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

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), L-tartaric 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.

Automated summary

This work successfully prepared a series of cocrystals of the modified nucleobase 1-ethyluracil with different coformers and investigated the influence of hydroxyl substituents on cocrystal formation. Characterization and computational studies revealed the structural motifs and energies associated with H-bonding interactions in the cocrystals.