Tetrel and Pnictogen Bonds Complement Hydrogen and Halogen Bonds in Framing the Interactional Landscape of Barbituric Acids

Vijith Kumar,Jane S Murray,Peter Politzer,Giancarlo Terraneo,Patrick Scilabra,Giuseppe Resnati,Francisco Fernandez-Palacio,Andrea Daolio

doi:10.1021/acs.cgd.0c01429

Vijith Kumar, Jane S Murray + Show 6 more

Open Access

https://doi.org/10.1021/acs.cgd.0c01429

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Abstract

Experimental and theoretical studies of fluoro-, chloro-, and bromo-substituted derivatives of barbituric acid and indandione show that imide protons form short hydrogen bonds and bromine or, to a lesser extent, chlorine atoms form halogen bonds. The imide nitrogen atoms act as effective pnictogen bond donors, while C(sp2) and C(sp3) atoms act as tetrel bond donors; the resulting N···O and C···O close interactions are a distinctive feature of crystal lattices in all compounds. Importantly, halogen atoms promote the electrophilicity of C(sp3) sites and favor the formation of C(sp3)···O close contacts. Oxygen atoms of carbonyl groups of barbituric and indandione units or of water molecules function as the interaction acceptor sites: namely, they donate electron density to hydrogen, halogen, nitrogen, and carbon atoms. Modeling of various barbituric acid derivatives indicates that the positive electrostatic potentials of π-holes orthogonal to the C(sp2) carbons and σ-holes on the elongation of quasi-axial F/Cl/Br–C(sp3) bonds merge to produce a single well-defined point of the most positive electrostatic potential on one face of the barbituric acids. This single local maximum of the potential on the molecular face is close to the site occupied by the oxygen forming the C(sp3)···O, and C(sp2)···O, short contacts observed in crystals.

Highlights

An in-depth understanding of supramolecular interactions and their role in driving or affecting molecular recognition phenomena is crucial in diversified fields of chemistry and biology, ranging from the photophysical properties of lightemitting diodes to structure-based drug design.[1,2] Since carbon atoms are ubiquitous in organic compounds, the elucidation of short contacts involving carbon moieties is of paramount importance.Covalently bonded atoms of groups 13−18 of the Periodic Table commonly have anisotropic distributions of electronic density
The results that we have reported provide experimental and computational evidence that C(sp2) and C(sp3) sites can systematically function as tetrel bond (TtB) donors and give rise to close contacts with oxygen atoms in crystalline solids
It is proven that the tendency of C(sp3) atoms of some organic derivatives to function as TtB donors is strong enough to influence the packing of the compounds in crystals: namely, to affect the preferred conformation and/or the network of intermolecular interactions in the crystal lattices

Summary

■ INTRODUCTION

An in-depth understanding of supramolecular interactions and their role in driving or affecting molecular recognition phenomena is crucial in diversified fields of chemistry and biology, ranging from the photophysical properties of lightemitting diodes to structure-based drug design.[1,2] Since carbon atoms are ubiquitous in organic compounds, the elucidation of short contacts involving carbon moieties is of paramount importance. This paper describes the single-crystal Xray structures of barbituric acid derivatives 1a−m, which feature both C(sp2)···O and C(sp3)···O close contacts[49−52] wherein carbon and oxygen atoms serve as electrophilic and nucleophilic sites, respectively. Modeling of these derivatives 1 brings out an unusual and interesting point. It has been frequently considered that C(sp3)···nucleophile contacts may result from or be associated with the formation of hydrogen bonds (HBs) involving the partially positive hydrogen atoms bound to the carbon atom.[38,44] The C(sp3) atom forming the close C(sp3)···O contacts in barbituric derivatives 1 bears no hydrogen atoms; the observed close C···O separations confirm the inherent tendency of C(sp3) atoms bearing electron-withdrawing groups to function as TtB donor sites in the absence of “auxiliary” HBs.

■ RESULTS AND DISCUSSION

■ CONCLUSIONS

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