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![Page 1: Chiralm selective chromatography D. Kozma ed. Handbook of Optical Resolutions via Diastereomeric Salt Formation. CRC Handbooks, 2001. Z Juvancz, G. Seres.](https://reader035.fdocuments.in/reader035/viewer/2022062803/56649f255503460f94c3c6bd/html5/thumbnails/1.jpg)
Chiralm selective chromatography
D. Kozma ed. Handbook of Optical Resolutions via Diastereomeric Salt Formation. CRC Handbooks, 2001.Z Juvancz, G. Seres Appendix
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Definition of chirality
• Chiral molecules are asymmetric.
• Enantiomers or optical isomers are mirror image of each others, but they are not same.
• Diastereomeric molecules are not
• mirror images, but they have same constitutions.
Central chirality with for different substituents.
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Enantiomers
Kajtár M., Változatok négy elemre, Gondolat, 1984.
DNS molecules
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Application of chiral selective analysis
Checking the chiral selective synthesis:Pharmaceutical, pesticide industry
Metabolite research: (pl. Warfarin, Ibuprofen, pheromonos)
Adulteration, bacterial infectiouns: ( pl. wine, essential oils)
Racemisation: (pl. heat treatment, age determination)
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Different effects of enantiomeric pharmaceuticals
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Share of enantiomeric pure pharmceuticals
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Different odor of enatiomers
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Three point interaction is necessary for the chiral recognation I.
V.R. Meyer, M. Rais,Chirality1 (1989) 167.
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Two point interactions are not enough II.
V.R. Meyer, M. Rais, Chirality 1 (1989) 167.
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Certain rigidity is necessary for chiral recognition
V.R. Meyer, M. Rais,Chirality1 (1989) 167.
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Interaction points can be surface or axis
π acid - π base, and h_bridge are the key interactions.
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Working theory of chiral stationer phase, (CSP)
C. Welch et al., Review of Stereochemistry
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Working theory of chiral mobile phase addtitive (CMA)
C. Welch et al., Review of Stereochemistry
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General rules of chiral selective chromatography
• Rigid structure offers high selectivity.• Flexible structure offer broad selectivity range.• Most of the separation bases on three point
interaction.• Functional groups close to asymmetric center
improves the resolution.• Repulsion interactions have a big role.• Low analysis temperature improves the separations.
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Temeperature dependence of chiral chromatography
ln α = S+- (S0sm)/R - H+- (H0
sm)/RT +- : difference between the two isomers (+and -)
sm: difference between two phases (stationary and mobile).
Generally the low analysis temperature improve the separation.
Using high efficiency stationary phase, 0,1kJ/mol (α: 1,01) energy difference is enough between the enantiomers for Rs 1.5 resolution value.
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Importance of minor first elution order
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Most frequently used CSP are cyclodextrin based molecules
.
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Shape of derivatized a CD
The direction and length of bonds are differents..
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Reason of good chiral recognation properties of cyclodextrins
• There are several chiral center in a CD
• The surrounding of chiral centers are of uniform in a glucose unit.
• The shape of glucose units are different
• Substituted derivates are bunch of isomers
• The chiral recognition depends on the type of substituents
• The selectivity can depend on the ionized state
• Cyclodextrins have flexible structure (induce fit)
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Cyclodextrins can separate even the functionless hydrocarbons enantiomers
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Selecticvity vs. Concetration of chiral selector
The acharial silicone matrix offers a good efficiency.
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Selecticvity vs. Concetration of chiral selector
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Low analysis temperature results in high selectivity
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Cyclic derivatives give high selectivity
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Separation of enetiomers of essential aminoacids with Chirasil-Val
Orginal CSP ImprovedCSP
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Chiral selective HPLC
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Most frequently used CSps in
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Key interaction of polysaccharide CSps
H-bridge ands π- π interactions
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Selectivity depend on the substitution of cellulose
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Cyclodextrin CSp in HPLC
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Cyclodextris as CMAs (
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Methylated cyclodexrin CMAs
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Pirkle type CSP
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Separation with π base CSP
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Vancomycin, antibiotic CSP
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Separation with Vancomycin CSP
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Chiral separation in CE
Neutral selector can not separate neutral molecules.The oppositely charged selector and sample offer high resolution.Separation has maximum value in the function of the selector concentration.
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Separation vs. concentration of selector
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High selectivity with oppositelly charged sample and selector
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Used chiral selectors in CE
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Separations of pyretroic acids
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Chiral separation with β-HDMACD
0,5 mMol concentration of selectror is enough for baseline separation.
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Chiral selective separation of
γ-PhoCD reversed migration orders TRIMEB
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Dual CD seletor system
min2 4 6 8 10 12 14
mAU
-20
-10
0
10
20
30
min2 4 6 8 10 12 14
mAU
-20
-10
0
10
20
30
min2 4 6 8 10 12 14
mAU
-20
-10
0
10
20
30
min 5 10 15 20 25
mAU
-10 -5 0 5
10 15 20
50 mM acetic acid / TRIS; pH 5.0
+ 1 mM MACD50 mM acetic acid / TRIS; pH 5.0
50 mM acetic acid / TRIS; pH 5.0
+ 10 mM PMMACD
50 mM acetic acid / TRIS; pH 5.0 + 1 mM MACD + 10 mM PMMACD
Kass : 100 – 370 M-1
Kass : 1.3 – 70 M-1
mecoprop, 2,4-DP, 3ClPPA
Fenoprop
4MePPA
PPA
R. Iványi et al.
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The selectivity of ionizable CDs depend on their ionized states
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Partially filling technique
No EOF (acrylamide coated column).The sample and selector migrate in opposite directions.The selector nigrates away, when the sample reaches the detector windows.
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Vancomicine selector
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Chiral selector with chiral MKEC agent
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Chips chiral separation
Designed for Martian space rockett
EKC
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Chiral CEC
Monolit CSP selector