Chiral discrimination in the formation of diastereomeric pairs. A thermodynamic and conformational investigation

Abstract

Chiral discrimination in the formation of diastereomeric adducts between L-(+)-ascorbic acid and enantiomeric α-helical polypeptides carrying Fe^III complex ions has been investigated by microcalorimetric measurements (25 °C) as well as by theoretical conformational analysis. Stereoselectivity in the binding results from a complex interplay of ionic and non-bonded interactions that ultimately leads to modest effects, in full agreement with experimental data. These results are consistent with those obtained earlier by using L-dopa (L-dihydroxyphenyl-alanine) and L-adrenaline as substrates. The diastereomeric complexes were also found to undergo an intramolecular electron transfer from the substrate to the central metal ion with a kinetic stereoselectivity definitely higher than the thermodynamic one. Both these effects and the lack of stereoselectivity in the formation of the association complexes with L-cysteine are discussed in the light of the relationship between chiral discrimination and modes of binding of asymmetric species. A statistical analysis is reported, suggesting that efficiency in chiral recognition and discrimination demands sterically constrained species in that conformational rigidity enhances steric differences between the diastereomeric pairs.