Re: QSAR - new question on chirality descriptors

Dear Francisco Torrens,

CIP descriptors were designed for labelling and specifying stereogenic
units, and problems should be expected when they are applied to
structure-property relationships. It is common that compounds belonging
to the same stereochemical 'family' have different CIP descriptors due
to artifacts of CIP rules.

Optical properties at least have a physical meaning, although their
relationship with structure is in general quite difficult to model.

Structure-based chirality descriptors derived from physicochemical
properties (like charges or polarizabilities) should be more appropriate
for QSAR. Our recent work on the development of such descriptors is
reported in

J. Aires-de-Sousa, J. Gasteiger, "A New Description of Molecular
Chirality and its Application to the Prediction of the Preferred
Enantiomer in Stereoselective Reactions", J. Chem. Inf. Comp. Sci.,
2001, 41 (2), 369-375.

J. Aires-de-Sousa, J. Gasteiger, “Prediction of enantiomeric selectivity
in chromatography. Application of conformation-dependent and
conformation-independent descriptors of molecular chirality”, J. Molec.
Graphics and Model. 2002, 20 (5), 373-388.

Different approaches (some incorporating CIP descriptors into known
topological descriptors) are:

1. D. Avnir, H. Z. Hel-Or, P. G. Mezey, Symmetry and Chirality:
Continuous Measures. In The Encyclopedia of Computational Chemistry;
Schleyer, P. v. R., Allinger, N. L., Clark, T., Gasteiger, J., Kollman,
P. A., Schaefer III, H. F., Schreiner, P. R., Eds.; John Wiley & Sons:
Chichester, 1998; Vol. 4, pp. 2890-2901. (and other papers of Avnir).

2. A. Seri-Levy, S. West, W.G. Richards, J. Med. Chem. 1994, 37, 1727.

3. I. Lukovits, W. Linert, J. Chem. Inf. Comp. Sci., 2001, 41, 1517-1520.

4. R. Benigni, M. Cotta-Ramusino, G. Gallo, F. Giorgi, A. Giuliani, M.R.
Vari, J. Med. Chem. 2000, 43, 3699-3703.

5. J. V. Julián-Ortiz, C. G. Alapont, I. Ríos-Santamarina, R.
García-Doménech, J. Gálvez, J. Molec. Graph. Model. 1998, 16, 14-18.

6. A. Golbraikh, D. Bonchev, A. Tropsha, J. Chem. Inf. Comput. Sci.
2001, 41, 147-158.

7. J. S. Mason, I. Morize, P. R. Menard, D. L. Cheney, C. Hulme, R. F.
Labaudiniere, J. Med. Chem.1999, 42, 3251-3264.

8. Scott A. Wildman and Gordon M. Crippen, J. Chem. Inf. Comput. Sci.
2003, 43, 629-636. Scott A. Wildman and Gordon M. Crippen. J. Mol.
Graphics Modell. 21 (2002) 161–170.

Recent reviews (at different levels) on the topic of chirality
descriptors are:
a) J. Aires-de-Sousa, "Chirality Descriptors", in Chemoinformatics - A
Textbook, eds. Johnann Gasteiger and Thomas Engel, Wiley-VCH, 2003, 418-427;
b) J. Aires-de-Sousa, "Representation of Molecular Chirality", in
Handbook of Chemoinformatics, ed. Johnann Gasteiger, Wiley-VCH, 2003,
1062-1078.

Best regards,
Joao Aires de Sousa

-- 
Dr. Joao Aires de Sousa
Departamento de Quimica, Faculdade de Ciencias e Tecnologia,
Universidade Nova de Lisboa, 2829-516 Caparica, Portugal
Tel: (+351) 21 2948300 x10986   Fax: (+351) 21 2948550
Email: jas**fct.unl.pt
www: http://www.dq.fct.unl.pt/staff/jas/
Francisco Torrens wrote:
> NB: Unless you reset the To: line, your reply goes to the entire list
> ---
> 
> Dear,
>   I should appreciate if you answer me the following question:
>   In order to do a QSAR on chiral compounds (e.g. barbiturates) and to
> include chirality, which chiral descriptor seems more interesting:
>   a) experimental (+)/(-) deviation of the polarization plane, or
>   b) "geometric" (R)/(S) IUPAC (Cahn-Ingold-Prelog) structure?
>   Thank you for your attention,
>                 yours sincerely,
>