Uracil Derivatives for Halogen-Bonded Cocrystals.

Mónica Benito,Yannick Roselló,Antonio Frontera,Miquel Barceló-Oliver,Elies Molins

doi:10.3390/ijms221910663

Abstract

Among non-covalent interactions, halogen bonding is emerging as a new powerful tool for supramolecular self-assembly. Here, along with a green and effective method, we report three new halogen-bonded cocrystals containing uracil derivatives and 1,2,4,5-tetrafluoro-3,6-diiodobenzene as X-bond donor coformer. These multicomponent solids were prepared both by solvent-drop grinding and solution methods and further characterized by powder and single-crystal X-ray diffraction, Fourier-transformed infrared spectroscopy, and thermal methods (TGA-DSC). In order to study the relative importance of hydrogen versus halogen bonds in the crystal packing, computational methods were applied.

Highlights

Barceló-Oliver, M.; Frontera, A.; In 2013, after several years working on the rationalization and unification of interactions involving halogens, the IUPAC defined the halogen bond as a non-covalent interaction when there is evidence of a net attractive interaction between an electrophilic region associated with a halogen atom in a molecular entity and a nucleophilic region in another, or the same, molecular entity [1]
We reported thewe preparation the mechanochemical method of a reported using the preparation using the mechanochemical met halogen bondedofcocrystal based on
Asfrom stated from the supramolecular all the nucleobases tial groups for forming non-covalent interactions such as hydrogen bonds or π–π stacking tential groups for forming non-covalent interactions such as hydrogen bonds or interactions

Summary

Introduction

Barceló-Oliver, M.; Frontera, A.; In 2013, after several years working on the rationalization and unification of interactions involving halogens, the IUPAC defined the halogen bond as a non-covalent interaction when there is evidence of a net attractive interaction between an electrophilic region associated with a halogen atom in a molecular entity and a nucleophilic region in another, or the same, molecular entity [1].Over the last decades, the use of this non-covalent interaction has grown rapidly as shown by several reviews [2,3,4,5]. A plethora of opportunities in areas such as organic chemistry [4], supramolecular chemistry [5], crystal engineering including pharmaceutical cocrystals [6,7,8,9,10,11], polymer science [12,13], medicinal chemistry, and chemical biology [14,15,16,17,18] have grown, taking advantage of its high linear directionality, tunable bonding strength, hydrophobicity, or the size of the halogen atom. Alkylated nucleobases represent important models for explaining the contribution of DNA methylation in gene expression through its regulation or inhibition [22]. For this reason, an increased effort from experimental and theoretical points of view is necessary for understanding this type of non-covalent interaction, in many cases with a similar strength to hydrogen bonds

Methods

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Discussion

Conclusion