1-Ethyluracil, a New Scaffold for Preparing Multicomponent Forms: Synthesis, Characterization, and Computational Studies

Abstract

In this work, we describe the successful preparation of a series of cocrystals of the modified nucleobase 1-ethyluracil with different coformers in a 1:1 or 2:1 (nucleobase:coformer) ratio including urea (URE) or some compounds containing carboxylic and hydroxyl groups such as L-malic acid (MAL), Ltartaric acid (TAR), 2-hydroxybenzoic acid (SAL), 4-hydroxybenzoic acid (4HB), and 2,4-dihydroxybenzoic acid (DHB). The influence of the hydroxyl substituent on the alkyl chain for 1•TAR and 1•SAL cocrystals or the phenyl ring for 1•SAL, 1•4HB, and 1• DHB multicomponent solids was studied. All of the compounds were characterized by powder X-ray diffraction, FT-IR, and thermal methods. Moreover, for those whose single-crystal structures could be determined, computational studies were also performed to investigate the factors that may affect the cocrystal formation, the recurrent motifs, and the energies associated with the H-bonding interactions using DFT calculations and a combination of the quantum theory of atoms in molecules (QTAIM) and the noncovalent interaction index (NCIplot) computational tools.

Uracil Derivatives for Halogen-Bonded Cocrystals

“…Thymine and 5-fluorouracil were obtained from commercial suppliers and used without further purification. 1-Ethyluracil was prepared following a modified synthesis reported previously [34]. TFDIB was purchased from Cymit Química S.L.…”

Methylxanthines for halogen bonded cocrystals with 1,4-diiodotetrafluorobenzene: green synthesis, structure, photophysics and DFT studies

“…7,8 In the last few years, some of us have studied the propensity of different modified nucleobases for the preparation of multicomponent solids (salts and cocrystals) containing both hydrogen and halogen bonds. [9][10][11][12] Now we study xanthines, which are indeed purine-based nitrogen compounds with a structure similar to that of DNA bases adenine and guanine and their related nucleotides. This even makes them important scaffolds for the exploration of new potential drugs.…”

Polymorphism and Multi-Component Crystal Formation of GABA and Gabapentin

“…Even Density Functional Theory (DFT)-based programs like Giannozzi's Quantum Espresso (QE) or the popular Gaussian software show increased usage and performance [19,20]. Recent advancements in computational crystal structure evaluations allow insights into the basics of the crystallization process [21][22][23][24] and in-depth studies specifically aimed to describe properties of singular compounds of interest [25][26][27][28].…”