Mechanism of enantioseparation of DL-pantothenic acid in ligand exchange capillary electrophoresis using a diol-borate system

Borate complexes formed in the ternary system at pH 9.2 containing borate, (S)-3-amino-1,2-propanediol (SAP), and DL-pantothenic acid (DL-PTA) were identified by ¹³C and ¹¹B NMR, and it is confirmed that the binary complexes, [B(OH)₂(SAP)], [B(SAP)₂]⁺ [B(OH)₂(D- or L-PTA)]^2-, and [B(D- or L-PTA)₂]^3- (including [B(D-PTA)(L-PTA)]^3-), and the ternary complexes, [B(SAP)(D- or L-PTA)]^-, coexist at equilibrium in the ternary system. Thermodynamic experiments by variable-temperature ¹¹B NMR revealed that the ternary complex, [B(SAP)(D-PTA)]^-, is entropically more stable than [B(SAP)(L-PTA)]^-. Because two geometrical isomers are possible for the respective ternary complexes, semi-empirical molecular orbital calculations were performed by PM5, PM3, and AM1 methods in order to obtain the optimized structures. It is indicated from the calculated heats of formation and experimentally obtained thermodynamic parameters that the (S)-isomer is more probable for the respective ternary complexes with D- and L-PTA. In the optimized structure of (S)-[B(SAP)(D-PTA)]^- in water, the SAP and D-PTA ligands were oppositely oriented to form a rather linear structure, while the diastereomer, (S)-[B(SAP)(L-PTA)]^-, had a folded structure. Because such a difference in the solvated structure of the ternary complexes can give a different electrophoretic velocity in CE, the enantioseparation Of DL-PTA in CE is reasonably attributed to a difference in the observed electrophoretic mobility for the equilibrated ternary systems containing the respective ternary complexes.