Determination of absolute structure using Bayesian statistics on Bijvoet differences

Abstract

A new probabilistic approach is introduced for the determination of the absolute structure of a compound which is known to be enantiopure based on Bijvoet-pair intensity differences. The new method provides relative probabilities for different models of the chiral composition of the structure. The outcome of this type of analysis can also be cast in the form of a new value, along with associated standard uncertainty, that resembles the value of the well known Flack x parameter. The standard uncertainty we obtain is often about half of the standard uncertainty in the value of the Flack x parameter. The proposed formalism is suited in particular to absolute configuration determination from diffraction data of biologically active (pharmaceutical) compounds where the strongest resonant scattering signal often comes from oxygen. It is shown that a reliable absolute configuration assignment in such cases can be made on the basis of Cu Kα data, and in some cases even with carefully measured Mo Kα data.