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.

This work has been carried out through MINECO/FEDER grant ENE2015-63969. M.B. and E.M. are grateful to the Severo Ochoa FunFuture project (MICINN, CEX2019-917S) and the Generalitat de Catalunya (2017SGR1687). M.B.-O. thanks the Vice-Rector for Research and International Relations of the University of the Balearic Islands for financial support in setting up the single-crystal X-ray diffraction facility. A.F. thanks the MICIU/AEI from Spain for financial support (Project CTQ2017-85821-R, Feder funds).

Peer reviewed