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Separation of folinic acid diastereomers in capillary electrophoresis using a new cationic β-cyclodextrin derivative.

Yu J, Liang X, Wang Z, Guo X, Sun T, Guo X - PLoS ONE (2015)

Bottom Line: The effect of background electrolyte pH, the concentration of the cyclodextrin additive, and organic modifier on the separation was investigated.A good separation of folinic acid diastereomers was obtained with 30 mmol/L phosphate buffer at pH 6.50 containing 6.0 mmol/L of mono-6-deoxy-6-piperdine-β-cyclodextrin in 10% acetonitrile.Moreover, a computational modeling study, using the semi-empirical PM3 method, was used to discuss the possible mechanism of separation of folinic acid with mono-6-deoxy-6-piperdine-β-cyclodextrin.

View Article: PubMed Central - PubMed

Affiliation: Department of Pharmaceutical Analysis, School of Pharmacy, Shenyang Pharmaceutical University, Ministry of Education, Shenyang, Liaoning Province, P. R. China.

ABSTRACT
A method for the separation of folinic acid diastereomers by capillary electrophoresis in chiral separation media was developed. Aiming to achieve a good separation of the anionic analytes, a newly synthesized cationic β-cyclodextrin derivative, mono-6-deoxy-6-piperdine-β-cyclodextrin, was applied as the chiral selector. The effect of background electrolyte pH, the concentration of the cyclodextrin additive, and organic modifier on the separation was investigated. A good separation of folinic acid diastereomers was obtained with 30 mmol/L phosphate buffer at pH 6.50 containing 6.0 mmol/L of mono-6-deoxy-6-piperdine-β-cyclodextrin in 10% acetonitrile. Based on the capillary electrophoresis data, the binding constants of each diastereomer with mono-6-deoxy-6-piperdine-β-cyclodextrin were determined. Moreover, a computational modeling study, using the semi-empirical PM3 method, was used to discuss the possible mechanism of separation of folinic acid with mono-6-deoxy-6-piperdine-β-cyclodextrin.

No MeSH data available.


Related in: MedlinePlus

The optimized geometries for the lowest energy conformation for the inclusion complexes of folinic acid diastereomers with PIP-β-CD.(A) levo-folinic acid with PIP-β-CD. (B) (6R,2'S)-diastereomer with PIP-β-CD. The molecular electrostatic potential (MEP) maps of the optimized conformation for the inclusion complexes of folinic acid diastereomers with PIP-β-CD. (C) levo-folinic acid with PIP-β-CD. (D) (6R,2'S)-diastereomer with PIP-β-CD.
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pone.0120216.g003: The optimized geometries for the lowest energy conformation for the inclusion complexes of folinic acid diastereomers with PIP-β-CD.(A) levo-folinic acid with PIP-β-CD. (B) (6R,2'S)-diastereomer with PIP-β-CD. The molecular electrostatic potential (MEP) maps of the optimized conformation for the inclusion complexes of folinic acid diastereomers with PIP-β-CD. (C) levo-folinic acid with PIP-β-CD. (D) (6R,2'S)-diastereomer with PIP-β-CD.

Mentions: Firstly, using the optimized structures above, the semi-empirical PM3 method [12] was applied to search for the most stable inclusion complexation of folinic acid diastereomers into PIP-β-CD cavity from its wide (Model I) and narrow (Model II) sides by scanning the coordinate Z, from -8A to 8 A intervals. The calculated binding energies (ΔE) associated with the formation complexes of folinic acid diastereomer with PIP-β-CD are obtained using following equation: ΔE = Ecomplex − (Efree-guest + Efree-host), where Ecomplex, Efree-guest, Efree-host are the energies of complexes of folinic acid diastereomer with PIP-β-CD, free folinic acid diastereomer and free PIP-β-CD, respectively. The difference of ΔE of each isomer with PIP-β-CD is calculated using following equation: ΔΔE = ΔElevo-folinic acid /(PIP-β-CD) − ΔE(6R,2'S)-diastereomer /(PIP-β-CD), where ΔElevo-folinic acid /(PIP-β-CD) means the calculated binding energies of complexes of levo-folinic acid with PIP-β-CD, and ΔE(6R,2'S)-diastereomer /(PIP-β-CD) means the calculated binding energies of complexes of (6R,2'S)-diastereomer with PIP-β-CD. For model I, ΔElevo-folinic acid /(PIP-β-CD) was -35.79 kJ/mol, ΔE(6R,2'S)-diastereomer /(PIP-β-CD) was -46.15, and ΔΔE was 10.36 kJ/mol. For model II, ΔE levo-folinic acid /(P-β-CD) was -31.98 kJ/mol, ΔE(6R,2'S)-diastereomer /(PIP-β-CD) was -42.02, and ΔΔE was 10.04 kJ/mol. On account of the principle that the more negative the binding energy is, the stronger interaction takes place between the host and guest molecules and the more stable is the corresponding host-guest complex. Therefore, compared with the wide and narrow sides by which guest molecules entered from the cavity, it conforms that the complexation energies are in favor of model I. According to the energy values of each stereoisomers cyclodextrin complex, the order of stability of two folinic acid diastereomers was (6R,2'S)-diastereomer > levo-folinic acid indicating (6R,2'S)-diastereomer had a stronger interation with PIP-β-CD, which was consistent with the peak order in the previous experiments (Fig. 2). The optimized geometries for the lowest energy conformation for the inclusion complexes of two folinic acid diastereomers with PIP-β-CD are presented in Fig. 3A and 3B.


