γ-cyclodextrin based metal organic frameworks as micellar electrokinetic chromatography additive for the chiral...

A strategy utilizing oriented γ-cyclodextrin-based metal organic frameworks (γ-CD-MOFs) as chiral additives in micellar electrokinetic chromatography (MEKC) is presented for enhanced enantioseparation of dansylated D,L-amino acids (Dns-D,L-AAs). Its core innovation resides in the fixed orientation of γ-CD within the MOFs structure. This unique characteristic facilitates a shift in chiral recognition from "random interactions" to a "directional and highly efficient recognition" process, thereby substantially enhancing the resolution of chiral separation while overcoming the limitations of free γ-CD, including unstable interactions and poor reproducibility. Systematic optimization of SDS concentration (9.0 mM), γ-CD-MOFs concentration (16.0 mM), and buffer pH (9.5) yielded a maximum resolution (R_s) of 2.2, representing a 50 % improvement over traditional γ-CD. Under these conditions, 14 pairs of Dns-D,L-AAs achieved baseline separation, with 4 additional pairs showing partial separation. Quantitative validation for D,L-methionine (D,L-Met) demonstrated excellent linearity (19.8-1500 μM, r² = 0.999), low limits of detection (6.6 μM) and quantitation (19.8 μM), and high stability (relative standard deviations <5 %). Application to rat plasma samples revealed peak concentration (C_max) of D,L-Met at 90 min post-injection, highlighting its utility in pharmacokinetic studies of amino acid-derived prodrugs (e.g., S-adenosylmethionine). This work introduces oriented γ-CD-MOFs as a transformative chiral additive in MEKC, offering superior selectivity and reproducibility for pharmaceutical and biomedical analyses.