimer; cocrystals; crystal structure; homosynthon; supramolecular heterosynthon; π–π stacking interaction