Virtual issue on absolute structure

Abstract

It should come as no surprise, following after the first virtual issue on polymorphism (http://journals.iucr.org/special_issues/2011/polymorphism/), that the Editor has chosen absolute structure (http://journals.iucr.org/special_issues/2012/absolutestructure/) as the topic for this year's effort. The unambiguous determination of absolute structure, particularly where the absolute configuration of an enantiomerically pure chiral molecule is needed, is important not only for synthetic and natural-product chemists, who wish to fully characterize their products, but can be a critical step for the pharmaceutical industry, where opposite enantiomers of a drug can have quite different biological properties. One should also mention those crystal engineers endeavouring to prepare non-centrosymmetric crystals for applications such as second-harmonic generation.A major impetus in enabling the study of absolute structure has been the advent of dual radiation CCD diffractometers. This means that more laboratories have routine access to Cu K radiation with the potential to successfully study light-atom structures. The latter have been viewed as one of the remaining difficulties in this field. This virtual issue has the ambition to present the results of crystal-structure determinations which demonstrate new successes and remaining limitations in absolute-structure evaluation.Historically, the determination of absolute structure started on the wrong foot with Friedel (1913) who, by a false argument using optics and crystal symmetry, managed to prove that the intensities of the reflections hkl and hkl are always identical, regardless of the point group of the crystal. The effects of this unfortunate mistake are still felt today in the teaching of diffraction by crystals, as Friedel's Law is often presented and used as a fundamental principle whereas it is no more than an approximation, which often does not need to be invoked. Resonant scattering was predicted theoretically by Waller (1928). The first determination of absolute structure by X-ray diffraction appeared as a byproduct of a carefully contrived experiment by Coster et al. (1930) to demonstrate the existence of resonant scattering. Coster et al. (1930) used a crystal of hexagonal ZnS (zincblende), which is non-centrosymmetric and achiral, in an experiment with Au L radiation. The latter has a wavelength corresponding to the K absorption edge of Zn which falls between the Au L 1 and Au L 2 lines. The first chemical application of absolute-structure determination by X-ray diffraction was published by Peerdeman et al. (1951) and Bijvoet et al. (1951). They deduced the absolute configuration of the (2R,3R)-tartrate anion in its Na Rb salt. The modern developments of absolute-structure determination by least-squares refinement find their source in a paper by Rogers (1981). In 1984, Jones coined the term absolute structure. Your editorialist has published extensively in this field starting with the oft-quoted paper of Flack (1983).One has no choice in this editorial but to m...

Use of intensity quotients and differences in absolute structure refinement

“…Analysis of non-centrosymmetric crystal structures published in Acta Cryst. C in 2007, 2011 and 2012 has shown that even the intensity data of structures with large Friedif stat values may be entirely dominated by random uncertainties and systematic errors (Flack, 2012;Flack et al, 2011).…”

Ethyl (3S)-3-[(3aR,5R,6S,6aR)-6-hydroxy-2,2-dimethyltetrahydrofuro[4,5-d][1,3]dioxol-5-yl]-3-{(3S)-3-[(3aR,5R,6S,6aR)-6-hydroxy-2,2-dimethyltetrahydrofuro[4,5-d][1,3]dioxol-5-yl]-5-oxoisoxazolidin-2-yl}propanoate chloroform monosolvate

“…On a broader front, it is worth reminding that the standard uncertainty in the Flack parameter, u(x), is the key to its correct interpretation (Flack & Bernardinelli, 2000;Thompson & Watkin, 2009). The use of 2AD plots is thus strongly advised for the validation of absolute-structure determinations (Flack, 2012), together with Flack x and Hooft y parameters. Unfortunately, these plots are not yet used on a routine basis in chemical crystallography.…”

A Holistic Approach to Determining Stereochemistry of Potential Pharmaceuticals by Circular Dichroism with β-Lactams as Test Cases

“…However, the primary requirement for its use is to have a properly diffractive crystal, which cannot always be fulfilled. Even with suitable crystals, examples of incorrect absolute configuration determination based on X-ray crystallography alone or crystallographic results needing support by other methods can quite often be found in the literature [ 4 , 5 , 6 , 7 ]. One of the reasons may be more ready crystallization of an unrepresentative component of the bulk material [ 8 ].…”