Could linear solvation energy relationships give insights into chiral recognition mechanisms?

Abstract

Five parameter linear solvation energy relationships (LSER) are known to have little or no shape recognition ability. However, it is proposed to use LSER studies to get insights into chiral recognition mechanisms. Since the two enantiomers have exactly the same five A-V solute descriptors being still separated by chiral stationary phases (CSPs), it can be considered that they form two different transient diastereoisomers with the CSP. It is then possible to perform LSER studies on the enantioselectivity factors taken as the two enantiomer retention factor ratios. In a first step, the five a-v system parameters of four CSPs of the macrocyclic glycopeptide types were determined using a set of test solutes with known A-V descriptors, both in the reversed phase and the normal phase modes. In a second step, the A-V descriptors of 18 enantiomeric pairs were tentatively established using five achiral columns with known a-v parameters. This was successful for the five molecular enantiomers only. It was found that the predicted retention factor for the molecular enantiomers separated on a given CSP corresponded either to retention factor of the first experimentally eluted enantiomer or to the second one or to none of them. Using the enantioselectivity factors it was possible to obtain the Δa-Δv parameters corresponding to the difference in CSP properties seen by the two enantiomers. For the five molecular enantiomeric pairs in the reversed phase mode with a teicoplanin CSP, it was found that there was an elevated contribution by the e coefficient that we interpret as a possible interaction between surface charges on the teicoplanin CSP and solute induced dipoles. Steric effects, seen on the v parameter, are second in magnitude followed by H-bond and polar interactions. Only one solute could be studied in the normal phase mode showing a different mechanism with polar and steric major interactions.

An insight into the use of dimethylphenyl carbamate cyclofructan 7 chiral stationary phase in supercritical fluid chromatography: The basic comparison with HPLC

“…The v coefficient describing dispersion interactions represents the most important interaction that leads to decrease of retention in both separation systems. Negative values of the term v are typical for a normal phase mode . Higher absolute values of the v coefficient in SFC indicates that the mobile phase participates in dispersion interactions with the solute to a greater extent in SFC than in HPLC.…”

“…The linear free energy relationship model (LFER) is an effective tool for qualitative and quantitative characterization of interactions participating in the retention mechanism (e.g. ). However, it must be understood that not all interactions that lead to retention can lead to chiral 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

“…To define the groups of solutes sharing a common enantiorecognition mechanism, we adopted a procedure first suggested by Mitchell et al [12], who investigated chiral recognition mechanisms on macrocyclic glycopeptide CSPs using HPLC. Our study used a much larger number of racemates so that the conclusion based on a better data set would be more substantiated.…”

“…Recent studies of Mitchell et al [12,13] showed that the solvation parameter model [14] can provide relevant information about the interactions contributing to retention and enantioselective separation on different macrocyclic glycopeptide and immobilized polysaccharide-based CSPs in HPLC.…”

Development of New HPLC Chiral Stationary Phases Based on Native and Derivatized Cyclofructans

“…polysaccharide-based CSPs, [2][3][4][5][6][7][8][9][10][11] macrocyclic antibiotic CSPs, [12][13][14][15][16][17][18][19][20][21][22] and π complex CSPs. [23][24][25][26] Researchers continue to make great efforts to develop new HPLC CSPs, which could make a substantial impact on enantiomeric separations.…”