Site Selectivity of Halogen Oxygen Bonding in 5- and 6-Haloderivatives of Uracil

Portalone Portalone

doi:10.3390/cryst9090467

Abstract

Seven 5-and 6-halogenated derivatives of uracil or 1-methyluracil (halogen = Cl, Br, I) were studied by single crystal X-ray diffraction. In contrast with pure 5-halouracils, where the presence of N-H…O and C-H…O hydrogen bonds prevents the formation of other intermolecular interactions, the general ability of pyrimidine nucleobases to provide electron donating groups to halogen bonding was confirmed in three crystals and cocrystals containing uracil with the halogen atom at the C6 position. In the latter compounds, among the two nucleophilic oxygen atoms in the C=O moiety, only the urea carbonyl oxygen O1 can act as halogen bond acceptor, being not saturated by conventional hydrogen bonds. The halogen bonds in pure 6-halouracils are all rather weak, as supported by Hirshfeld surface analysis. The strongest interaction was found in the structure of 6-iodouracil, which displayed the largest (13%) reduction of the sum of van der Waals (vdW) radii for the contact atoms. Despite this, halogen bonding plays a role in determining the crystal packing of 6-halouracils, acting alongside conventional hydrogen bonds.

Highlights

Over the past two decades, it has been well recognized that the diversity of non-covalent interactions involving halogen compounds are topical in biology, materials science, and crystal engineering [1,2]
Halogen bonding plays a role in determining the crystal packing of 6-halouracils, acting alongside conventional hydrogen bonds
The purpose of this study was to ascertain the existence and the preferred donor and acceptor sites of halogen bonds (C-O· · · X) in the presence of hydrogen bonds in pure pyrimidine nucleobases halosubstituted at the 5- and 6-position

Summary

Introduction

Over the past two decades, it has been well recognized that the diversity of non-covalent interactions involving halogen compounds are topical in biology, materials science, and crystal engineering [1,2]. Hydrogen bonding (HB) is commonly the predominant interaction, the biological significance of halogen bonding (XB) has been widely demonstrated [3]. XB is a stabilizing directional interaction due to an attraction between the positively charged area of a covalently bound halogen atom and an electron donor species. As the halogen polarizability is the key factor in XB, the strength of the halogen bonding is expected to decrease in the order I > Br >. Several examples of XB have been culled from a comprehensive survey of halogenated protein and nucleic acid structures in the Protein Data Bank. It has been shown that an unusually strong Br···O intermolecular contact, 2.7 Å, i.e., 0.8 times the sum of van der Waals (vdW)

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