Dynamic ligand‐exchange chiral stationary phase from S‐benzyl‐(R)‐cysteine

Abstract

S-benzyl-(R)-cysteine (R-SBC) is a new chiral ligand-exchange stationary phase which has proved to be effective in the analytical separation of some natural and unnatural underivatized amino acids with fair to good separation and resolution factors. The dynamic coating of the RP-18 solid support with S-Benzyl-(R)-cysteine (R-SBC) gives rise to a stable and efficient chiral stationary phase (CSP) that has been successfully employed. The mechanism of chiral recognition is discussed and a molecular modeling study aimed at identifying molecular descriptors responsible for observed different behaviours of analytes upon different albeit closely related selectors is discussed.

(S)‐(–)‐α,α‐Di(2‐naphthyl)‐2‐pyrrolidinemethanol, a useful tool to study the recognition mechanism in chiral ligand‐exchange chromatography

“…As previously reported [2], the side chain of the amino acid enantiomers can engage intermolecular hydrophobic interac- tions with both the anchor portion of the chiral selector and with the RP-18 carbon chain layers. The extent and geometry of these interactions will determine the elution order.…”

“…While N-substituted amino acids have been largely employed as chiral selectors in CLEC, in view of the strong enantioselectivity effects generated by ligands that contain substituted amino groups with electron donating effects [16,17], we have recently directed our studies and applications toward selectors with free amino acid moiety, thus demanding of a strongly hydrophobic side chain the task to interact and discriminate between the enantiomers [2,24]. Accordingly, S-benzyl-(R)-cysteine (R-SBC) [2] and S-Trityl-(R)-cysteine (R-STC) [24] showed to be new, rather inexpensive chiral selectors endowed with a strong lipophilic character that comes through the combination of the sulphur atom and the aromatic moiety. Both hydrophobically bind to the C-18 carbon chain layer thus producing a stable, dynamically coated chiral stationary phase endowed with good enantiomer recognition ability.…”

“…In the particular case of the mixed, chiral coated stationary phase (MCSP mode), the enantiomer recognition process is mainly the result of, to an extent, the peculiar and selective interaction ability between the portion of the ternary complex containing the analyte and the stationary phase [2]. While N-substituted amino acids have been largely employed as chiral selectors in CLEC, in view of the strong enantioselectivity effects generated by ligands that contain substituted amino groups with electron donating effects [16,17], we have recently directed our studies and applications toward selectors with free amino acid moiety, thus demanding of a strongly hydrophobic side chain the task to interact and discriminate between the enantiomers [2,24]. Accordingly, S-benzyl-(R)-cysteine (R-SBC) [2] and S-Trityl-(R)-cysteine (R-STC) [24] showed to be new, rather inexpensive chiral selectors endowed with a strong lipophilic character that comes through the combination of the sulphur atom and the aromatic moiety.…”

“…Models developed to describe enantioselectivity in CLEC invoke the presence of multicomponent complexes containing a central metal ion (usually Cu 2+ ) chelated by two chiral bifunctional molecules, the selector and the analyte [2]. One or more solvent molecules complete the first solvation sphere of the metal ion.…”

Enantioselective HPLC of potentially CNS‐active acidic amino acids with a cinchona carbamate based chiral stationary phase

“…[1][2][3][4] On the contrary, the enantiomer separation of free amino acids with nonderivatized (nonprotected) amino groups is much more challenging. LC methods of choice for this task make use of teicoplanin or teicoplanin aglycone CSPs (Chirobiotic T and TAG, respectively), [8][9][10][11] chiral ligand exchange chromatography systems, [12][13][14][15] or chiral crown ether CSPs. [16][17][18] Underivatized amino acids endowed with specific physicochemical features such as the presence of an additional ionizable group and/or particularly bulky portions can also be resolved on quinine and quinidine carbamate CSPs (Chiralpak QN-AX and QD-AX, respectively).…”