Clindamycin Phosphate-Mediated Enantioseparation of Amino Acids by Capillary Electrophoresis: Molecular Modeling and NMR Insights into the Chiral Recognition Mechanism
- 1Department of Chemistry, Turabah University College, Taif University, Taif 21944, Saudi Arabia
- 2Department of Chemistry, College of Science, King Faisal University, Al-Ahsa 31982, Saudi Arabia
- 3Department of Chemistry, Faculty of Science Al-Zulfi, Majmaah University, Al-Zulfi 11952, Saudi Arabia
Abstract
In this research paper, chiral separation of three amino acids (AAs), namely, tryptophan (Trp), tyrosine (Tyr), and phenylalanine (Phe), was achieved by capillary electrophoresis with clindamycin phosphate as the chiral selector. Factors affecting the chiral separation, such as the BGE pH, concentration of clindamycin, organic modifier concentration, capillary temperature and applied voltage, were optimized and discussed. A BGE consisting of 80 mM clindamycin phosphate and 40 mM borate at pH 7.6 with 30% methanol was found suitable for chiral separation of tryptophan and tyrosine while the same BGE at pH 7.3 was suitable for enantioseparation of phenylalanine. The optimum capillary temperature and applied voltage were 20 °C and 19 kV. Molecular docking (Glide SP/MM-GBSA) and 1H NMR chemical-shift perturbation (CSP) analysis were combined to clarify the chiral recognition of tryptophan, phenylalanine, and tyrosine by clindamycin phosphate. Docking results support clear stereochemical discrimination for Trp, weaker discrimination for Phe, and near-degenerate discrimination for Tyr, and revealed that electrostatic attraction discrimination was the main binding anchor, supported by hydrophobic contacts and hydrogen bonding. The NMR results revealed chemical-shift perturbations and line-broadening patterns consistent with changes in the local chemical environments of clindamycin phosphate regions implicated by the docking models. Pronounced signal broadening in DL-Tyr further revealed dynamic binding behavior that could not be detected by docking alone.
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BibTeX
@article{khalid2026clindamycin,
title = {{Clindamycin Phosphate-Mediated Enantioseparation of Amino Acids by Capillary Electrophoresis: Molecular Modeling and NMR Insights into the Chiral Recognition Mechanism}},
author = {Mohammed A. A. Khalid and Abdalla A. Elbashir and Munirah A. Alfarhan and Shazalia Mahmoud Ahmed Ali},
journal = {Molecules},
year = {2026},
month = oct,
doi = {10.3390/molecules31203580},
url = {https://www.mdpi.com/1420-3049/31/20/3580},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Clindamycin Phosphate-Mediated Enantioseparation of Amino Acids by Capillary Electrophoresis: Molecular Modeling and NMR Insights into the Chiral Recognition Mechanism
AU - Mohammed A. A. Khalid
AU - Abdalla A. Elbashir
AU - Munirah A. Alfarhan
AU - Shazalia Mahmoud Ahmed Ali
PY - 2026
DA - 2026/10/01
JO - Molecules
DO - 10.3390/molecules31203580
UR - https://www.mdpi.com/1420-3049/31/20/3580
AB - In this research paper, chiral separation of three amino acids (AAs), namely, tryptophan (Trp), tyrosine (Tyr), and phenylalanine (Phe), was achieved by capillary electrophoresis with clindamycin phosphate as the chiral selector. Factors affecting the chiral separation, such as the BGE pH, concentration of clindamycin, organic modifier concentration, capillary temperature and applied voltage, were optimized and discussed. A BGE consisting of 80 mM clindamycin phosphate and 40 mM borate at pH 7.6 with 30% methanol was found suitable for chiral separation of tryptophan and tyrosine while the same BGE at pH 7.3 was suitable for enantioseparation of phenylalanine. The optimum capillary temperature and applied voltage were 20 °C and 19 kV. Molecular docking (Glide SP/MM-GBSA) and 1H NMR chemical-shift perturbation (CSP) analysis were combined to clarify the chiral recognition of tryptophan, phenylalanine, and tyrosine by clindamycin phosphate. Docking results support clear stereochemical discrimination for Trp, weaker discrimination for Phe, and near-degenerate discrimination for Tyr, and revealed that electrostatic attraction discrimination was the main binding anchor, supported by hydrophobic contacts and hydrogen bonding. The NMR results revealed chemical-shift perturbations and line-broadening patterns consistent with changes in the local chemical environments of clindamycin phosphate regions implicated by the docking models. Pronounced signal broadening in DL-Tyr further revealed dynamic binding behavior that could not be detected by docking alone.
SN - 1420-3049
ER -