Summary
Quantitative structure-enantiospecific retention relation-ships (QSERR) have been derived for a series of 1,4-benzodiazepines. The compounds were chromatographed on a human serum albumin based HPLC chiral stationary phase (HSA-CSP). Molecular modeling of the solutes allowed the determiantion of various structural descriptors. Among these descriptors, a submolecular polarity parameter, PSM, was identified which was able to characterize enantiospecific interactions of benzodiazepines with the HSA-CSP. Combining PSM with the retention parameter of the less retained enantiomer permitted precise prediction of the retention of the second eluting enantiomer. Highly statistically significant regression equations were also derived which described the retentions of both enantiomers in terms of nonempirical molecular descriptors. The calculated enantioselectivity correlated well with the experimentally observed values. A significant conclusion from this study is support for the existence of two different binding sites for chiral benzodiazepines on HSA.
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References
R. Kaliszan, “Quantitative Structure-Chromatographic Retention Relationships”, John Wiley & Sons, New York, 1987, p. 3.
U. Norinder, J. Hermansson, Chirality3, 422 (1991).
T. A. G. Noctor, C. D. Cuong, I. W. Wainer, in preparation.
E. Domenici, C. Bertucci, P. Salvadori, G. Felix, I. Cahagne, S. Motellier, I. W. Wainer, Chromatographia29, 170 (1990).
E. Domenici, C. Bertucci, P. Salvadori, S. Motellier, I. W. Wainer, Chirality2, 263 (1990).
E. Domenici, C. Bertucci, P. Salvadori, I. W. Wainer, J. Pharm. Sci.80, 164 (1991).
T. A. G. Noctor, D. S. Hage, I. W. Wainer, J. Chromatogr in press (1992).
T. A. G. Noctor, I. W. Wainer, Pharm. Res.9, 480 (1992).
A. J. Leo, in “Comprehensive Medical Chemistry”, Vol. 4,C. Hansch, P. G. Sammes, J. B. Taylor, eds., Pergamon, Oxford, 1990; p. 295.
P. N. Craig, in “Comprehensive Medicinal Chemistry”, Vol. 6,C. Hansch, P. G. Sammes, J. Taylor, eds., Pergamon, Oxford, 1990; p. 237.
M. J. S. Dewar, W. Thiel, J. Amer. Chem. Soc.99, 4899 (1977).
M. J. S. Dewar, H. S. Rzepa, J. Comp. Chem.4, 158 (1983).
M. Charton, S. Clementi, S. Ehrenson, O. Exner, J. Shorter, S. Wold, Quant. Struct. Act. Relat.4, 29 (1985).
I. Fitos, J. Visy, A. Magyar, J. Kajtar, M. Simonyi, Chirality2, 161 (1990).
B. L. Karger, L. R. Snyder, E. Eon, J. Chromatogr.125, 71 (1976).
R. Kaliszan, K. Osmialowski, S. A. Tomellini, S.-H. Hsu, S. D. Fazio, R. A. Hartwick, Chromatographia20, 705 (1985).
R. W. Lucek, C. B. Coutinho, Mol. Pharmacol.12, 612 (1976).
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Kaliszan, R., Noctor, T.A.G. & Wainer, I.W. Quantitative structure-enationselective retention relationships for the chromatography of 1,4-benzodiazepines on a human serum albumin based HPLC chiral stationary phase: An approach to the computational prediction of retention and enantioselectivity. Chromatographia 33, 546–550 (1992). https://doi.org/10.1007/BF02262246
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DOI: https://doi.org/10.1007/BF02262246