Structural, spectral, theoretical and anticancer studies on new co-crystal of the drug 5-fluorouracil

Abstract New co-crystal containing 5-Fluorouracil (an anticancer drug) as an active pharmaceutical ingredient (API) was prepared by the liquid-assisted grinding method. The prepared co-crystal namely, 5-fluorouracil hydroquinone (5FUHYQ) was studied through single X-ray diffraction. It reveals that the crystal packing is supported by N H⋯O and O H⋯O classical hydrogen bonds forming a sheet-like molecular architecture. The drug molecules are connected themselves through three N H⋯O intermolecular hydrogen bonds leading to two dimeric ring R 2 2 (8) motifs. These two ring motifs are placed adjacently forming two chain C 2 1 (6) motifs which are running along the a -axis of the unit cell, oppositely. The drug molecules are sandwiched at y  = 1/2 and the coformers are placed at y  = 0 and 1 making the supramolecular assembly. These ring and chain motifs to form a hydrogen-bonded sheeted. The supramolecular sheets are parallel to ( 0 4 2 ¯ ) and ( 0 4 ¯ 2 ) planes of the unit cell. This molecular aggregation is replicated in the diffraction pattern as a strong intensity X-ray peaks. The 5FUHYQ has lower calculated density than the parent drug which favour the improved membrane permeability of the drug. Geometrical optimizations of the compound were done by Hartree-Fock (HF) and Density Functional Theory (DFT) using the B3LYP function with the 6-311++G(d,p) basis sets. The optimized molecular geometries and computed vibrational spectra are compared with their experimental counterparts. The Frontier Molecular Orbital (FMO) analysis shows that the present compound has lower band gap value which reiterates the possible pharmaceutical activity of the compound. The anticancer activity of the parent drug is retained against human cervical cancer cell line (HeLa) in this new co-crystalline form.