Weak Intermolecular Interactions in a Series of Bioactive Oxazoles.

Anita M Grześkiewicz,Tomasz Stefański,Maciej Kubicki

doi:10.3390/molecules26103024

Anita M Grześkiewicz, Tomasz Stefański + Show 1 more

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https://doi.org/10.3390/molecules26103024

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Abstract

The intermolecular interactions in a series of nine similar 4,5-phenyl-oxazoles were studied on the basis of crystal structures determined by X-ray diffraction. The crystal architectures were analyzed for the importance and hierarchies of different, weak intermolecular interactions using three approaches: the geometrical characteristics, topological analysis (for the model based on the transfer of multipolar parameters), and energetics of the molecule–molecule interactions. The geometries of the molecules were quite similar and close to the typical values. The results of the analysis of the interactions suggest that the number of nonspecific interactions is more important than the apparent strength of the specific interactions. The interactions involving covalently bound bromine and divalent sulfur atoms were classified as secondary, they certainly did not define the crystal packing, and they played a minor role in the overall crystal cohesion energies. Incidentally, another method for confirming the degree of isostructurality, according to the topologies of the interactions, is described.

Highlights

Intermolecular interactions constitute principal factors in molecular recognition and, as a consequence, biological activity
The situation seems to be especially profitable if there is a series of similar compounds available, when small differences in the molecular structure may be related to significant changes in crystal architectures, i.e., supramolecules par excellence
From the classical hydrogen bonds of, for instance, the O–H···O=C type, through weaker interactions involving hydrogen atoms, halogen, chalcogen, pnicogen, and tetrel interactions, or π···π, cation···π, and anion···π interactions, to quite exotic ones, such as hydrogen···hydrogen, there are several scholars dealing with these phenomena in the literature (e.g., [4,5,6,7,8])

Summary

Introduction

Intermolecular interactions (specific, such as hydrogen bonds, or nonspecific, such as van der Waals interactions) constitute principal factors in molecular recognition and, as a consequence, biological activity. Dunitz and Gavezzotti [9] started a relevant discussion on the role and importance of intermolecular specific interactions of the types listed above (with the notable exception of the classical, strong hydrogen bonds) for crystal architecture with respect to the more diffuse, delocalized interactions between the molecular electron density distributions. They posited that “one cannot deny that these weak intermolecular atom–atom bonds can be neatly categorized on the basis of geometrical, spectroscopic, and even energetic criteria The question is not whether weak hydrogen bonds ‘exist’, but rather to what extent are they relevant in distinguishing one possible crystal structure from another?” This discussion has been continued (see, for instance, the exchange in IUCrJ in 2015 [10,11,12])

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