The origins of the molecular-chiral homogeneity that is the very basis of life remain a tantalizing mystery. Molecular chirality itself is manifest in its interaction with radiation, particularly as optical activity, although an intriguing alternative technique based in X-ray crystallography is being increasingly employed. Thus, X-ray diffraction with anomalous dispersion is currently believed to lead to the absolute configuration of a stereogenic center, the ultimate goal of structural chemistry. However, despite its apparently unerring consistency, the fundamental basis of the anomalous dispersion technique is itself enigmatic. This is because it is unclear how the technique not only distinguishes two enantiomeric lattices but also assigns the absolute configuration: all, apparently, in the absence of an external chiral influence! Indeed, as argued previously, it is highly likely that the technique succeeds because the X-rays employed are circularly polarized, itself a possible consequence of parity violation. All the same, the question of how the absolute configuration is assigned remains, as the chiral sense of the putative circular polarization of the X-rays is unknown. It is argued herein that the anomalous dispersion method is essentially based in the chirality of X-rays that must have entered–although unbeknownst as such–into the calculations leading to the absolute configuration. In fact, the enigma surrounding the anomalous dispersion method derives from uncertainties concerning the theory of X-ray diffraction itself, thus leading to the apparently inescapable conclusion that both methods are essentially empirical — but without detracting from the brilliance of the scientific achievements that led to these methods.
Selenium derivatization and crystallization of DNA and RNA oligonucleotides for X-ray crystallography using multiple anomalous dispersion
