Probability rule for chiral recognition

Abstract

Molecular Chirality is of central interest in biological studies because enantiomeric compounds, while indistinguishable by most inanimate systems, show profoundly different properties in biochemical environments. Enantioselective separation methods, based on the differential recognition of two optical isomers by a chiral selector, have been amply documented. Also, great effort has been directed towards a theoretical understanding of the fundamental mechanisms underlying the chiral recognition process. Here we report a comprehensive data examination of enantio separation measurements for over 72000 chiral selector-select and pairs from the chiral selection compendium CHIRBASE. The distribution of alpha = k'(D)/k'(L) values was found to follow a power law, equivalent to an exponential decay for chiral differential free energies. This observation is experimentally relevant in terms of the number of different individual or combinatorial selectors that need to be screened in order to observe alpha values higher than a preset minimum. A string model for enantiorecognition (SMED) formalism is proposed to account for this observation on the basis of an extended Ogston three-point interaction model. Partially overlapping molecular interaction domains are analyzed in terms of a string complementarity model for ligand-receptor complementarity. The results suggest that chiral selection statistics may be interpreted in terms of more general concepts related to biomolecular recognition.

Insights into chiral recognition mechanisms in supercritical fluid chromatography. II. Factors contributing to enantiomer separation on tris-(3,5-dimethylphenylcarbamate) of amylose and cellulose stationary phases

“…Another way of formulating this idea is that strong retention is not necessarily associated to high enantioselectivity, and vice versa. This was confirmed by studies from Kafri and Lancet [21] who reported a comprehensive data examination of enantioseparation mea- surements for over 72,000 chiral separations and concluded that no correlation existed between retention factors and separation factors. Thus, while some features are common to ADMPC and CDMPC (E, A and F essentially), others (S, B, V and G) clearly have different influences on the enantiorecognition capability of the two CSPs.…”

Review of aqueous chiral electrokinetic chromatography (EKC) with an emphasis on chiral microemulsion EKC

“…Mathematical models for optimizing chiral selector conditions with CDs have been developed by Wren and Rowe [30][31][32][33]. Kafri and Lancet [34] examined chromatographic data and proposed the string model for enantiorecognition (SMED). Their goal was to provide guidelines for selection of a chiral agent to reduce the screening process.…”

Exploring enantioselective molecular recognition mechanisms with chemoinformatic techniques

“…In a quantitative form also Del Rio and Gasteiger [147] applied this idea to devise a simple method based on the atomic counts around the chiral centre to assess whether a compound will be separated or not on a Whelk-O1 CSP. An interesting study by Kafri and Lancet [134] reported a probability rule for chiral recognition in which the authors critically discussed the three-point interaction model and depicted a more realistic representation of the molecular contacts that might mediate chiral recognition in terms of large number of elementary interactions. In fact, despite the strictly geometric idea behind the three-point interaction model would allow one to describe the minimum requirement for the enantioselective recognition, many of the abovementioned chemoinformatic studies as well as molecular modelling calculations show that the chiral discrimination occurs with a complexity of mechanisms even when relatively simple CSPs are considered [10,134,164,165].…”