Separation of folinic acid diastereomers in capillary electrophoresis using a new cationic β-cyclodextrin derivative.

Yu J, Liang X, Wang Z, Guo X, Sun T, Guo X - PLoS ONE (2015)

The optimized geometries for the lowest energy conformation for the inclusion complexes of folinic acid diastereomers with PIP-β-CD.(A) levo-folinic acid with PIP-β-CD. (B) (6R,2'S)-diastereomer with PIP-β-CD. The molecular electrostatic potential (MEP) maps of the optimized conformation for the inclusion complexes of folinic acid diastereomers with PIP-β-CD. (C) levo-folinic acid with PIP-β-CD. (D) (6R,2'S)-diastereomer with PIP-β-CD.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4364531&req=5

pone.0120216.g003: The optimized geometries for the lowest energy conformation for the inclusion complexes of folinic acid diastereomers with PIP-β-CD.(A) levo-folinic acid with PIP-β-CD. (B) (6R,2'S)-diastereomer with PIP-β-CD. The molecular electrostatic potential (MEP) maps of the optimized conformation for the inclusion complexes of folinic acid diastereomers with PIP-β-CD. (C) levo-folinic acid with PIP-β-CD. (D) (6R,2'S)-diastereomer with PIP-β-CD.
Mentions: Firstly, using the optimized structures above, the semi-empirical PM3 method [12] was applied to search for the most stable inclusion complexation of folinic acid diastereomers into PIP-β-CD cavity from its wide (Model I) and narrow (Model II) sides by scanning the coordinate Z, from -8A to 8 A intervals. The calculated binding energies (ΔE) associated with the formation complexes of folinic acid diastereomer with PIP-β-CD are obtained using following equation: ΔE = Ecomplex − (Efree-guest + Efree-host), where Ecomplex, Efree-guest, Efree-host are the energies of complexes of folinic acid diastereomer with PIP-β-CD, free folinic acid diastereomer and free PIP-β-CD, respectively. The difference of ΔE of each isomer with PIP-β-CD is calculated using following equation: ΔΔE = ΔElevo-folinic acid /(PIP-β-CD) − ΔE(6R,2'S)-diastereomer /(PIP-β-CD), where ΔElevo-folinic acid /(PIP-β-CD) means the calculated binding energies of complexes of levo-folinic acid with PIP-β-CD, and ΔE(6R,2'S)-diastereomer /(PIP-β-CD) means the calculated binding energies of complexes of (6R,2'S)-diastereomer with PIP-β-CD. For model I, ΔElevo-folinic acid /(PIP-β-CD) was -35.79 kJ/mol, ΔE(6R,2'S)-diastereomer /(PIP-β-CD) was -46.15, and ΔΔE was 10.36 kJ/mol. For model II, ΔE levo-folinic acid /(P-β-CD) was -31.98 kJ/mol, ΔE(6R,2'S)-diastereomer /(PIP-β-CD) was -42.02, and ΔΔE was 10.04 kJ/mol. On account of the principle that the more negative the binding energy is, the stronger interaction takes place between the host and guest molecules and the more stable is the corresponding host-guest complex. Therefore, compared with the wide and narrow sides by which guest molecules entered from the cavity, it conforms that the complexation energies are in favor of model I. According to the energy values of each stereoisomers cyclodextrin complex, the order of stability of two folinic acid diastereomers was (6R,2'S)-diastereomer > levo-folinic acid indicating (6R,2'S)-diastereomer had a stronger interation with PIP-β-CD, which was consistent with the peak order in the previous experiments (Fig. 2). The optimized geometries for the lowest energy conformation for the inclusion complexes of two folinic acid diastereomers with PIP-β-CD are presented in Fig. 3A and 3B.

Bottom Line: The effect of background electrolyte pH, the concentration of the cyclodextrin additive, and organic modifier on the separation was investigated.A good separation of folinic acid diastereomers was obtained with 30 mmol/L phosphate buffer at pH 6.50 containing 6.0 mmol/L of mono-6-deoxy-6-piperdine-β-cyclodextrin in 10% acetonitrile.Moreover, a computational modeling study, using the semi-empirical PM3 method, was used to discuss the possible mechanism of separation of folinic acid with mono-6-deoxy-6-piperdine-β-cyclodextrin.

View Article: PubMed Central - PubMed

Affiliation: Department of Pharmaceutical Analysis, School of Pharmacy, Shenyang Pharmaceutical University, Ministry of Education, Shenyang, Liaoning Province, P. R. China.

ABSTRACT
A method for the separation of folinic acid diastereomers by capillary electrophoresis in chiral separation media was developed. Aiming to achieve a good separation of the anionic analytes, a newly synthesized cationic β-cyclodextrin derivative, mono-6-deoxy-6-piperdine-β-cyclodextrin, was applied as the chiral selector. The effect of background electrolyte pH, the concentration of the cyclodextrin additive, and organic modifier on the separation was investigated. A good separation of folinic acid diastereomers was obtained with 30 mmol/L phosphate buffer at pH 6.50 containing 6.0 mmol/L of mono-6-deoxy-6-piperdine-β-cyclodextrin in 10% acetonitrile. Based on the capillary electrophoresis data, the binding constants of each diastereomer with mono-6-deoxy-6-piperdine-β-cyclodextrin were determined. Moreover, a computational modeling study, using the semi-empirical PM3 method, was used to discuss the possible mechanism of separation of folinic acid with mono-6-deoxy-6-piperdine-β-cyclodextrin.

No MeSH data available.


Related in: MedlinePlus