PREDICTION OF GC ELUTION ORDER OF CHIRAL ORGANIC COMPOUNDS (DIASTEREOMERS AND ENANTIOMERS) BY MOLECULAR DYNAMICS MODELING

 

Igor G. Zenkevich1 and Rafael R. Kostikov2

1 Chemical Research Institute, 2 Chemical Department, St. Petersburg State University,

Universitetsky pr., 26, St. Petersburg 198504, Russia

Emails: Igor@IZ6246.spb.edu; rkost@RK1198.spb.edu

Prediction of relative order of GC elution of isomeric organic compounds is a useful method of identification, because their mass spectra are similar to each other. The results are based on computer evaluation of intramolecular vibration and rotational energies (E, kcal/mol) using molecular dynamics methods (HyperChem software). The existence of linear dependence between GC retention indices (RI) and these energies have been shown previously:

                        RI  »  a E + b    (a < 0)                        (1)

The negative sign of coefficient “a” means that isomers with larger E-values have smaller retention parameters and boiling points, correspondingly.

Earlier this approach has been successfully applied in identification of structural isomers of various series. However, another problem of high importance is the prediction of GC elution order of organic compounds with two or more chiral centers in the molecule having non-equal retention parameters on non-chiral stationary phases. In accordance with regularity (1) the less E-values for threo- (rac-) diastereomers comparing with these parameters for erythro- (meso-) forms mean the following sequence of their GC elution:

erythro- (meso-)  <  threo- (rac-).

This feature seems as a general rule and it is in good accordance with known reference data on boiling points and GC retention indices of individually characterized diastereomers. The next Table show a comparison of boiling points (Tb) and intramolecular dynamics parameters (E) of some diastereomers

Diastereomers

meso-  or   erythro-

rac-  or   threo-

Tb, ˚C

E (300 K)

Tb, ˚C

E (300 K)

2,3-Butanediol

181.7

34.7 ± 0.6

182.5

34.3 ± 0.6

Butanedioic acid, 2,3-diMe, diEt ester

218

64.0 ± 1.2

221-222

63.4 ± 1.1

2,3-Butanedithiol, S,S¢-diMe ether

108

49.3 ± 0.8

109-111

48.7 ± 0.8

2-Butanol, 3-chloro-

130.8-132

32.3 ± 0.5

135.4-136

31.8 ± 0.5

Pentane, 2,3-dichloro-

138-139

37.3 ± 0.6

143-144

37.0 ± 0.7

Butane, 2,3-dichloro-

112-116.7

30.0 ± 0.4

116-117.5

29.8 ± 0.4

Butane, 2,3-dibromo-

157.3-159

28.9 ± 0.4

160.5-161.5

28.6 ± 0.4

Next problem is the prediction of elution order of enantiomers on chiral phases (namely, cyclodextrines). Any modeling of chromatographic interaction of enantiomers with these phases seems impossible. However, it can be fulfilled by their hypothetical treatment by specially selected computer derivatization reagents containing extra chiral centers (*) in the molecules. It is equivalent to the conversion of enantiomers into diastereomers considered above. Namely, to predict the elution of enantiomeric alcohols RR¢R¢¢C*OH their “conversion” into diastereomeric sterically hindered phosphine oxides [the “reagent” is HP*O(CH3)-C(CH3)3] or other similar derivatives can be recommended:

RR¢R¢¢C*OH   ®   RR¢R¢¢C*-P*O(CH3)-C(CH3)3

For example, the higher E-value for this derivative of (R)-linalool comparing with (S)-enantiomer confirms its smaller retention parameters on b-cyclodextrine (Restek Product Guide; 1999, P. 462).