Enantiodiscrimination by a quinine-based chiral stationary phase: A computational study

Chirality

Volumn 12, Issue 1, 2000, Pages 7-15

  Schefzick, Sabine ^a   Lindner, Wolfgang ^a   Lipkowitz, Kenny B ^b   Jalaie, Mehran ^b  

^a UNIVERSITY OF VIENNA   (Austria)

^b INDIANA UNIVERSITY   (United States)

Author keywords

Chiral stationary phase; Chirality; Computational chemistry; Enantiodiscrimination; Molecular dynamics; Molecular modeling

Indexed keywords

CARBAMIC ACID; LEUCINE; NITROBENZENE DERIVATIVE; QUININE; QUINOLINE; QUINUCLIDINE;

ARTICLE; BINDING SITE; CHEMICAL STRUCTURE; CHIRALITY; COMPLEX FORMATION; ENANTIOMER; ENERGY; FORCE; MOLECULAR DYNAMICS; MOLECULAR INTERACTION; MOLECULAR RECOGNITION; PRIORITY JOURNAL;

BINDING SITES; COMPUTER SIMULATION; ELECTROSTATICS; MODELS, CHEMICAL; MODELS, MOLECULAR; MOLECULAR CONFORMATION; QUININE; STEREOISOMERISM; STOCHASTIC PROCESSES; THERMODYNAMICS;

EID: 0033962554     PISSN: 08990042     EISSN: None     Source Type: Journal    
DOI: 10.1002/(SICI)1520-636X(2000)12:1<7::AID-CHIR3>3.0.CO;2-Q     Document Type: Article

References (31)

