Self-induced recognition of enantiomers (SIRE) and its application in chiral NMR analysis

Potentially Mistaking Enantiomers for Different Compounds Due to the Self-Induced Diastereomeric Anisochronism (SIDA) Phenomenon

“…We hope that this study presents a warning to practitioners to be on the lookout for the occurrence of SIDA in their own research and the problems it can cause, namely confusion, misidentification, and incorrect evaluation of purity, and thus caution is advised and care should be duly exercised when analyzing chiral compounds that are likely to form associates in solution with respect to the prevailing conditions, particularly the concentrations of the analytes. However, SIDA also represents an opportunity to be taken advantage of, e.g., the determination of the ee becomes simple when conditions are right [1,3]. Furthermore, with the occurrence of SIDA, one may consider if unconventional enantiopurification methods, such as SDE via chromatography, could be applicable as the two phenomena often occur together.…”

“…Since the formation constant for the association of homochiral molecules (K hom ), i.e., R with R or S with S, is likely to be different to the formation constant for the association of (KHOM), i.e., R with R or S with S, is likely to be different to the formation constant for the association of heterochiral molecules (KHET), the positions of the two equilibria will likely be different. The observed chemical shift (δobs) of a nucleus is therefore the population-weighted average of the δ's of the nucleus in the three states SM, HOM, and HET [1,2]. Furthermore, as the equilibrium shifts with a change in conditions (e.g., concentration), the contributions of the δ's from the SM, HOM, and HET states to the population-weighted average δ alter accordingly.…”

“…Furthermore, as the equilibrium shifts with a change in conditions (e.g., concentration), the contributions of the δ's from the SM, HOM, and HET states to the population-weighted average δ alter accordingly. Due to these dynamic effects, enantiopure and racemic solutions can exhibit distinct spectra, and even distinct signals for the two enantiomers can result in the case of scalemates [1,3]. The SIDA phenomenon has recently been well reviewed [1] and a deeper explanation of SIDA is provided in Appendix A.…”

“…Due to these dynamic effects, enantiopure and racemic solutions can exhibit distinct spectra, and even distinct signals for the two enantiomers can result in the case of scalemates [1,3]. The SIDA phenomenon has recently been well reviewed [1] and a deeper explanation of SIDA is provided in Appendix A. The dynamic equilibria of a chiral compound that forms homo-(HOM) and heterochiral (HET) associates will yield different distributions of the enantiomers between the various associates depending on their concentrations and the values of KHOM and KHET.…”

“…The transitory associates formed in solution may consist of dimeric or higher-order oligomeric associates of variable size, but are depicted here only as dimers for clarity. Due to dissimilar δ's for SM, HOM, and HET, enantiopure and racemic solutions can thus present distinct spectra, and even distinct signals for the two enantiomers can result in the case of scalemates [1,3].…”