1. Lämmerhofer M, Lindner W. Quinine and quinidine derivatives as chiral selectors. Brush type chiral stationary phases for high-performance liquid chromatography based on cinchonan carbamates and their application as chiral anion exchangers. J Chromatogr A 1996; 741:33-48.
2. Lämmerhofer M, Maier N, Lindner W. Chiral anion exchange type stationary phases based on chinchonan alkaloids: effective tool for the separation of the enantiomers of chiral acids. Am Lab 1998;30:71-78.
3. Lämmerhofer M, Lindner W. High-efficiency chiral separations of N-derivatized amino acids by packed-capillary electrochromatography with a quinine based chiral anion exchange type stationary phase. J Chromtogr A 1998;829:115-125.
4. a) Rosini C, Bertucci C, Pini D, Altemura P, Salvadori P. Chiral stationary phase based on cinchona alkaloids for the HPLC resolution of racemates. Chromatographia 1987;24:671-676.
5. b) Salvadori P, Rosini C, Pini D, Bertucci C, Altemura P, Uccello-Barretta G, Raffaelli A. A novel application of cinchona alkaloids as chiral auxiliaries: preparation and use of new chiral stationary phases for the Chromatographic resolution of racemates. Tetrahedron 1987;43:4969-4978.
6. c) Rosini C, Bertucci C, Pini D, Altemura P, Salvadori P. Cinchona alkaloids for preparing new, easily accessible chiral stationary phases. I. Tetrahedron Lett 1985;26:3361-3364.
7. d) Rosini C, Altemura P, Pini D, Bertucci C, Zullino G, Salvadori P. Cinchona alkaloids for preparing new, easily accessible chiral stationary phases. II. J Chromatogr 1985;348:79.
8. e) Salvadori P, Pini D, Rosini C, Bertucci C, Uccello-Barretta G. Chiral discriminations with cinchona alkaloids. Chirality 1992;4:43.
9. Lesnik J, Lämmerhofer M, Lindner W. FT-IR characterization of complexes of carbamoylated quinidine chiral selectors and N-derivatized leucine enantiomers in solution: evidence for stereoselective intermolecular interaction events. Anal Chim Acta 1999 (in press).
10. Lämmerhofer M, Di Eugenio P, Molnar I, Lindner W. Computerized optimization of the high-performance liquid Chromatographic enantioseparation of a mixture of dinitrophenyl amino acids on a quinine carbamate-type chiral stationary phase using drylab. J Chromatogr B Biomed Sci Appl 1997;689:123-135.
11. Lämmerhofer M, Lindner W. High-efficiency enantioseparations of N-derivatized amino acids by packed capillary electrochromatography (CEC) using ODS silica and a quinine derived chiral selector as a ion-pair agent. J Chromatogr A 1999;839:167-182.
12. Kleidernigg OP, Lämmerhofer M, Lindner W. Determination of the enatiomeric excess of (R)-and (S)-proline using a new indirect and direct chiral separation technique by HPLC: method development and evaluation of accuracy. Enantiomer 1996;1:387-402.
13. Mandl A, Nicoletti L, Lämmerhofer M, Lindner W. Quinine versus carbamoylated quinine derivate type chiral stationary phases: a comparison regarding their enantioselectivity for the HPLC-enantioseparation of N-derivatized primary and secondary amino acids. J Chromatogr A 1999 (in press).
14. Piette V, Lämmerhofer M, Lindner W, Crommen J. Enantiomeric separation of N-protected amino acids by non-aqueous capillary electrophoresis using tert-butyl carbamoylated quinine as chiral additive. Chirality 1999;11:622-630.
15. Mohamadi F, Richards NGJ, Guida WC, Liskamp R, Lipton M, Caufield C, Chang G, Hendrickson T, Still WC. MacroModel - an integrated software system for modeling organic and bioinorganic molecules using molecular mechanics. J Comput Chem 1990;11:440-467.
16. Still WC, Tempczyk A, Hawley RC, Hendrickson T, Semianalytical treatment of solvation for molecular mechanics and dynamics. J Am Chem Soc 1990;112:6127-6129.
17. Leach A. A survey of methods for searching the conformational space of small and medium-sized molecules. In: Lipkowitz KB, Boyd DB, editors. Reviews in computational chemistry, vol 2. New York: VCH: 1991. p 1-47.
18. Peterson MA. Understanding enantiodifferentiation through molecular simulations. PhD Thesis, Purdue University; 1996. p 15.
19. IRIS Explorer Center (North America), Downers Grove, IL 60551-65702 or via URL http://www.nag.co.uk/lh/Welcome IEC.
20. Lipkowitz KB. Atomistic modeling of enantioselective binding. Acc Chem Res 1999, submitted.
21. Däppen R, Karfunkel HR, Leusen FJJ. Computational chemistry applied to the design of chiral stationary phases for enantiomer separation. J Comput Chem 1990;11:181-193.
22. A reviewer expresses the concern that it is too restrictive to consider only the global minima in the docking process when significantly populated conformers are concerned. In our earlier work (Ref. 16), the computational strategy we implemented did indeed use multiple conformers in the docking process. However, the working assumption here is that by using very long simulation times the individual molecules in each binary complex would undergo conformational transitions (this was found, see text) and accordingly, beginning on different locations of the PES by docking different conformers is not warranted. The results of our simulations agree with experimental separation factors, thus validating our approximation.
23. Leach AR. Molecular modeling - principles and applications. Edinburgh: Addison Wesley Longman; 1996. p 347-351.
24. Lipkowitz KB, Pearl G, Coner B, Peterson MA. Explanation of where and how enantioselective binding takes place on a permethyated β-cyclodextrin, a chiral stationary phase used in gas chromatography. J Am Chem Soc 1997;119:600-610.
25. Dijkstra GDH, Kellogg RM, Wynberg H, Svendsen JS, Mark I, Sharpless KB. Conformational study of cinchona alkaloids. A combined NMR, molecular mechanics, and X-ray approach. J Am Chem Soc 1989;111:8069-8076.
26. Dijkstra GDH, Kellogg RM, Wynberg H. Conformational study of cinchona alkaloids. A combined NMR and molecular orbital approach. J Org Chem 1990;55:6121-6131.
27. Michael Laemmerhofer. Unpublished results. University of Vienna.
28. Lipkowitz KB. Symmetry breaking in cyclodextrins: a molecular mechanics investigation. J Org Chem 1991;56:6357-6367.
29. Lipkowitz KB. Applications of computational chemistry to the study of cyclodextrins. Chem Rev 1998;98:1829-1873.
30. Lipkowitz KB, Coner R, Peterson MA. Locating regions of maximum chiral discrimination: a computational study of enantioselection on a popular chiral stationary phase used in chromatography. J Am Chem Soc 1997;119:11269-11276.
31. Lipkowitz KB, Coner R, Peterson MA, Morreale A, Shackelford JA. The principle of maximum chiral discrimination: chiral recognition in permethyl-β-cyclodextrin. J Org Chem 1998;63:732-745.